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    You are here : Home » MS Research News » Drugs » Trimesta (Oral Estriol)

    Trimesta (Oral Estriol)

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    About TRIMESTA

    Trimesta is an orally active, immunomodulatory and anti-inflammatory molecule which has been approved and marketed throughout Europe and Asia for approximately 40 years for the treatment of post-menopausal hot flashes, but which has never been introduced in North America. Estriol, the active ingredient in Trimesta, is a weak estrogenic-based molecule that is produced in the placenta by women during pregnancy. Estriol is considered to play an important role in the immunologic privilege offered to the fetus during pregnancy, and is also thought to be responsible for the spontaneous remission of Th1-mediated autoimmune diseases of women (such as multiple sclerosis and rheumatoid arthritis) during pregnancy, especially during the third trimester. Adeona has an exclusive worldwide license from UCLA to issued and pending patents invented by Dr. Voskuhl including U.S. Patent 6,936,599 covering estriol's use for MS

    Completion of enrollment in 164 patient clinical trial of oral Trimesta(TM) for MS
    Synthetic Biologics LogoSynthetic Biologics, Inc. announced today that patient enrollment has been completed in a Phase II clinical trial evaluating the efficacy and safety of Synthetic Biologics' proprietary oral formulation of estriol (Trimesta(TM)) for the treatment of relapsing-remitting multiple sclerosis (MS). With over $8 million in external grant funding awarded to date, this Trimesta clinical trial should be fully funded to its completion.

    "The completion of patient enrollment into the Phase II Trimesta trial represents another important milestone for oral estriol and brings us one step closer to offering a new oral treatment option to patients with relapsing-remitting MS," said Jeffrey Riley, Chief Executive Officer of Synthetic Biologics. "As an oral therapy with a promising clinical profile, Trimesta is expected to be extremely well positioned to provide an important treatment option for this debilitating disease."

    The randomized, double-blind, placebo-controlled, multi-center Phase II clinical trial of Trimesta (oral estriol) for relapsing-remitting MS in women initially enrolled a total of 164 patients. At 15 sites in the United States, clinical investigators have been administering either oral Trimesta or matching placebo in addition to glatiramer acetate (Copaxone®), an FDA-approved therapy for MS, to women between the ages of 18-50 who have been recently diagnosed with relapsing-remitting MS. MS patients are being dosed and monitored for two years.

    The primary outcome measure for the study is the rate of relapse between the placebo and treated groups at two years, an accepted FDA-approvable endpoint in MS. Additional information regarding the relapsing-remitting MS clinical trial is available at http://www.clinicaltrials.gov/ct2/show/NCT00451204 .

    Current sales of injectable disease-modifying therapies for MS are estimated at $8.9 billion annually. According to various reports, sales of oral disease-modifying therapies for MS, of which Trimesta(TM) if and when approved would be in such class, are anticipated to exceed $5 billion annually by 2017.

    "We are pleased to complete the enrollment of a total of 164 patients in this landmark MS trial," said Rhonda Voskuhl, M.D., Director, University of California, Los Angeles (UCLA) Multiple Sclerosis Program, UCLA Department of Neurology, and lead Principal Investigator of the trial. "In the United States alone, over 200 people per week are diagnosed with MS, and approximately 70% of them are women. Typically, relapsing-remitting MS is distinguished from the other forms of MS by the relapses, or attacks of declining neurologic function, followed by periods of remission. With this trial evaluating oral estriol (Trimesta), we would expect to demonstrate a reduction in the rate of relapses in these MS patients."

    About Trimesta (oral estriol)

    Trimesta is Synthetic Biologics' proprietary drug candidate for the treatment of relapsing-remitting MS in women. Estriol has been approved and marketed for over 40 years throughout Europe and Asia for the treatment of post-menopausal hot flashes. It has never been approved by the FDA for any indication in the United States.

    It has been scientifically documented that pregnant women with certain autoimmune diseases experience a spontaneous reduction of disease symptoms during pregnancy, particularly in the third trimester. The PRIMS (Pregnancy In Multiple Sclerosis) study, a landmark clinical study published in the New England Journal of Medicine followed 254 women with MS during 269 pregnancies, and for up to one year after delivery. The PRIMS study demonstrated that relapse rates were significantly reduced by 71 percent (p < 0.001) through the third trimester of pregnancy compared to pre-pregnancy-rates, and that relapse rates increased by 120 percent (p < 0.001) during the first three months after birth (post-partum) before returning to pre-pregnancy rates.

    It has been hypothesized that the female hormone, estriol, produced by the placenta during pregnancy, plays a role in "fetal immune privilege," a process that prevents a mother's immune system from attacking and rejecting her fetus. Maternal levels of estriol increase in a linear fashion through the third trimester of pregnancy until birth, whereupon they abruptly return to low circulating levels. The anti-autoimmune effects of estriol may also be responsible for the beneficial effects of pregnancy on MS.

    Rhonda Voskuhl, M.D., has found that levels of estriol equivalent to pregnancy have potent immunomodulatory effects on MS. Dr. Voskuhl has further shown in a small number of non-pregnant female MS patients that estriol may have a therapeutic benefit by regulating the immune system and thus reducing the relapse rates, similar to the response seen in MS patients during pregnancy.

    Source: PR Newswire Copyright (C) 2012 PR Newswire (14/03/12)

    Adeona commences multiple sclerosis drug Trimesta trial

    Adeona LogoAdeona Pharmaceuticals has begun the Phase II study of its Trimesta drug, used for the treatment of cognitive dysfunction in multiple sclerosis (MS).

    Trimesta is an oral estriol designed for treating relapsing-remitting MS and for cognitive dysfunction in MS, both in female patients, and has been approved throughout Europe and Asia to treat post-menopausal symptoms.

    The Phase II trial is a randomized double-blind placebo-controlled study expected to enroll 64 relapsing-remitting or secondary-progressive female MS patients.

    In the study, the primary objective is the average change in Paced Auditory Serial Addition Test (PASAT) scores at 12 months between each group, and secondary endpoints include relapse rates, whole brain atrophy determined by MRI and safety.

    Principal investigator of the study Rhonda Voskuhl said the aim of this trial is to address the unmet need for MS patients, improving a person's mental sharpness and ability to continue working.

    Currently, another 15-center Phase II randomized double-blind placebo-controlled clinical trial is underway, intended to demonstrate Trimesta's ability to reduce relapse rates in women with the relapsing-remitting form of MS.

    Source: PBR © PBR 2012 (20/01/12)

    Adeona and the Skirball Foundation join forces to advance MS Research

    Adeona LogoAdeona Pharmaceuticals, Inc. announced that the Company's drug candidate, Trimesta™ (oral estriol), will be utilized in a new Phase II clinical trial to evaluate its potential therapeutic effect on cognitive dysfunction observed in female multiple sclerosis (MS) patients.

    The Skirball Foundation and Adeona have pledged to equally support this clinical trial led by Rhonda Voskuhl, M.D., Director, University of California, Los Angeles (UCLA) Multiple Sclerosis Program, Department of Neurology. The study, which focuses on cognition loss in MS patients, also received contributions from numerous supporters, such as the Sherak Family Fund, the Gustafson Fund, and the Diamont family.

    "At some point, 50-65 percent of MS patients will develop problems due to cognitive loss, yet there remains no treatment to target this profound disability. Unfortunately, loss of cognition affects a person's ability to work and is the major reason MS patients stop or decrease their level of work," said Dr. Voskuhl, Principal Investigator. "We are therefore thrilled to begin this novel clinical trial of Trimesta in which the primary endpoint is improvement in cognition and the ultimate goal is to address an unmet need for these patients."

    This new randomized, double-blind, placebo-controlled Phase II clinical trial is based on findings from a 10-patient, 22-month, single-agent, crossover clinical trial conducted by Dr. Voskuhl. The results from the crossover trial demonstrated a statistically significant 14% improvement from baseline in Paced Auditory Serial Addition Test (PASAT) cognitive testing scores (p = 0.04) in MS patients after six months of Trimesta therapy. PASAT is a routine cognitive test performed in patients with a wide variety of neuropsychological disorders such as MS.

