Teva Pharmaceutical Industries Ltd. and Active Biotech presented data further illuminating the novel, dual mechanism of action (MOA) of investigational oral, once-daily, laquinimod for the treatment of relapsing-remitting multiple sclerosis (RRMS), conferring neuroprotective and anti-inflammatory properties. Results from several preclinical studies suggest that laquinimod elicits a protective therapeutic effect by reducing demyelination and inducing axonal protection.

These studies expand upon a growing body of data suggesting the mechanism of oral laquinimod in RRMS patients is targeted immunomodulation, and may help contribute to the favourable benefit-to-risk profile associated with this compound.

“MS patients, and the physicians who treat them, await the availability of an oral agent with an efficacy and safety profile required to address the chronic, lifelong nature of the disease,” explains Prof. Wolfgang Brück, head of the Neuropathology Dept., the Georg-August-Universität, Göttingen, Germany. “The seemingly targeted immunomodulation that appears to be associated with the dual MOA of laquinimod and the favourable benefit-to-risk profile seen in patients studied for up to 3.5 years, make the drug a potential candidate to address this unmet need for an oral therapy.”

Laquinimod received Fast Track designation from the U.S. Food and Drug Administration (FDA) in February 2009. Two global Phase III clinical trials, BRAVO and ALLEGRO, have completed enrollment and are currently ongoing.

ABOUT THE STUDIES

The studies evaluating the properties of laquinimod presented at ECTRIMS include:

* Laquinimod induces up-regulation of neurotrophins in serum of patients with relapsing-remitting multiple sclerosis (P 783, 15:30 – 17:00 Immunomodulation – 2, September 11, 2009)
R. Linker, J. Thöne, G. Comi, R. Gold (Bochum, DE; Rome, IT)

596 serum samples from RRMS patients participating in the LAQ/5062 trial were tested for the presence of neurotrophic factors, including neurotrophin (NT)-3, NT-4 and brain derived neurotrophic factor (BDNF). Data on the expression of neurotrophic factors were correlated with their functional activity in a neuronal survival assay. Treatment with 0.6 mg of laquinimod resulted in a significant and specific, up to 11-fold increase in BDNF serum levels as compared to baseline, as well as to placebo treatment after 3 months. Besides an immunomodulatory mechanism of action, laquinimod has the ability to increase levels of neurotrophic factors in vivo possibly contributing to neuroprotection in MS patients.

* Anti-inflammatory pathways activated by laquinimod in CD4+, CD8+, CD14+, CD19+ and NK peripheral blood cells subtypes of relapsing-remitting multiple sclerosis patients (P 264, 15:30-17:00 Immunomodulation – 2, September 10, 2009)
M. Gurevich, B. Timan, L. Hayardeny, A. Achiron (Ramat Gan, Netanya, IL)

High throughout gene expression analysis of in-vitro incubation of peripheral blood mononuclear cells from RRMS patients with laquinimod demonstrated that laquinimod induced in-vitro immunomodulatory effects that are characterized by activation of anti-inflammatory IL-4 pathway in CD4+ cells, promotion of apoptosis in CD8+ and B cells and suppression of metabolic activity of CD14+ and NK cells.

* Reduced inflammation, demyelination and axonal damage after therapeutic laquinimod treatment in experimental autoimmune encephalomyelitis (P 441, 15:30 – 17:30 Immunomodulation – 1, September 11, 2009)
C. Wegner, C. Stadelmann, W. Brück (Gottingen, DE)

In animal models of MS, laquinimod inhibits the development of acute and chronic experimental autoimmune encephalomyelitis (EAE). Laquinimod modulates the cytokine balance in favour of anti-inflammatory Th2/Th3 cytokines. Therapeutic treatment with laquinimod is effective in ameliorating the extent of macrophage and T cell infiltration, demyelination and axonal damage. Findings indicate that laquinimod might have an axon-protective effect in addition to its anti-inflammatory properties.

* The effect of laquinimod on the distribution of monocyte subsets (P 808, 15:30 – 17:00 Immunomodulation – 2, September 11, 2009)
T. Birnberg, S. Jung (Rehovot, IL)

Monocytes are circulating blood leukocytes that play important roles in inflammatory responses. In mice, monocytes originate in the bone-marrow from Macrophages and Dendritic cells precursor. Murine blood monocytes encompass two main Ly6Chi and Ly6Clow subsets. Recent evidence suggests that the ratio of the two monocyte subsets can have effects on the susceptibility of the organism to various disorders, including experimental autoimmune encephalomyelitis (EAE) lesions. These cells are accumulating in the blood and CNS immediately prior to EAE clinical episodes. The results indicate that the effect by which laquinimod exerts its clinical efficacy in autoimmune diseases may be due to its impact on the myeloid precursor cells.

Source: Zikkir © 2009 ZIKKIR WORLD (16/09/09)

Teva Pharmaceutical Industries and Active Biotech have completed patient enrollment for the second pivotal Phase III clinical trial, Bravo, evaluating the novel, oral once-daily immunomodulating compound, laquinimod, for the treatment of relapsing-remitting multiple sclerosis.

Bravo is a global clinical trial designed to evaluate the efficacy, safety and tolerability of laquinimod compared to placebo, and to provide risk-benefit data for laquinimod compared to a currently available injectable treatment, Avonex.

The Bravo study completed patient enrollment in June 2009, recruiting more than 1,200 patients at 156 sites in the US, Europe, Israel and South Africa.

Allegro, the first global Phase III trial of laquinimod, completed enrollment in November 2008, after recruiting more than 1,000 patients at 152 sites in North America, Europe and Asia, said Teva. The trial is currently ongoing.

Moshe Manor, Teva's group vice president of global branded products, said: "Teva and Active Biotech are encouraged by the potential of laquinimod to address patients' unmet need for an oral immunomodulating multiple sclerosis therapy that provides efficacy while maintaining safety. We look forward to continuing our clinical Phase III program of laquinimod, and hope it will offer enhanced quality of health for relapsing-remitting multiple sclerosis patients."

Source: Teva Pharmaceutical Industries and Active Biotech (29/06/09)

Teva Pharmaceutical Industries Ltd. and Active Biotech announced results from several new clinical and preclinical studies providing further insight on the immunomodulatory mechanism of action (MOA) of laquinimod, a novel oral once-daily compound being developed for the treatment of relapsing-remitting multiple sclerosis (RRMS).

Four sets of data being presented at the 61st Annual American Academy of Neurology Meeting (AAN) in Seattle stand to increase the understanding of how laquinimod may reduce multiple sclerosis activity and affect mechanisms related to disease pathology.

Research looking at the mechanism by which the compound exerts its clinical effect is ongoing; Current available data indicate that laquinimod impacts RRMS by modulating key processes of the immune system, and suggest an immunomodulating effect within the central nervous system (CNS).

“As we continue to study how laquinimod impacts multiple sclerosis, we remain encouraged by the potential of this oral candidate,” explains Scott Zamvil, M.D., Associate Professor, Department of Neurology University of California, San Francisco, “Laquinimod, with a balanced safety and efficacy profile, may address a currently unmet medical need for patients seeking effective oral therapy for multiple sclerosis that is also well tolerated and safe."

Laquinimod recently received Fast Track designation from the US Food and Drug Administration (FDA) which may allow the drug to enter the market as soon as late 2011. Teva completed enrollment for the first of its two Phase III clinical trials for laquinimod (ALLEGRO) in November 2008, and the second global Phase III study (BRAVO) is on schedule to complete patient enrollment in the first half of 2009.

ABOUT THE STUDIES
The studies evaluating the MOA of laquinimod being presented at AAN include:
• The effect of laquinimod on lymphocyte VLA-4 properties under shear flow conditions (Scientific session, April 30 from 1:30 PM – 3:30 PM, Room 605/610)
Liat Hayardeny, Sara Feigelson, Valentin Grabovsky, Joel Kaye, Rotem Keshet, Guy Cinamon, Ronen Alon, Netanya, Israel, Rehovot, Israel
o New data from this evaluation of a murine model suggest laquinimod selectively inhibits the chemokine-induced activation of T cell VLA-4 binding to VCAM-1, an endothelial cell adhesion molecule involved in T cell migration into the CNS. These data suggest a novel MOA of laquinimod.