    "We are very pleased to announce the initiation of this new clinical trial that will evaluate our drug candidate Trimesta," said James S. Kuo, M.D., M.B.A., Adeona's CEO and President. "Results from the ongoing Phase II relapsing-remitting MS clinical trial and this new Phase II clinical trial for cognitive dysfunction in MS patients should provide results within the same time frame.

    Expanding the clinical development of Trimesta in the United States to include cognitive benefit should broaden the potential treatment options for women suffering from MS and should increase the economic opportunity for our drug candidate."

    About Trimesta™ (oral estriol)

    Trimesta is Adeona's proprietary drug candidate for the treatment of relapsing-remitting MS and for cognitive dysfunction, both in female patients. Estriol has been approved and marketed for more than 40 years throughout Europe and Asia for the treatment of post-menopausal hot flashes. It has never been approved in the United States by the Food and Drug Administration (FDA) for any indication.

    On September 19, 2011, Adeona announced that the 150th patient has been enrolled in the randomized, double-blind, placebo-controlled, multi-center clinical trial of its Trimesta drug candidate for relapsing-remitting MS in women, per the original protocol. The Company also announced that Dr. Voskuhl had received funding to continue enrollment of an additional 10-20 patients at all 15 centers.

    About Cognitive Dysfunction in Multiple Sclerosis

    According to the National Multiple Sclerosis Society and the Multiple Sclerosis Society of Canada publication, Hold that Thought! Cognition and MS, it is fairly common for people with multiple sclerosis to complain of problems remembering things, finding the right words, concentrating on a task or something they are reading, or following a conversation. These are all cognitive symptoms of multiple sclerosis. Fifty to sixty-five percent of those affected by multiple sclerosis have cognitive dysfunction. Despite the fact that most symptoms are mild to moderate, they can have a significant impact on a person's ability to normally function. The overall cognitive dysfunction can be described as a reduction in mental "sharpness."

    The major areas of cognition that can be dysfunctional include what are termed complex attention and executive functions. Complex attention involves multitasking, the speed with which information can be processed, learning and memory, and perceptual skills; executive functions include problem solving, organizational skills, the ability to plan, and word finding. Just as the nature, frequency, and severity of multiple sclerosis-related physical problems can widely vary, not all people with multiple sclerosis will display these cognitive issues, and no two people will experience exactly the same types or severity of problems.

    About the Phase II Trimesta™ Clinical Trial for Cognitive Dysfunction in Multiple Sclerosis

    The randomized, double-blind, placebo-controlled clinical trial of Trimesta is expected to enroll 64 relapsing-remitting or secondary-progressive female MS patients at UCLA. Those between the ages of 18 and 50 will be randomized 1:1 into the treatment and placebo groups. Dr. Voskuhl will administer either oral Trimesta or a matching placebo, in addition to any FDA-approved standard MS treatment. Each patient will be dosed and monitored for one year after being enrolled. The primary endpoint is better cognition scores in the Trimesta group versus the placebo group based on PASAT cognitive testing scores.

    Source: Medical News Today © MediLexicon International Ltd 2004-2011 (13/11/11)

    Completion of planned enrollment in phase II MS trial of Trimesta™

    Adeona Pharmaceuticals LogoAdeona Pharmaceuticals, Inc. announced today that the 150th patient has been enrolled in the randomized, double-blind, placebo-controlled, multi-center clinical trial of its Trimesta™ (oral estriol) drug candidate for relapsing-remitting multiple sclerosis (MS) in women, per the original protocol.

    The Company also announced that Rhonda Voskuhl, M.D., Director, University of California, Los Angeles (UCLA) Multiple Sclerosis Program, UCLA Department of Neurology, and lead Principal Investigator of this Phase II clinical trial, has funding available to continue enrollment at all 15 centers, therefore, increasing the power of the trial. It is anticipated that the remaining grant funding will allow for the enrollment of an additional 10-20 patients.

    "We are excited to announce the enrollment of the 150th MS patient in this clinical trial, achieving our original targeted goal for enrollment. I am also very pleased that we have funds available to continue enrolling additional patients in this landmark MS trial," said Dr. Voskuhl. "Of the 400,000 people in the U.S. afflicted with MS, approximately 85% are initially diagnosed with relapsing-remitting MS, which is characterized by relapses, or attacks of declining neurologic function, followed by periods of remission. As we continue to dose and monitor each MS patient enrolled in the trial over a two year period, we would expect to demonstrate a statistically significant reduction in the rate of relapses in the patients treated with oral Trimesta."

    "Completing enrollment in the Trimesta MS clinical trial as originally prescribed in the protocol is a significant milestone for Adeona and for MS patients, as it brings us one step closer to a potential treatment for women suffering from this devastating disease," stated James S. Kuo, M.D., M.B.A., Adeona's Chairman and CEO. "Once all of the patients have been enrolled and dosed for two years, we look forward to announcing Dr. Voskuhl's top-line results, and if positive, we would expect to seek FDA guidance on filing a New Drug Application."

    About Trimesta (oral estriol)

    Trimesta (oral estriol) is Adeona's proprietary drug candidate for the treatment of relapsing-remitting MS in women. Estriol has been approved and marketed for over 40 years throughout Europe and Asia for the treatment of post-menopausal hot flashes. It has never been approved by the FDA for any indication in the United States.

    It has been scientifically documented that pregnant women with certain autoimmune diseases experience a spontaneous reduction of disease symptoms during pregnancy, particularly in the third trimester. The PRIMS (Pregnancy In Multiple Sclerosis) study, a landmark clinical study published in the New England Journal of Medicine followed 254 women with MS during 269 pregnancies, and for up to one year after delivery. The PRIMS study demonstrated that relapse rates were significantly reduced by 71 percent (p < 0.001) through the third trimester of pregnancy compared to pre-pregnancy-rates, and that relapse rates increased by 120 percent (p < 0.001) during the first three months after birth (post-partum) before returning to pre-pregnancy rates.

    It has been hypothesized that the female hormone, estriol, produced by the placenta during pregnancy, plays a role in "fetal immune privilege," a process that prevents a mother's immune system from attacking and rejecting her fetus. Maternal levels of estriol increase in a linear fashion through the third trimester of pregnancy until birth, whereupon they abruptly return to low circulating levels. The anti-autoimmune effects of estriol may also be responsible for the beneficial effects of pregnancy on MS.

    Rhonda Voskuhl, M.D., has found that levels of estriol equivalent to pregnancy have potent immunomodulatory effects on MS. She has further shown in a small number of non-pregnant female MS patients that estriol may have a therapeutic benefit by regulating the immune system and thus reducing the relapse rates, similar to the response seen in MS patients during pregnancy.

    About the Phase II Trimesta Clinical Trial for Relapsing-Remitting Multiple Sclerosis

    The randomized, double-blind, placebo-controlled clinical trial of Trimesta has enrolled the original target of 150 patients and will continue to enroll patients at 15 centers in the United States. Investigators are administering either Trimesta or matching placebo in addition to glatimer acetate (Copaxone®), an FDA-approved therapy for MS, to women between the ages of 18-50 who have been recently diagnosed with relapsing-remitting MS. Each MS patient will be dosed and monitored for two years after being enrolled in the clinical trial. With over $8 million in grant funding awarded to date, the ongoing Trimesta clinical trial should be funded to its completion.

    Source: Adeona Pharmaceuticals, Inc. (19/09/11)

    Trimesta™ (oral estriol) MS trial receives research grant

    Adeona LogoAdeona Pharmaceuticals, Inc. announced today that after scientific review, the ongoing clinical trial of its Trimesta™ (oral estriol) drug candidate for multiple sclerosis (MS) has received an additional $1,594,553 in grant funding from the National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS).

    The clinical trial is led by Rhonda Voskuhl, M.D., Director, University of California, Los Angeles (UCLA) Multiple Sclerosis Program, UCLA Department of Neurology. Along with the recent grant award of $409,426 received from the National Multiple Sclerosis Society (NMSS), this NIH/NINDS grant award should support the ongoing Trimesta clinical trial to its completion.

    "The goal of this clinical trial is to demonstrate a reduction in the rate of relapses in female MS patients with a treatment regimen of oral Trimesta added to the standard of care Copaxone®. MS is a debilitating disease, therefore, slowing the progression of the disease could potentially allow these patients to achieve a more normal quality of life," said Dr. Voskuhl. "We are very grateful to the NIH for supporting this important mission. Their commitment to pursuing estriol as a novel treatment for MS has been unwavering."

    This ongoing clinical trial previously received a $5 million grant from the NMSS in partnership with the NMSS's Southern California chapter, with support from the National Institutes of Health, $860,440 in grant funding through the American Recovery and Reinvestment Act, and recent additional funding of $409,426 from the NMSS. In November 2010, Adeona announced that it was awarded $244,480 under the Qualifying Therapeutic Discovery Project Program to support research and development expenses related to the Company's MS program.

    The 150-patient, randomized, double-blind, placebo-controlled clinical trial of Trimesta is currently underway at 15 centers in the United States. Investigators are administering either Trimesta or matching placebo in addition to glatimer acetate (Copaxone®), an FDA-approved therapy for MS, to women between the ages of 18-50 who have been recently diagnosed with relapsing-remitting MS. With 133 out of 150 patients enrolled in the clinical trial as of May 1, 2011, the Company anticipates full enrollment by the second half of 2011.

    "We are very pleased that the Trimesta MS clinical trial has been awarded over $8 million in grant funding by organizations such as the NIH, NMSS and other third party groups. This support demonstrates independent scientific review of the clinical work being conducted by Dr. Voskuhl and provides funding for our MS program that is non-dilutive to our shareholders," stated James S. Kuo, M.D., M.B.A., Adeona's Chairman and CEO. "We are also excited to be exploring new opportunities with Dr. Voskuhl that could further expand our MS clinical program beyond the current trial."

    Source: Adeona Pharmaceuticals, Inc. (03/05/11)

    Trimesta™ Multiple Sclerosis trial receives $409,426 grant

    Adeona LogoAdeona Pharmaceuticals, Inc. announced today that the ongoing clinical trial of its Trimesta™ (oral estriol) drug candidate has received an additional $409,426 in grant funding from the National Multiple Sclerosis Society (NMSS). The clinical trial is led by, Rhonda Voskuhl, M.D., Director, University of California Los Angeles (UCLA) Multiple Sclerosis Program, UCLA Department of Neurology.

    Adeona also announced that as of March 1, 2011, the clinical trial evaluating the reduction in the rate of relapses in female multiple sclerosis (MS) patients is 85% enrolled.

    "We are very grateful to the NMSS for its continuous support of this MS program, from the preclinical development to the pilot and multi-center clinical trials, and now this current grant funding," said Dr. Voskuhl. "Their commitment to pursuing estriol for MS could potentially lead to a new, safe and effective oral therapy for this debilitating disease."

    This ongoing clinical trial previously received a $5 million grant from the NMSS in partnership with the NMSS's Southern California chapter, with support from the National Institutes of Health, and $860,440 in grant funding through the American Recovery and Reinvestment Act. In November 2010, Adeona announced that it was awarded $244,480 under the Qualifying Therapeutic Discovery Project Program to support research and development expenses related to the Company's MS program.

    The 150-patient, randomized, double-blind, placebo-controlled clinical trial of Trimesta is currently underway at 15 centers in the United States. Investigators are administering either Trimesta or matching placebo along with glatimer acetate (Copaxone®), an FDA-approved therapy for MS, to women between the ages of 18-50 who have been recently diagnosed with relapsing-remitting MS. With 127 out of 150 patients enrolled in the clinical trial by March 1, 2011, the Company anticipates full enrollment by the second half of 2011.

    About Adeona Pharmaceuticals, Inc.
    Adeona is a pharmaceutical company developing innovative medicines for the treatment of serious central nervous system diseases. The Company's strategy is to license product candidates that have demonstrated a certain level of clinical efficacy and develop them to a stage that results in a significant commercial collaboration. Currently, Adeona is developing the following product candidates: a prescription medical food for Alzheimer's disease, and drugs for multiple sclerosis, fibromyalgia, age-related macular degeneration and rheumatoid arthritis.

    SOURCE Adeona Pharmaceuticals, Inc (28/03/11)

    Adeona announces completion of 50% enrollment in Trimesta(TM) Multiple Sclerosis clinical trial

    Adeona LogoAdeona Pharmaceuticals, Inc. announced today that the clinical trial of its investigational drug Trimesta(TM) (estriol oral) being conducted by principal investigator Dr. Rhonda Voskuhl (Director, UCLA Multiple Sclerosis Program, UCLA Dept. of Neurology) has enrolled over 75 patients. The total planned enrollment is 150 patients.

    The Trimesta(TM) study is a double-blind, placebo-controlled clinical trial. Sixteen sites in the United States are currently enrolling patients. Investigators at these clinical sites are administering either Trimesta(TM) along with glatimer acetate (Copaxone(R)), an FDA approved therapy for multiple sclerosis, or a placebo plus glatimer acetate to women between the ages of 18 to 50 who have been recently diagnosed with relapsing-remitting multiple sclerosis.

    The primary endpoint is relapse rates at two years with a one year interim analysis using standard clinical measures of multiple sclerosis disability. Secondary endpoints of magnetic resonance imaging measurements of brain lesion and effects on cognition will also be studied.

    The Trimesta(TM) clinical trial has received a $5 million grant from the National Multiple Sclerosis Society in partnership with the National Multiple Sclerosis Society's Southern California chapter, with support from the National Institutes of Health. In January of 2010, it was announced that an additional $860,440 in grant funding had been received allowing the number of clinical sites enrolling patients for this study to more than double to 16 clinical sites.

    Trimesta(TM) has previously completed a 22-month, single-agent, crossover clinical trial in the United States for the treatment of relapsing remitting multiple sclerosis. The results showed the total volume and number of enhancing pathogenic myelin lesions (established neuroimaging measurements of disease activity in multiple sclerosis) decreased during the treatment period as compared to a six-month pretreatment baseline period. The median total enhancing lesion volumes decreased by 79 percent (p=0.02) and the number of lesions decreased by 82 percent (p=0.09) within the first three months of treatment with Trimesta(TM).

    "We are encouraged with the accelerated pace of patient enrollment in the Trimesta clinical trial," stated James S. Kuo, M.D., M.B.A., Adeona's Chairman and CEO. "Based on the previous clinical trial results, we are hopeful that we will see an improvement in cognition in multiple sclerosis patients. Such a clinical finding would serve a compelling clinical need in these patients and highly differentiate the product from others currently in development."

    Source: Adeona Pharmaceuticals, Inc. (23/02/10)

    Additional $860,000 grant for oral Estriol Multiple Sclerosis clinical trial announced

    Adeona LogoAdeona Pharmaceuticals, Inc., has announced that the ongoing clinical trial of its Trimesta™ (oral estriol) drug candidate being conducted by Dr. Rhonda Voskuhl, Director, UCLA Multiple Sclerosis Program, UCLA Dept. of Neurology has received an additional $860,440 in grant funding through the American Recovery and Reinvestment Act.

    The current phase II/III clinical study is a double-blind, placebo-controlled trial taking place at sixteen sites in the US and will enroll up to 150 female Multiple Sclerosis (MS) patients. Investigators will administer Trimesta along with glatiramer acetate (Copaxone®), an FDA approved therapy for MS, to women between the ages of 18-50 who have been recently diagnosed with relapsing-remitting MS. This ongoing clinical trial previously received a $5 million grant from the National Multiple Sclerosis Society (NMSS) in partnership with the National MS Society's Southern California chapter, with support from the National Institutes of Health (NIH).

    According to Dr. Voskuhl, "This additional funding has already had a very positive impact on our trial. It has greatly increased the rate of enrollment by supporting the addition of 9 more clinical sites, bringing the total up to 16 sites across the US. We were extremely pleased that our trial was deemed important enough to be supplemented with these additional funds."