• Down regulation of antigen presentation and inflammatory pathways by laquinimod in cultured peripheral blood mononuclear cells of untreated multiple sclerosis patients and healthy subjects (Poster session I, April 28 from 7:00 AM – 10:00 AM, Room 6E)
Rotem Or-Bach, Polina Sonis, Michael Gurevich, Anat Achiron, Ramat-Gan, Israel
o Data demonstrate laquinimod is intricately involved in the inflammatory response. Specifically, the early molecular events induced by laquinimod in RRMS patients were shown to potentially be the down regulation of MHC-class II gene transcription factors, the suppression of pro-inflammatory and cytokine related genes and the activation of an anti-inflammatory gene.

• Laquinimod Inhibits MOG-induced Experimental Autoimmune Encephalomyelitis (EAE) in CD4+CD25+ Regulatory T-cell Depleted Mice (Poster session VIII, April 30 from 11:30 AM – 2:30 PM, Room 6E)
Nora Tarcic, Emanuel Raymond, Joel Kaye, Netanya, Israel
o Results show laquinimod is effective in inhibiting disease severity with or without the presence of CD4+CD25+ cells, indicating the compound does not require this specific regulatory pathway. These findings further define its immunomodulatory effect.

• Effect of laquinimod on the Dendritic Cell compartment (Poster session I, April 28 from 7:00 AM – 10:00 AM, Room 6E)
Tal Birnberg, Steffen Jung, Rehovot, Israel
o Results from this additional murine study demonstrate that the effect of laquinimod on autoimmune deviation may also be due, in part, to its impact on the dendritic cell compartment, which is critical for the initiation and perpetuation of T cell-driven autoimmune disorders.

Source: Teva Pharmaceutical Industries Ltd.(29/04/09)

Teva Pharmaceutical Industries Ltd. and Active Biotech announced that oral laquinimod, an investigational treatment for relapsing-remitting multiple sclerosis (RRMS), has received a Fast Track designation from the U.S. Food and Drug Administration (FDA). Teva completed enrollment for the first of its two Phase III clinical trials for laquinimod (ALLEGRO) in November 2008 and is currently enrolling RRMS patients globally for the second Phase III study (BRAVO).

Drugs designated for Fast Track are intended for the treatment of a serious or life-threatening condition and have demonstrated the potential to address unmet medical needs. Fast Track designation can potentially facilitate development and expedite the review process. This may allow the drug to enter the market as soon as late 2011.

“As global leaders in the treatment of multiple sclerosis, Teva is committed to bringing additional safe, effective and convenient therapies to MS patients,” said Moshe Manor, Vice President, Global Innovative Resources Group at Teva Pharmaceutical Industries. “We are pleased that the FDA has awarded laquinimod with a Fast Track designation, and are hopeful it will be part of our growing portfolio of innovative therapies.”

“We're encouraged by the reports we've seen from the Phase II clinical trial of laquinimod, and if this agent continues to prove safe and effective, it would be a welcome new treatment option available to people with multiple sclerosis,” said Dr. John Richert, Executive Vice President, Research and Clinical Programs, National MS Society.

About Laquinimod

Laquinimod is a novel once-daily, orally administered immunomodulatory compound that is being developed as a disease-modifying treatment for RRMS. Active Biotech developed laquinimod and licensed it to Teva Pharmaceutical Industries, Ltd. in June 2004. Results from a Phase IIb study in 306 patients were published in June 2008 in The Lancet and reported that an oral 0.6 mg dose of laquinimod, administered daily, significantly reduced MRI disease activity by a median of 60 percent (51 percent mean reduction) versus placebo in RRMS patients. In addition, the study showed a favorable trend toward reducing annual relapse rates and in the number of relapse-free patients compared with placebo. Treatment was well tolerated, with some transient and dose-dependent increases in liver enzymes reported, without clinically-evident liver damage.