    Previous Phase II Clinical Trial Results in Relapsing Remitting Multiple Sclerosis

    Trimesta (oral estriol) has previously completed an initial 22-month, single-agent, crossover Phase I/II clinical trial in the US for the treatment of MS in relapsing remitting patients, with highly encouraging results. The results showed the total volume and number of enhancing pathogenic myelin lesions (established neuroimaging measurements of disease activity in MS) decreased during the treatment period as compared to a six-month pretreatment baseline period. The median total enhancing lesion volumes decreased by 79 percent (p=0.02) and the number of lesions decreased by 82 percent (p=0.09) within the first three months of treatment with Trimesta. Following a six-month drug holiday during which the patients weren't on any drug therapies, Trimesta therapy was reinitiated during a four-month retreatment phase of this clinical trial. The relapsing-remitting MS patients again demonstrated a decrease in enhancing lesion volumes of 88 percent (p=0.008) and a decrease in the number of lesions by 48 percent (p=0.04) compared with original baseline scores (1),(2).

    Improvement in Cognitive Testing Scores

    During the prior Phase I/II clinical trial, a 14-percent improvement in Paced Auditory Serial Addition Test ("PASAT") cognitive testing scores (p=0.04) was also observed in the MS patients at six months of therapy. PASAT is a routine cognitive test performed in patients with a wide variety of neuropsychological disorders such as MS. The PASAT scores were expressed as a mean percent change from baseline and were significantly improved in the relapsing-remitting group.

    About the Trimesta Phase II/III Study

    In the current phase II/III study, Trimesta is being given orally once-a-day versus placebo to 150 female relapsing-remitting MS patients in combination with a standard of care background therapy, subcutaneously injected glatimer acetate. The primary endpoint for the study will evaluate effects of the treatment combination on relapse rates at two years with a one year interim analysis using standard clinical measures of MS disability as well as secondary endpoints of magnetic resonance imaging measurements of brain lesion and effects on cognition. The study is approaching 50% enrollment with the rate of enrollment benefiting significantly from the expansion of clinical sites.

    Source: Adeona Pharmaceuticals, Inc (11/01/10)

    Adeona pharmaceuticals expands patent estate for oral TRIMESTA

    Adeona Pharamceuticals Logo

    Adeona Pharmaceuticals, Inc. has announced that it has expanded its intellectual property estate through an option agreement to license with the University of Kansas relating to various uses of oral estriol for the treatment of various immunomodulatory diseases. TRIMESTA (oral, once-daily estriol) is being developed in an ongoing double-blind, phase IIb clinical trial for the treatment of relapsing remitting multiple sclerosis.

    Dr. B. T. Zhu, Professor of Pharmacology, Toxicology and Therapeutics at the University of Kansas, has demonstrated that estriol has strong immunomodulating effects versus other estrogens through its ability to reduce the risk of developing antibody-mediated immune attacks. These results are detailed in a peer reviewed scientific journal article entitled, "Unique effect of the pregnancy hormone estriol on antigen-induced production of specific antibodies in female BALB/c mice," contained within the March 2008 issue of the scientific journal Steroids, 73(3):289-98.

    Dr. Zhu commented, "We are pleased to have entered into this agreement with Adeona. Our research, along with that of Dr. Voskuhl, has clearly differentiated estriol from other estrogens, such as estradiol. We look forward to seeing additional results on the effectiveness of estriol from the ongoing immunomodulating preclinical studies."

    James Baxendale, Executive Director of the University of Kansas Center for Technology Commercialization commented, "Collaborating with industrial partners such as Adeona is key to the transfer of our intellectual property into the private sector. We have been impressed with Adeona's collaborative efforts for TRIMESTA and its advanced stages of development."

    Nicholas Stergis, Adeona's Chief Executive Officer commented, "This expansion of our intellectual property through collaborative university based relationships complements our existing issued patent estate for TRIMESTA, which has been exclusively licensed from UCLA. Dr. Zhu's work may help to expand the utility of TRIMESTA into other autoimmune diseases."

    TRIMESTA is the subject of an ongoing multi-center, double-blind, placebo-controlled 150-patient phase IIb clinical trial for the treatment of relapsing remitting multiple sclerosis (MS) which is being funded by a $5 million grant from the National Multiple Sclerosis Society (NMSS) in partnership with the National MS Society's Southern California chapter, with support from the National Institutes of Health (NIH).

    About TRIMESTA

    TRIMESTA is an orally active, immunomodulatory and anti-inflammatory molecule which has been approved and marketed throughout Europe and Asia for approximately 40 years for the treatment of post-menopausal hot flashes, but which has never been introduced in North America. Estriol, the active ingredient in TRIMESTA, is a weak estrogenic-based molecule that is produced in the placenta by women during pregnancy.

    Estriol is considered to play an important role in the immunologic privilege offered to the fetus during pregnancy, and is also thought to be responsible for the spontaneous remission of Th1-mediated autoimmune diseases of women (such as multiple sclerosis, psoriasis and rheumatoid arthritis) during pregnancy, especially during the third trimester.

    Adeona has an exclusive worldwide license with UCLA (through the Regents of the University of California, Los Angeles) to the intellectual property rights surrounding TRIMESTA for which Dr. Voskuhl is an inventor.

    Source: Adeona Pharmaceuticals, Inc (16/12/08)

    Estriol to be studied as Multiple Sclerosis treatment in UCLA trial

    Estriol and MS

    To try to develop kinder and more effective treatments for MS, Dr. Rhonda Voskuhl, director of the UCLA multiple sclerosis program, is reexamining the natural history of the disease.

    Women get MS three to four times more often than men, and they tend to get it at a younger age, in their late 20s rather than their early 40s. It has also long been known that pregnant women with MS exhibit an 80% drop in their symptoms during their third trimester -- a larger drop than the 60% reduction seen with natalizumab (Tysabri).

    In the late 1990s, Voskuhl discovered that the female sex hormone, estriol, could suppress MS-like symptoms in a mouse model of the disease. Estriol is used in Europe for hormone replacement therapy in post-menopausal women and is considered one of the safest estrogen hormones. In 2003, Voskuhl ran a pilot study giving estriol to 10 nonpregnant women with MS and found that the women showed an 80% decline in inflammatory lesions in their brain.

    Because drug companies are rarely interested in funding trials for compounds not protected by patents, Voskuhl has spent five years piecing together funding from the National Institutes of Health and the Southern California Chapter of the National Multiple Sclerosis Society to run a two-year trial at several sites with about 130 patients. She is still enlisting patients for this trial, in which patients taking the approved therapeutic Copaxone (glatiramer acetate) are compared with those taking Copaxone and estriol.

    Source: Los Angeles Times Copyright 2008 Los Angeles Times (15/12/08)

    Pipex Pharmaceuticals' oral TRIMESTA Phase IIa clinical and preclinical findings presented at WCTRIMS

    Pipex Logo

    Pipex Pharmaceuticals, Inc. announced today that its scientific collaborator has presented new findings from a phase IIa clinical trial results using estriol for the treatment of multiple sclerosis at the World Congress on Treatment and Research in Multiple Sclerosis Meeting (ACTRIMS, ECTRIMS and LACTRIMS) in Montreal, Canada. Estriol is the active ingredient in TRIMESTA.

    In a presentation from the laboratory of Dr. Rhonda Voskuhl, Professor of Neurology at UCLA, new findings were shown which demonstrated that estriol treatment decreases matrix metalloproteinase (MMP). MMP plays a crucial role in the migration of inflammatory cells into the CNS. Elevated levels of MMP-9 have been described in serum and CSF of multiple sclerosis patients, and they predict the occurrence of new active lesions on brain MRIs. This was demonstrated in both MS subjects treated with estriol in a pilot phase IIa clinical trial as well as in animals with experimental autoimmune encephalomyelitis (EAE), the MS animal model. The decrease in MMP-9 correlated with a decrease in enhancing lesions by MRI in MS, and with a decrease in inflammatory lesions by pathology in EAE, respectively.

    Selective estrogen receptor agonists were then used in the MS model to show that the mechanism through which estriol decreased MMP was through estrogen receptor (ER) alpha. In conclusion, estriol acting via ER alpha to reduce MMP-9 from immune cells is one mechanism potentially underlying the estriol-mediated reduction in enhancing lesions in MS and inflammatory lesions in EAE.

    Dr. Voskuhl's group have previously reported TRIMESTA's effect on immune modulation, MRI and cognitive testing from this clinical study (1)(2).

    TRIMESTA is the subject of an ongoing multi-center, double-blind, placebo-controlled 150-patient phase IIb clinical trial for the treatment of relapsing remitting multiple sclerosis (MS) which is being funded by a $5 million grant from the National Multiple Sclerosis Society (NMSS) in partnership with the National MS Society's Southern California chapter, with support from the National Institutes of Health (NIH).

    About TRIMESTA
    TRIMESTA is an orally active, immunomodulatory and anti-inflammatory molecule which has been approved and marketed throughout Europe and Asia for approximately 40 years for the treatment of post-menopausal hot flashes, but which has never been introduced in North America. Estriol, the active ingredient in TRIMESTA, is a weak estrogenic-based molecule that is produced in the placenta by women during pregnancy. Estriol is considered to play an important role in the immunologic privilege offered to the fetus during pregnancy, and is also thought to be responsible for the spontaneous remission of Th1-mediated autoimmune diseases of women (such as multiple sclerosis, psoriasis and rheumatoid arthritis) during pregnancy, especially during the third trimester. Pipex has an exclusive worldwide license with UCLA (through the Regents of the University of California) to the intellectual property rights surrounding TRIMESTA for which Dr. Voskuhl is an inventor.

    Pregnancy and MS

    Doctors have known for decades that women often experience a sharp drop in MS disease symptoms during the course of pregnancy, specifically in the third trimester when the levels of estriol is being produced at their highest level by the placenta. The list of autoimmune diseases that improve during pregnancy includes multiple sclerosis, rheumatoid arthritis, thyroiditis, uveitis, juvenile rheumatoid arthirits, ankylosing spondylitis with peripheral arthritis and psoriatic arthritis.

    A landmark clinical study published in the New England Journal of Medicine, known as the PRIMS study (Pregnancy in Multiple Sclerosis) followed 254 women with MS during 269 pregnancies and for up to one year after delivery. The PRIMS study demonstrated that relapse rates were significantly reduced by 71 percent (p < 0.001) through the third trimester of pregnancy from pre-baseline levels and relapse rates then increased by 120 percent (p < 0.001) during the first three months postpartum before returning to pre-pregnancy rates (3).

    (1) Sicotte NL, Liva SM, Klutch R, Pfeiffer P, Bouvier S, Odesa S, Wu TC, Voskuhl RR. Treatment of multiple sclerosis with pregnancy hormone estriol. Ann Neurol. 2002 Oct. 52(4):421-8.
    (2) Soldan SS, Alvarez Retuerto AI, Sicotte NL, Voskuhl RR. Immune modulation in multiple sclerosis patients treated with pregnancy hormone estriol. J Immunol. 2003 Dec 1:171(11):6267-74.
    (3) Confavreux, C., Hutchinson, M., Hours, M.M., Cortinovis-Tourniaire, P., and Moreau, T. Rate of pregnancy-related relapse in multiple sclerosis. 1998. Pregnancy in Multiple Sclerosis Group. N Engl J Med 339:285-291.

    Source: Marketwatch © 2008 MarketWatch, Inc. (19/09/08)

    Study uses hormones to treat multiple sclerosis
    Pregnant multiple sclerosis patients have long noticed a sharp reduction in their symptoms - only to see them reappear after giving birth.

    It's what tipped off researchers to the potential power of estriol, a type of estrogen that surges during the second and third trimesters of pregnancy to help prevent the body from rejecting the fetus. But new research shows it may do much more.

    In a pilot study at UCLA, women took Trimesta, a synthesized form of estriol used in Europe and Asia for treating hot flashes. They showed an 80 percent reduction in M.S.-related lesions on the brain within three months of treatment. After six months, their cognitive function improved by 14 percent.

    Now the Pipex Pharmaceuticals drug is being studied at the University of Utah and six other sites in the US in a three-year, Phase II clinical study.

    About 150 women with relapsing-remitting M.S. will participate, half of whom will be injected with Copaxone - a common drug therapy for M.S. - and take placebo pills, while the other half will receive the injections plus estriol pills.

    "We're very excited about this trial because we think it will be a completely new direction for women with M.S.," said John Rose, chief of neurology at the VA Medical Center and a professor of neurology at the U. "The mechanism of action of the drug looks to be very gentle, but potentially very effective."

    During pregnancy, Rose said, women experience a shift in their immune system, from cells protecting them from disease to antibodies taking on the role. The change works to the advantage of M.S. patients, whose cells secrete proteins that trigger an autoimmune response.

    Estriol, it is believed, may play a role in this change in immune repose.

    The goal of the study, said Rhonda Voskuhl, a professor of neurology at UCLA, is to see if estriol leads to a reduction in relapses, disabilities such as fatigue and depression, and brain atrophy. She's also eager to see if it leads to better "neuroprotection," reducing the ability of immune cells to attack the brain while at the same time making it more resistant to damage.

    Voskuhl, the overall principal investigator, showed in her pilot study that estriol stimulated cells to rebuild the brain's protective coating of myelin, a fatty nerve-insulating protein that's typically worn thin or disintegrated by M.S. The resulting neuron inflammation leads to the formation of lesions or plaques on the brain.

    Voskuhl said interest and research in estriol was in part stimulated by the National Multiple Sclerosis Society's creation of a task force to explore gender and M.S.

    "The National MS Society recognized in 1997, as a field, that it is very fertile to discover new suppressive mechanisms," she said.

    On the horizon, Voskuhl said, are larger studies to explore how testosterone may reduce M.S. symptoms in men. The hormone is already used to prevent muscle wasting in male HIV patients and cognitive degeneration in the elderly.

    One pilot study conducted by Voskuhl showed that testosterone - which converts to estrogen in the brain - may also have a measurable impact on M.S. symptoms in men, though not to the extent estriol does in women, she said.

    "We showed improvement in cognition and also slowing of brain atrophy," she said.

    Added Rose, "All of these hormones have many different analogs. It could be that something a little bit special will have an impact, but I don't know we'll have . . . an equivalent right away."

    Source: The Salt Lake Tribune © medianewsgroup.com (11/04/08)

    Pipex Pharmaceuticals Announces First Notice of Allowance for U.S. Patent Covering Uses of Low Potency Bioidentical Estrogens for the Treatment of Autoimmune Diseases of Women

    Claims Covering Use of Estrogens, Including TRIMESTA, in Combination With Popular Immunotherapies to Treat Multiple Sclerosis.

    Pipex Pharmaceuticals, Inc. a specialty pharmaceutical company developing innovative late-stage drug candidates for the treatment of neurologic and fibrotic diseases, announced today that it has received a notice of allowance from the US Patent Office for claims to a patent which covers the use of estrogens in combination with other FDA-approved multiple sclerosis therapies for the treatment of autoimmune diseases.

    Pipex's product candidate TRIMESTA (oral, once-daily estriol), which is covered by this notice of allowance, is currently in a Phase III multi-center, placebo-controlled clinical trial in combination with Copaxone for treatment of multiple sclerosis that is being funded by a $5 million grant from the National Multiple Sclerosis Society, its largest single grant ever for a clinical trial.

    Once issued, this US Patent No. 10/275,833 entitled "Method of treating immune pathologies with low-dose estrogen" will cover the use of estrogens and their derivatives at serum concentrations above basal and below pregnancy levels in combination with various immunotherapeutic agents, such as Avonex®, Betaseron®, Copaxone®, Rebif® , and Enbrel®, for the treatment of Th1-mediated autoimmune diseases including multiple sclerosis (MS), psoriasis, and rheumatoid arthritis (RA). The corresponding US and Japanese patents are currently pending.