In addition to the efficacy that laquinimod has shown in Phase II RRMS clinical trials, laquinimod has demonstrated potent therapeutic efficacy in preclinical models of other autoimmune diseases such as Crohn’s disease, rheumatoid arthritis, insulin-dependent diabetes mellitus, Guillain Barré Syndrome, and Lupus. The broad profile of efficacy in animal models of inflammatory diseases suggests that laquinimod affects a pivotal pathway of inflammation and autoimmunity. Teva has also initiated a clinical study to evaluate laquinimod for Crohn’s disease and expects to initiate the clinical development of laquinimod for Lupus Nephritis in the near future.

About the Phase III Program

Allegro (assessment of oral laquinimod in preventing progression of MS), a pivotal, global, 24/30-month, randomized, double-blind, Phase III study designed to evaluate the efficacy, safety and tolerability of laquinimod versus placebo in the treatment of RRMS, completed recruitment of more than 1,000 patient at 152 sites throughout North America, Europe and Asia in November 2008.

Bravo (benefit-risk assessment of Avonex® and laquinimod), a pivotal, global, 24 month, randomized, double-blind, parallel-group, placebo-controlled Phase III study designed to compare the safety and efficacy of laquinimod with placebo and to provide risk-benefit data for laquinimod versus a currently available injectable treatment, is currently enrolling patients at centers throughout the United States, as well as Canada, Europe and Israel. The enrollment goal is approximately 1,200 patients with RRMS.

Source: Teva Pharmaceutical Industries Ltd.and Active Biotech (13/02/09)

Teva Pharmaceutical Industries Ltd. and Active Biotech  announced completion of patient enrollment for the Phase III clinical trial, Allegro, in relapsing-remitting multiple sclerosis (RRMS). The pivotal Allegro study is designed to evaluate the efficacy, safety and tolerability of the oral investigational compound, laquinimod, versus placebo in the treatment of RRMS.

The Allegro study completed patient screening at the end of the third quarter. Recruitment of over 1,000 patients at 152 sites throughout North America, Europe and Asia was finalized in November. The completion of recruitment triggers a milestone payment of $5 million to Active Biotech from Teva Pharmaceutical Industries Ltd.

A second pivotal Phase III clinical trial evaluating laquinimod, called Bravo, is currently enrolling patients globally. The Bravo trial aims to provide risk-benefit data for laquinimod versus Avonex®, an available injectable treatment.

Previous data from the phase IIb core study and its 36-week extension period (presented at the World Congress on Treatment and Research in MS in September) demonstrated the rapid onset and sustained efficacy of laquinimod in reducing disease activity, as well as the favourable safety profile of the compound.

About Laquinimod

Laquinimod is a novel once-daily, orally administered immunomodulatory compound that is being developed as a disease-modifying treatment for RRMS. Active Biotech developed laquinimod and licensed it to Teva Pharmaceutical Industries, Ltd. in June 2004. Results from a Phase IIb study in 306 patients were published in June 2008 in The Lancet and reported that an oral 0.6 mg dose of laquinimod, administered daily, significantly reduced MRI disease activity by a median of 60 percent (51 percent mean reduction) versus placebo in RRMS patients. In addition, the study showed a favorable trend toward reducing annual relapse rates and in the number of relapse-free patients compared with placebo. Treatment was well tolerated, with some transient and dose-dependent increases in liver enzymes reported, without clinically-evident liver damage.

In addition to the efficacy that laquinimod has shown in Phase II RRMS clinical trials, laquinimod has demonstrated potent therapeutic efficacy in preclinical models of other autoimmune diseases such as Crohn's disease, rheumatoid arthritis, insulin-dependent diabetes mellitus, Guillain Barré Syndrome, lupus and Inflammatory Bowel Disease. The broad profile of efficacy in animal models of inflammatory diseases suggests that laquinimod affects a pivotal pathway of inflammation and autoimmunity. Teva expects to initiate the clinical development of laquinimod for Crohn's disease and Lupus Nephritis in the near future.

About the Phase III Program

Allegro (assessment of oral laquinimod in preventing progression of MS) is a pivotal, global, 24/30-month, double-blind, Phase III study designed to evaluate the efficacy, safety and tolerability of laquinimod versus placebo in the treatment of RRMS.