    Estriol, the active ingredient of TRIMESTA, a low potency bioidentical estrogen used by millions of women in Europe and Asia for over 30 years has been shown in large case controlled studies conducted in Europe to have a substantially reduced risk of breast cancer compared to the limited FDA-approved estrogens available to American women. On January 9th of this year, in response to a citizen's petition filed by Wyeth, a large pharmaceutical company that markets potent horse derived estrogens, the FDA took action to limit the availability of low potency estrogens as a treatment option available to American women.

    "This notice of allowance supplements our intellectual property estate which already includes US Patent No. 6,936,599 covering the use of TRIMESTA (oral, once daily estriol) at pregnancy levels for the treatment of multiple sclerosis as well as our European patent which issued last year. It will be an important addition to our leadership position in the use of bioidentical estrogens for women's health. We hope that the notice of allowance from this important patent estate will be followed by further allowances covering uses of estriol at physiologic levels to treat autoimmune diseases of women," said Steve H. Kanzer, Pipex's chairman and CEO.

    Through a wholly owned subsidiary, Pipex has obtained exclusive licenses to these patents from the University of California, Los Angeles (UCLA) and Oregon Health & Sciences University (OHSU).

    About Oral TRIMESTA

    TRIMESTA (oral estriol) is an orally active immunomodulatory and anti-inflammatory molecule that has been approved and marketed throughout Europe and Asia for the past 30 years for the treatment of post-menopausal hot flashes, but which has never been introduced in North America. Estriol, the active ingredient in TRIMESTA, is a weak estrogenic-based molecule that is produced by women in the placenta during pregnancy. Estriol is considered to play an important role in the immunologic privilege offered to the fetus during pregnancy, and it is also thought to be responsible for the spontaneous remission of Th1-mediated autoimmune diseases, such as multiple sclerosis and psoriasis, in women during pregnancy, especially during the third trimester. TRIMESTA has completed a 22-month crossover Phase II clinical trial for the treatment of MS and recently entered a Phase II/III clinical trial under a $5 million grant from the National MS Society.

    About the Phase II/III Clinical Trial

    The clinical study is a double-blind placebo-controlled trial that is currently taking place at six sites in the US, enrolling up to 150 female MS subjects. Investigators are administering TRIMESTA to women between the ages of 18-50 who have been recently diagnosed with relapsing-remitting MS. TRIMESTA is given in combination with subcutaneously injected Copaxone®, a standard of care treatment for MS. The team is evaluating effects of the treatment combination on relapse rates by using several clinical and magnetic resonance imaging measures of disability progression.

    Source: Pipex Pharmaceuticals, Inc. (01/02/08)

    The Food and Drug Administration has launched a misguided attack on estriol despite overwhelming evidence it is safe and effective for women in menopause and multiple sclerosis

    "Why would the FDA try to take estriol off the market when it is not only safe for women in menopause, it may even help women with multiple sclerosis," writes Dr. Erika Schwartz MD. "Maybe it is because the agency is more concerned with protecting Wyeth than it is with protecting women", she says.

    Wyeth is the manufacturer of the top-selling synthetic hormone replacement therapies on the market. Earlier this month, the FDA sent warning letters to compounding pharmacies threatening a ban on estriol. The FDA said its action was in response to a "citizen's petition" voicing concern about compounded bioidentical hormones submitted by Wyeth to the FDA October 2005.

    In her blog, Dr. Erika explains what estriol is, how it works and how it has been studied in this country and overseas since the 1980s.

    She notes that Jonathan Wright MD, an American leader in the field of bioidentical hormone therapies, created a combination of estriol and estradiol known as Biest to treat symptoms of menopause. The success of this combination has translated in its extensive use by compounding pharmacies around the country for the past 10 years.

    Most recently estriol has been studied in the treatment of multiple sclerosis in women. It is a scientifically supported and well known fact that women who suffer with autoimmune diseases like rheumatoid arthritis, thyroiditis and MS experience significant improvement in these conditions during pregnancy. Since estriol is the dominant estrogen during pregnancy, research is presently being conducted to evaluate estriol's effect on MS.

    Doses of estriol similar to those circulating in the blood stream of a pregnant woman in the middle of her pregnancy (6-8 mg/day) have shown significant remission of the disease and hold much promise. Dr. Rhonda Voskuhl at UCLA has been conducting very important estriol studies on women with MS and the results are very promising.

    In an article on NeurologyReviews.com in 2002 Dr. Voskuhl was quoted as saying estriol at pregnancy doses had been given in Europe and Asia in the form of hormone replacement therapy for symptoms of menopause, "which means we didn't have to reinvent the wheel on assessing toxicity. It was very well known how this estriol preparation would be tolerated. Therefore we could go straight to a phase I clinical trials focusing on multiple sclerosis-related disease measures."

    Dr. Erika says: "No adverse reactions or long term negative side-effects have been reported with the use of estriol by physicians or patients using this bioidentical hormone to the FDA to my knowledge."

    Source: PRWeb (23/01/08)

    Pipex Pharmaceuticals Announces Broadly Issued European Patent Covering Uses of Oral TRIMESTA for the Treatment of Autoimmune Diseases, Including Multiple Sclerosis

    Claims Covering Use of Estrogens Including TRIMESTA, in Combination With Popular Immunotherapies to Treat Multiple Sclerosis.

    Pipex Pharmaceuticals, Inc, a specialty pharmaceutical company developing innovative late-stage drug candidates for the treatment of neurologic and fibrotic diseases, announced today that it has received a broadly issued European patent which covers the use of estrogens in combination with other FDA-approved multiple sclerosis therapies for the treatment of autoimmune diseases.

    The issued European patent, EP1286664 entitled, "Combination of Low Dose Estrogen and Immunotherapeutic Agent for Treating Immune Diseases," covers the use of estrogens and their derivatives at serum concentrations above basal and below pregnancy levels in combination with various immunotherapeutic agents, such as, Avonex®, Betaseron®, Copaxone®, Rebif® and Enbrel® for the treatment of Th1-mediated autoimmune diseases, such as, multiple sclerosis (MS), psoriasis and rheumatoid arthritis (RA). The corresponding U.S. and Japanese patents are currently pending.

    "This patent issuance supplements our intellectual property estate which already includes U.S. Patent No. 6,936,599 which covers the use of TRIMESTA at pregnancy levels for the treatment of multiple sclerosis. This issued patent is an important addition to our leadership position in estrogen therapy for the treatment of autoimmune disease in women," said Steve H. Kanzer, Pipex's Chairman and CEO.

    Through a wholly owned subsidiary, Pipex has obtained exclusive licenses to these patents from the University of California, Los Angeles (UCLA) and Oregon Health & Sciences University (OHSU).

    About Oral TRIMESTA

    TRIMESTA (oral estriol) is an orally active immunomodulatory and anti-inflammatory molecule that has been approved and marketed throughout Europe and Asia for the treatment of post-menopausal hot flashes for approximately 30 years, but has never been introduced in North America. Estriol, the active ingredient in TRIMESTA, is a weak estrogenic-based molecule that is produced in the placenta by women during pregnancy. Estriol is considered to play an important role in the immunologic privilege offered to the fetus during pregnancy and is also thought to be responsible for the spontaneous remission of Th1-mediated autoimmune diseases of women (such as multiple sclerosis and psoriasis) during pregnancy, especially during the third trimester. TRIMESTA has completed a 22-month crossover Phase II clinical trial for the treatment of MS and has recently entered a Phase II/III clinical trial under a $5 million grant from the National MS Society.

    About the Phase II/III Clinical Trial

    The clinical study is a double-blind, placebo-controlled trial that is currently taking place at seven sites in the U.S., enrolling up to 150 female MS subjects. Investigators are administering TRIMESTA to women between the ages of 18-50 who have been recently diagnosed with relapsing-remitting MS. TRIMESTA is given in combination with subcutaneously injected Copaxone®, a standard of care treatment for MS. The team is evaluating effects of the treatment combination on relapse rates using several clinical and magnetic resonance imaging measures of disability progression.

    The study sites include the University of California, Los Angeles (UCLA), Ohio State University (OSU), Rutgers University (UMDNJ), Washington University, St. Louis, University of Chicago, University of Utah and Wayne State University.

    Source: Pipex Pharmaceuticals, Inc (06/09/07)

    Pipex Pharmaceuticals' Oral TRIMESTA Initiates Dosing in Phase II/III Clinical Trial for Multiple Sclerosis
    Pipex Pharmaceuticals, Inc., a specialty pharmaceutical company developing innovative late-stage drug candidates for the treatment of neurologic and fibrotic diseases, announced today that it has initiated patient dosing of TRIMESTA (oral estriol), its proprietary therapy for multiple sclerosis (MS), in a multi-center Phase II/III clinical trial for the treatment of women with relapsing-remitting MS. This clinical trial has received a $5 million grant from the National Multiple Sclerosis Society (NMSS) in partnership with the National MS Society's Southern California chapter, with support from the National Institutes of Health (NIH).

    Dr. Rhonda Voskuhl, professor of neurology at the University of California, Los Angeles and inventor of TRIMESTA, commented, "We are delighted to be enrolling so shortly after recently initiating the Phase II/III clinical trial."

    Dr. Charles Bisgaier, Pipex's President, stated, "To our knowledge, this is the first gender-specific, oral, potentially disease-modifying agent that has entered later-stage clinical trials for the treatment of MS."

    Dr. Bisgaier went onto say, "Given the convenience of an oral drug therapy, such as TRIMESTA, we have received a lot of positive patient interest in this study and hope to continue enrolling at this positive rate."

    The Phase II/III clinical study is a double-blind, placebo-controlled trial that will take place at seven sites in the US and will enroll up to 150 female MS patients. Investigators will administer TRIMESTA along with COPAXONE, an FDA approved therapy for MS to women between the ages of 18-50 who have been recently diagnosed with relapsing-remitting MS.

    Previous Phase II Clinical Trial Results in Relapsing Remitting Multiple Sclerosis

    TRIMESTA (oral estriol) has completed an initial 22-month, single-agent, crossover Phase II clinical trial in the US for the treatment of MS in relapsing remitting patients, with highly encouraging results. The results showed the total volume and number of enhancing pathogenic myelin lesions (established neuroimaging measurements of disease activity in MS) decreased during the treatment period as compared to a six-month pretreatment baseline period. The median total enhancing lesion volumes decreased by 79 percent (p=0.02) and the number of lesions decreased by 82 percent (p=0.09) within the first three months of treatment with TRIMESTA.

    Following a six-month drug holiday during which the patients weren't on any drug therapies, TRIMESTA therapy was reinitiated during a four-month retreatment phase of this clinical trial. The relapsing-remitting MS patients again demonstrated a decrease in enhancing lesion volumes of 88 percent (p=0.008) and a decrease in the number of lesions by 48 percent (p=0.04) compared with original baseline scores (1),(2).

    Improvement in Cognitive Testing Scores

    During this Phase II clinical trial, a 14-percent improvement in Paced Auditory Serial Addition Test ("PASAT") cognitive testing scores (p=0.04) was also observed in the MS patients at six months of therapy. PASAT is a routine cognitive test performed in patients with a wide variety of neuropsychological disorders such as MS. The PASAT scores were expressed as a mean percent change from baseline and were significantly improved in the relapsing-remitting group.

    About The TRIMESTA Phase II/III Study

    TRIMESTA will be given in combination with subcutaneously injected Copaxone®, a standard treatment for MS. The team will evaluate effects of the treatment combination on relapse rates by using several clinical and magnetic resonance imaging measures of disability progression.

    The study sites include the University of California, Los Angeles (UCLA), Ohio State University (OSU), Rutgers University (UMDNJ), Washington University, St. Louis, University of Chicago, University of Utah, and Wayne State University.

    (1) Sicotte NL, Liva SM, Klutch R, Pfeiffer P, Bouvier S, Odesa S, Wu TC, Voskuhl RR. Treatment of multiple sclerosis with pregnancy hormone estriol. Ann Neurol. 2002 Oct. 52(4):421-8.

    (2) Soldan SS, Alvarez Retuerto AI, Sicotte NL, Voskuhl RR. Immune modulation in multiple sclerosis patients treated with pregnancy hormone estriol. J Immunol. 2003 Dec 1:171(11):6267-74.

    Copaxone® is a registered trademark of Teva Pharmaceuticals.

    Source: Pipex Pharmaceuticals, Inc. (16/07/07)

    Pipex Pharmaceuticals' Oral TRIMESTA Initiates Enrollment of Phase II/III Clinical Trial for Multiple Sclerosis
    $5 Million Grant From National Multiple Sclerosis Society, With Support From NIH.

    Previous Phase II Demonstrated 79% Reduction in Gadolinium Enhancing Brain (MS Lesion) Volumes (p=0.02) and Exceptional 14% Increase in Cognitive Function (p=0.04)

    Pipex Pharmaceuticals, Inc. a specialty pharmaceutical company developing innovative late-stage drug candidates for the treatment of neurologic and fibrotic diseases, announced today that TRIMESTA (oral estriol), its proprietary therapy for multiple sclerosis (MS) has entered a multi-center, Phase II/III clinical trial for the treatment of women with relapsing-remitting MS. This clinical trial has received a $5 million grant from the National Multiple Sclerosis Society (NMSS) in partnership with the National MS Society's Southern California chapter, with support from the National Institutes of Health (NIH).

    Previous Phase II Clinical Trial Results in Relapsing Remitting Multiple Sclerosis

    TRIMESTA (oral estriol) has completed an initial 22 month, single-agent, crossover phase II clinical trial in the U.S. for the treatment of MS in relapsing remitting patients, with highly encouraging results.

    The results showed the total volume and number of enhancing pathogenic myelin lesions (established neuroimaging measurements of disease activity in MS) decreased during the treatment period as compared to a six-month pretreatment baseline period. The median total enhancing lesion volumes decreased by 79 percent (p=0.02) and the number of lesions decreased by 82 percent (p=0.09) within the first three months of treatment with TRIMESTA.

    Following a three month drug holiday during which the patients weren't on any drug therapies, TRIMESTA therapy was reinitiated during a retreatment phase of this clinical trial. The relapsing-remitting MS patients again demonstrated a decrease in enhancing lesion volumes of 88 percent (p=0.008) and a decrease in the number of lesions by 48 percent (p=0.04) compared with original baseline scores (1), (2).

    Improvement in Cognitive Testing Scores

    During this phase II clinical trial, a 14 percent improvement in Paced Auditory Serial Addition Test ("PASAT") cognitive testing scores (p=0.04) was observed in these MS patients at six months of therapy. PASAT is a routine cognitive test performed in patients with a wide variety of neuropsychological disorders such as MS. The PASAT scores were expressed as a mean percent change from baseline and were significantly improved in the relapsing-remitting group.

    Dr. Rhonda Voskuhl, Professor of Neurology at the University of California, Los Angeles and inventor of TRIMESTA, commented, "Due to its rapid onset of action, oral activity and high response rate seen in relapsing-remitting MS patients in the initial Phase II clinical trial, TRIMESTA may have an important clinical advantage over current injectable MS treatments. As a neurologist, the improvement in cognitive testing scores may also represent a new paradigm in treating MS patients as well as other neurodegenerative diseases with TRIMESTA."

    Dr. John R. Richert, Executive Vice President of Research and Clinical Programs at the National MS Society, stated, "We're encouraged that the National MS Society's funding of the original pilot trial of estriol, which emerged from targeted research on gender differences in MS, has led to this new trial. We are pleased that Pipex and Dr. Voskuhl are committed to advancing the development of this novel approach which could potentially lead to an affordable, oral disease-modifying therapy for this debilitating disease."

    Dr. Charles Bisgaier, Pipex's President, stated that, "The active ingredient in TRIMESTA has been marketed for over 40 years in Europe and Asia for the treatment of post-menopausal hot flashes. As we enter this Phase II/III clinical trial of TRIMESTA for treatment of MS, the product's known historical efficacy and tolerability coupled with the promising Phase II clinical trial results in MS patients an exciting new approach to treating this devastating disease with a targeted orally active drug candidate."