Bravo (benefit-risk assessment of Avonex® and laquinimod) is a pivotal, multinational, multi-center, randomized, double-blind, parallel-group, placebo-controlled study designed to compare the safety and efficacy of laquinimod with placebo and to provide risk-benefit data for laquinimod versus a currently available injectable treatment. The enrollment goal is approximately 1,200 patients with RRMS.

The global clinical program will include centers throughout the United States as well as centers in Canada, Europe, and Israel.

Source: Teva Pharmaceutical Industries Ltd. and Active Biotech. (19/11/08)

Teva Pharmaceutical Industries Ltd. said new data from the extension phase of oral laquinimod in relapsing-remitting multiple sclerosis, or RRMS, demonstrated a significant reduction in the mean number of gadolinium-enhancing lesions in both patients who switched from placebo to laquinimod and patients who continued with their initial laquinimod dose.

Laquinimod is a novel once-daily, orally administered immunomodulatory compound that is being developed as a disease-modifying treatment for RRMS by Active Biotech, Sweden. Laquinimod is licensed to Teva Pharmaceutical.

The reduction was significant for both patients switching to high-dose and low-dose laquinimod. In addition, the proportion of patients who switched to active treatment from placebo, and remained enhancing lesion-free, increased from 31% to 47%, further reinforcing the efficacy of laquinimod on Magnetic Resonance Imaging measured disease activity.

Giancarlo Comi, University Vita-Salute San Raffaele, Italy, principal investigator of the study said, "With increased number of patients exposed to laquinimod, we found no new risks or safety issues. This reinforces earlier results demonstrating the laquinimod safety profile. The MS community looks forward to future data as we continue enrolling patients in the laquinimod Phase III clinical program."

Teva is currently enrolling patients for Allegro and Bravo, two pivotal Phase III clinical trials of laquinimod. The enrollment goal is approximately 1,000 patients with RRMS.

Source: RTT News © 2008 RTTNews (19/09/08)

BRAVO is a global, 24-month, double-blind study designed to evaluate the efficacy, safety and tolerability of the oral compound laquinimod versus placebo, and to provide risk-benefit data for laquinimod versus a currently available injectable treatment, Avonex® .

The BRAVO trial, which was initiated in April this year, aims to enroll approximately 1,200 patients with relapsing-remitting multiple sclerosis (RRMS). A second global Phase III trial of laquinimod including 1,000 patients, ALLEGRO, is also ongoing and recruiting patients globally. "All currently approved multiple sclerosis (MS) treatments are administered via injection or infusion. The ability to provide a safe and effective oral treatment option would be a significant advancement for the treatment of MS,” said Dr. Timothy Vollmer, Medical Director, Rocky Mountain MS Center, Denver, Colorado, and principal investigator of the BRAVO study. "Additionally, the mode of action for laquinimod is unlike any other MS compound, existing or experimental. We are hopeful that this research will expand our abilities to combat the disease through novel targeting.”

Data recently published in The Lancet demonstrated that oral dose of laquinimod significantly reduced the median magnetic resonance imaging (MRI) disease activity by 60 percent, compared to placebo and was well tolerated in RRMS patients. The majority of patients from the study are still receiving treatment with laquinimod in an open-label extension trial.

"The safety profiles of oral therapies are of increasing interest to the MS community; We are hopeful that laquinimod will be both efficacious and safe thus providing patients with an optimal risk-benefit profile,” said Dr. Per Soelberg Sorensen, Danish Multiple Sclerosis Research Center, Department of Neurology, Copenhagen University Hospital, and principal investigator of the BRAVO study.

Source: Die Welt © Die Welt (16/07/08)

Patients treated with laquinimod at a dose of 0.6 mg a day averaged 2.6 gadolinium-enhancing lesions on MRI compared with 4.2 for the placebo group (P=0.0048) as reported by Giancarlo Comi, M.D., of the University Vita-Salute and colleagues in the June issue of The Lancet.

The between-group difference emerged early in the trial, and follow-up beyond the primary study period demonstrated even larger reductions in MRI-detected lesions with laquinimod versus placebo.

Additionally, the number of new lesions was reduced by 50% in the laquinimod group.

"The decrease of MRI activity during the last part of the study was evidence for both gadolinium-enhancing and new T2 lesions, indicating that laquinimod reduces not only the extent of blood-brain barrier opening, but also the accrual of fixed lesions," the authors said.

Available therapies for multiple sclerosis all target inflammatory aspects of the disease. In addition, all of the approved therapies require injection, creating a potential advantage for any oral agent.

Laquinimod is structurally related to linomide, a drug that reduced disease activity in MS but had unacceptable toxicity, the authors said. Preclinical and phase I clinical studies suggested laquinimod had greater activity and a more favourable safety profile compared with linomide.

In a previous 24-week, randomized phase II study, laquinimod 0.3 mg/d suppressed formation of new MS lesions and was well tolerated. Those results led to the current evaluation of two different doses of the drug.

The study involved 306 patients relapsing-remitting multiple sclerosis with who had had one or more relapses in the previous year and at least one gadolinium-enhancing lesion on screening MRI. Investigators at 51 centers in nine countries randomized the patients to placebo or to laquinimod 0.3 mg/d or 0.6 mg/d.

The trial lasted 36 weeks, and the primary outcome was the cumulative total of gadolinium-enhancing lesions from the final four MRI scans at weeks 24, 28, 32, and 36.

Compared with placebo, laquinimod 0.6 mg reduced the average number of lesions per scan on the final four MRI scans by 40.4%.

The 0.3 mg dose did not significantly reduce the number of lesions compared with placebo (3.9 versus 2.6).

Comparison of the median cumulative number of lesions from the last four MRI scans resulted in a 55% reduction in the number of lesions with laquinimod 0.6 mg versus placebo (4.0 versus 9.0).

The number of new T2 lesions on the last four scans was 44% lower with laquinimod 0.6 mg (P=0.0013), and the number of new T1-hypointense lesions was 51% lower in the laquinimod 0.6 mg group (P=0.0064).

Examination of MRI scans from weeks 12 through 36 demonstrated a 51% reduction in the mean number of gadolinium-enhancing lesions with laquinimod 0.6 mg (2.7 versus 4.4) and a 60% decrease in the median number of lesions (6.0 versus 15.0).

Patients in the laquinimod 0.6 mg group had an annualized relapse rate of 0.52 compared with 0.77 for those on placebo which was not statistically significant (P=0.0978). Additionally, 70.8% of laquinimod 0.6 mg patients were relapse-free compared with 62.7% of the placebo group.

Both doses of laquinimod were well tolerated.  The primary treatment-related effect was a transient, dose-related increase in liver enzymes, the authors said.

Source: The Lancet - Comi G, et al "Effect of laquinimod on MRI-monitored disease activity in aptients with relapsing-remitting multiple sclerosis: a multicenter, randomized, double-blind, placebo-controlled phase IIb study" Lancet 2008; 371: 2085-2092. (20/06/08)

"Currently there are several RRMS treatments available; however, they are all administered via injection or infusion. An orally administered therapy brings us one step closer to offering patients and physicians a highly effective, new, convenient and less invasive method of drug delivery," said Doug Jeffery, M.D., Ph.D., Associate Professor, Wake Forest University Baptist Medical Center. "Previous Phase II studies have demonstrated positive results for laquinimod, and we hope that results from this pivotal Phase III trial will further reinforce these findings."

Recently, Teva concluded a 36-week extension of the 36-week Phase IIb core trial, which demonstrated that laquinimod 0.6 mg met its primary endpoint. The data from this extension trial further confirmed and strengthened the results from the initial 36-week Phase IIb trial. The majority of the patients that have participated in the trial are now receiving treatment with laquinimod in a continued open-label extension trial.

“The initiation of Phase III clinical trial is a critical milestone for Teva in our commitment to the MS community,” said Moshe Manor, Group Vice President - Global Innovative Resources, of Teva Pharmaceutical Industries Ltd. ”We are excited about the development of Laquinimod, which together with Copaxone, will broaden our MS platform and position Teva as a leading company in the MS field.”