    Dr. Bisgaier went onto say, "The exceptional increase in cognitive function together with the rapid reduction in lesion volumes and numbers positions TRIMESTA to become therapy of choice in the $10 billion global MS market. We are grateful for this $5 million grant and the support of the NMSS/NIH. We are excited about working with the National MS Society, Dr. Voskuhl and her team in furthering this promising new approach."

    About the Phase II/III Clinical Trial

    The clinical study is a double-blind, placebo-controlled trial that will take place at seven sites in the U.S., enrolling up to 150 female MS patients. Investigators will administer TRIMESTA to women between the ages of 18-50 who have been recently diagnosed with relapsing-remitting MS. TRIMESTA will be given in combination with subcutaneously injected Copaxone®, a standard treatment for MS. The team is evaluating effects of the treatment combination on relapse rates using several clinical and magnetic resonance imaging measures of disability progression.

    The study sites include the University of California, Los Angeles (UCLA), Ohio State University (OSU), Rutgers University (UMDNJ), Washington University, St. Louis, University of Chicago, University of Utah and Wayne State University. 

    Pregnancy and MS

    Doctors have known for decades that women often experience a sharp drop in MS disease symptoms during the course of pregnancy, specifically in the third trimester when the levels of estriol is being produced at their highest level by the placenta. The list of autoimmune diseases that improve during pregnancy includes multiple sclerosis, rheumatoid arthritis, thyroiditis, uveitis, juvenile rheumatoid arthirits, ankylosing spondylitis with peripheral arthritis and psoriatic arthritis.

    A landmark clinical study published in the New England Journal of Medicine, known as the PRIMS study (Pregnancy in Multiple Sclerosis) followed 254 women with MS during 269 pregnancies and for up to one year after delivery. The PRIMS study demonstrated that relapse rates were significantly reduced by 71 percent (p < 0.001) through the third trimester of pregnancy from prebaseline levels and relapse rates then increased by 120 percent (p < 0.001) during the first three months postpartum before returning to prepregnancy rates (3) .

    About TRIMESTA

    TRIMESTA is an orally active, immunomodulatory and anti-inflammatory molecule the has been approved and marketed throughout Europe and Asia for approximately 40 years for the treatment of post-menopausal hot flashes, but has never been introduced in North America. Estriol, the active ingredient in TRIMESTA, is a weak estrogenic-based molecule that is produced in the placenta by women during pregnancy. Estriol is considered to play an important role in the immunologic privilege offered to the fetus during pregnancy and is also thought to be responsible for the spontaneous remission of Th1-mediated autoimmune diseases of women (such as multiple sclerosis and rheumatoid arthritis) during pregnancy, especially during the third trimester. Pipex has an exclusive worldwide license with UCLA (through the Regent of the University of California) to the intellectual property rights surrounding TRIMESTA.

    About Pipex Pharmaceuticals, Inc.

    Pipex Pharmaceuticals Inc. is a specialty pharmaceutical company that is developing proprietary, late-stage drug candidates for the treatment of neurologic and fibrotic diseases. Pipex's strategy is to exclusively in-license proprietary, clinical-stage drug candidates and complete the further clinical testing, manufacturing and regulatory requirements sufficient to seek marketing authorisations via the filing of New Drug Applications (NDAs) with the FDA in the US and Marketing Application Authorizations (MAAs) with the European Medicines Evaluation Agency (EMEA).

    (1) Sicotte NL, Liva SM, Klutch R, Pfeiffer P, Bouvier S, Odesa S, Wu TC, Voskuhl RR. Treatment of multiple sclerosis with pregnancy hormone estriol. Ann Neurol. 2002 Oct. 52(4):421-8.

    (2) Soldan SS, Alvarez Retuerto AI, Sicotte NL, Voskuhl RR. Immune modulation in multiple sclerosis patients treated with pregnancy hormone estriol. J Immunol. 2003 Dec 1:171(11):6267-74.

    (3) Confavreux, C., Hutchinson, M., Hours, M.M., Cortinovis-Tourniaire, P., and Moreau, T. Rate of pregnancy-related relapse in multiple sclerosis. 1998. Pregnancy in Multiple Sclerosis Group. N Engl J Med 339:285-291.

    Copaxone® is a registered trademark of Teva Pharmaceuticals.

    Source: Pipex Pharmaceuticals, Inc. (11/06/07)

    Could Estriol Be the Elixir for Multiple Sclerosis
    It has long been common knowledge that pregnant women with multiple sclerosis (MS) experience a sharp drop in the disease's symptoms during the course of their pregnancy.

    Some years back, Dr. Rhonda Voskuhl, director of UCLA's Multiple Sclerosis Program, and her colleagues discovered the cause. They found that a female sex hormone called estriol, which is produced during pregnancy, was responsible for the suppression. Four years ago, Voskuhl followed that discovery with a pilot study in which 10 non-pregnant women with MS were given estriol, yielding what she described as "pretty remarkable" results --- an 80 percent drop in inflammatory lesions in the brain, a hallmark of the disease.

    This month, Voskuhl begins a much larger trial of estriol, one that will involve 150 patients at multiple locations over the next two years. The prospects, she said, are exciting.

    Multiple sclerosis is an autoimmune disease of the central nervous system that attacks the tissue surrounding the brain's nerve fibres. This tissue, called myelin, can be thought of as the insulation wrapped around an electrical wire. When the myelin is damaged, the nerve's ability to send signals to and from the brain is interfered with, resulting in symptoms common to MS, including problems with balance, memory, vision loss and more.

    Currently, anti-inflammatory drugs used to treat MS lessen the symptoms and slow the progression of the disease. But they must be given by injection daily, weekly or monthly --- depending on the drug --- and are expensive, costing between $12,000 to $24,000 a year.

    Estriol is a hormone produced by the placenta that is virtually undetectable until pregnancy, when it progressively increases. It is thought that its role is to suppress a woman's immune system when she is pregnant, so that the fetus will not be seen by the body as a foreign "invader."

    "The beauty of estriol is that it can be given as a pill, not a shot, and also that it's not a new drug; it has decades of safety behind it," said Voskuhl, who holds the Jack H. Skirball Chair for Multiple Sclerosis in the UCLA Department of Neurology. For years estriol has been in widespread use in Europe and Asia as hormone replacement therapy for women with menopausal symptoms. The fact that the pill already exists, she said, should dramatically reduce the cost of treatment.

    Most important of all, though, is that the drug potentially provides a one-two punch against MS, both reducing the ability of immune cells to attack the brain, as well as making the brain more resistant to damage if any immune cells do make it through.

    "It's a two-pronged approach--an anti-inflammatory prong to reduce the attacks, but also a neuroprotective prong to make the brain suffer less damage in case of an attack," said Voskuhl.

    In all, seven institutions from around the nation will be involved in the two-year study. The investigators plan to recruit 150 women who have not previously been treated for MS. They will be given either estriol along with Copaxone, an MS drug currently in use, or a placebo along with Copaxone. "That way, no one will receive less than the standard of care," Voskuhl said. The team will measure relapse rates over the course of the trial.

    Initial funding of $667,000 for the trial is being provided by the Southern California Chapter of the National Multiple Sclerosis Society. The total cost of the trial is expected to be $4.7 million.

    Source: Maxhealth © Copyright 2004-2005 eMaxHealth.com - HealthCare Articles. All Rights Reserved . (10/03/07)

    © Multiple Sclerosis Resource Centre

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    Avonex®
    AZ01
    Betaseron® (Betaferon®)
    BG-12
    Cannabis And Cannabinoid Research
    Copaxone®
    Cyclophosphamide
    Cyrevia
    Dextromethorphan
    Gilenya® (fingolimod)
    Laquinimod
    Lemtrada (alemtuzumab)
    Lisinopril
    Low Dose Naltrexone - Latest News
    Masitinib
    MIS416
    MN-166 (Ibudilast)
    NeuroVax
    Novantrone (Mitoxantrone)
    NT-KO-003
    Ocrelizumab
    ONO-4641
    PEGylated interferon beta
    PI-2301
    Rebif®
    RPC1063
    RPI-78M
    RTL-1000
    Sativex®
    SHK
    Statins
    Tcelna(TM)
    Tysabri®
    Zenapax (daclizumab)


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