Additional new data, presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) on October 13, 2007 in Prague, demonstrated that laquinimod reduced inflammation, demyelination and axonal damage in an animal model experimental autoimmune encephalomyelitis (EAE), indicating that the compound may have both anti-inflammatory and neuroprotective properties.

Based on encouraging results from various animal models, laquinimod is now being investigated for other autoimmune diseases.

“We are very pleased to see how Teva has successfully advanced the laquinimod clinical trial program in order to bring a novel, first-in-class product to the market for the treatment of MS,” said Sven Andréasson, President and CEO of Active Biotech AB.

The efficacy, safety, and tolerability of laquinimod will also be studied in an additional Phase III pivotal trial in RRMS (BRAVO), which is expected to begin enrollment in the first quarter of 2008. This trial is a multinational, multi-center, randomized, parallel-group, placebo-controlled study which will compare the effects of laquinimod to those of placebo, and provide risk-benefit data comparing once-daily orally administered laquinimod to a product presently used for treatment of RRMS (an active comparator). This study plans to enroll approximately 1,200 participants who will be followed for 24 months.

About Allegro

Allegro is a multinational, multi-center, randomized, double-blind, parallel-group, placebo-controlled study, currently enrolling approximately 1,000 patients with RRMS. The globally conducted study will include centers in the United States as well as centers throughout Canada, Europe, and Israel.

About Laquinimod

Laquinimod is a novel once-daily, orally administered immunomodulatory compound that is being developed as a disease-modifying treatment for RRMS. Active Biotech developed laquinimod and licensed it to Teva Pharmaceutical Industries, Ltd. in June 2004. A recent Phase IIb study in 306 patients was presented at the 2007 Annual Meeting of the American Academy of Neurology (AAN).

The data demonstrated that an oral 0.6 mg dose of laquinimod, administered daily, significantly reduced magnetic resonance imaging (MRI) disease activity by 40 percent versus placebo (p=0.0048) in RRMS patients, and was well tolerated. Looking into the median data of the primary end point laquinimod 0.6mg reduces disease activity (MRI) by 55% compared to placebo.

Laquinimod showed consistent and robust effect (statistical significant) on all secondary MRI end points. In addition, the study showed a favorable trend toward reducing annual relapse rates and the number of relapse-free patients compared with placebo. Treatment with both 0.3 and 0.6 mg doses were well tolerated with only some transient and dose-dependent increases in liver enzymes reported. To date 460 MS patients have received laquinimod in various clinical trials.

Source: Teva Pharmaceutical Industries Ltd.(07/11/07)

The companies are to commence two global Phase III trials of laquinimod during this year. The Phase III trials will take place in centers in the United States, Europe, and other locations worldwide, to further confirm the results of the Phase II trials.

“We are extremely excited about initiating the Phase III clinical program for oral laquinimod, as we believe laquinimod is a potential new and convenient treatment option for MS patients,” said Shlomo Yanai, President and CEO of Teva Pharmaceutical Industries Ltd. “The accelerated development of oral laquinimod is part of our commitment to MS patients to develop additional improved therapies that combine superior efficacy and excellent safety.”

“Laquinimod has the potential to be a novel, orally-administered disease modifying treatment for people suffering from multiple sclerosis,” said Sven Andréasson, President and CEO of Active Biotech. “Laquinimod would represent a milestone for patients as it would provide them with an efficacious and safe treatment, as well as a new drug delivery option that is suitable for long-term treatment.”

About Phase II Laquinimod Trials

Results from a 36-week, randomised, double-blind, placebo-controlled Phase IIb trial evaluating the effect of oral daily 0.3 and 0.6 mg doses of laquinimod on magnetic resonance imaging (MRI) -monitored disease activity in patients with RRMS were recently presented at the American Academy of Neurology (AAN) Annual Meeting in May, 2007. Data from the trial demonstrated that an oral 0.6 mg dose of laquinimod given daily significantly reduced MRI disease activity by 40 percent in RRMS patients and was well tolerated. In addition, there was a favorable trend towards reducing annual relapse rates, the number of relapse-free patients and time to first relapse compared with placebo. Treatment with both 0.3 and 0.6 mg doses of laquinimod were well tolerated with only some transient and dose-dependent increases in liver enzymes.

A previous 24-week Phase IIa trial conducted by Active Biotech demonstrated that oral 0.3 mg laquinimod given daily was well tolerated and reduced the formation of active lesions in RRMS.

About Laquinimod

Laquinimod is a novel once-daily, orally administered immunomodulatory compound that is being developed as a disease modifying treatment for multiple sclerosis (MS). Active Biotech developed laquinimod and licensed it to Teva Pharmaceutical Industries, Ltd. in June 2004. To date, 460 MS patients have received laquinimod in various clinical trials.

Source: Teva and Active Biotech (08/06/07)

Treatment with a 0.3 mg dose showed no statistical significant difference compared with placebo. "Current RRMS options are effective for the treatment of the disease, but an oral therapy such as laquinimod would represent a milestone for patients as it would provide them with a completely unique, non-invasive method of drug delivery," said Giancarlo Comi, MD, director of department of neurology and institute of experimental neurology, Universita Vita-Salute, San Raffaele, Milan, Italy.

"Preliminary studies have already demonstrated the positive effect of laquinimod versus placebo, but these new data confirmed that a higher dose was even more effective and remained well tolerated." The 36-week study evaluated the effect of oral daily 0.3 and 0.6 mg doses of laquinimod on MRI-monitored disease activity in patients with RRMS. The majority of the patients who participated in the study continued treatment with laquinimod in an ongoing, blinded 9 month extension study. This extension study is followed by an open label study where patients will receive 0.6 mg laquinimod for an additional 24 months.

"The results of this study, which once again demonstrate the efficacy and tolerability of once-daily oral laquinimod, are very exciting for the MS community both patients and researchers," said Shlomo Yanai, president and CEO of Teva Pharmaceutical Industries Ltd. "Teva will soon initiate phase III studies to confirm oral laquinimod's therapeutic benefits, and we expect to begin enrolment of the trial later this year."

Source: Pharmabiz.com Copyright © Saffron Media Pvt. Ltd.(05/05/07)

Teva Pharmaceutical Industries Ltd and Active Biotech AB today announced that a Phase IIb study designed to evaluate the safety and efficacy of laquinimod, a once-daily novel oral agent, in relapsing remitting multiple sclerosis (MS) patients, met its primary end-point.

Laquinimod treatment significantly reduced the rate of inflammatory disease activity, as measured by the cumulative number of Gadolinium enhancing lesions on brain MRI scans after 36 weeks of treatment. Laquinimod treatment also demonstrated a considerable reduction in the number of clinical relapses compared to placebo. This Phase IIb multi-center, randomized, double-blind, placebo-controlled study enrolled approximately 300 patients in 8 European countries and in Israel.

The evaluation of the safety and side-effect data confirmed the favourable safety profile that was seen in earlier phase II clinical trials. The majority of the patients who participated in the study are currently continuing treatment with laquinimod in an ongoing, blinded extension study.

"The study results with once daily oral laquinimod are very encouraging and further demonstrate our ongoing commitment to developing new classes of therapies for MS, including oral therapies, to treat the disease, as well as to improve the patients' quality of life", said Israel Makov, President and CEO of Teva Pharmaceutical Industries Ltd.

"As of today, nearly 400 patients have received laquinimod in various clinical trials over the last years. The data from the completed studies together with preclinical documentation, confirm laquinimod's efficacy and favorable safety profile in MS patients," said Sven Andreasson, President and CEO of Active Biotech AB.

The positive result of the clinical trial triggers a milestone payment to Active Biotech.

Further details about the study will be given at Teva's Innovative R&D Day in New York City on September 26th, 2006. A complete presentation of the Phase IIb data will be given at upcoming relevant scientific meetings.

Teva is discussing laquinimod's development plan with regulatory authorities in order to accelerate the clinical program into Phase III.

About Laquinimod

Laquinimod is a novel once-daily, orally administered immunomodulatory compound developed as a disease modifying treatment for multiple sclerosis (MS). Active Biotech developed laquinimod and licensed it to Teva Pharmaceutical Industries Ltd. in June 2004.

Source: Teva Pharmaceutical Industries Ltd

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