Multiple Sclerosis Resource Centre
  • Home
  • About MS
  • MSRC Services
  • Get Involved
  • MS Research News
  • MSRC Groups
  • Useful Resources
  • Welcome To Josephs Court, MS Centre Of Excellence
  • Advertising
  • E-Newsletter
  • Contact Us
  • Cookie Policy
  • Investor in People
    You are here : Home » MS Research News » Drugs » MN-166 (Ibudilast)

    MN-166 (Ibudilast)

    A A A
    [Print this page]

    Share |


    MN-166 is an orally administered drug with a novel mechanism of action that includes the inhibition of leukotriene activity, phosphodiesterases and nitric oxide synthase.

    Ibudilast awarded patent for treating progressive multiple sclerosis in Europe

    Medicinova LogoBiopharmaceutical company MediciNova Inc reported on Thursday the receipt of a Notice of Allowance from the European Patent Office for an application covering the use of ibudilast for progressive forms of multiple sclerosis (MS), a chronic disease in which disability progresses over time.

    According to the company, ibudilast (MN-166) is its drug development candidate for certain neurological conditions, including primary progressive or secondary progressive MS, drug addiction and pain.

    The company's patent maturing from this allowed patent application is expected to expire no earlier than early 2029 and covers a method of treating progressive MS.

    Additionally, the company's clinical investigations showed an apparent disease-modifying benefit in which brain volume loss, or brain atrophy, commonly associated with disease progression, was reduced by oral administration of ibudilast to a group of MS patients in a dose-related fashion over a ten month period.

    Source: MENA.FM.COM © 2000 menafn.com (26/10/12)

    MediciNova to receive US patent for method of treating progressive MS

    Medicnova LogoMediciNova Inc, a biopharmaceutical company, has received a Notice of Allowance from the US Patent and Trademark Office for a pending patent application, which covers the use of ibudilast for the treatment of progressive forms of multiple sclerosis.

    Ibudilast (MN-166), is the company's lead drug development candidate for certain neurological conditions, including progressive multiple sclerosis, neuropathic pain, and drug addiction.

    A patent maturing from this allowed patent application is expected to expire no earlier than early 2029 and covers a method of treating primary progressive multiple sclerosis (PPMS) or secondary progressive MS (SPMS) by administering ibudilast either alone or in combination with other drugs.

    The patent application is based upon clinical investigations conducted by MediciNova researchers which showed an apparent disease-modifying benefit in which brain volume loss, or brain atrophy, commonly associated with disease progression, was reduced by oral administration of ibudilast to a group of multiple sclerosis patients including some subjects with progressive multiple sclerosis, in a dose-related fashion over at least a 10-month treatment period.

    Multiple sclerosis (MS) is recognized as a chronic disease in which disability progresses over time. Patients suffering from progressive forms of MS tend to have a poor prognosis and have greater levels of disability. Robert J. Fox, M.D., M.S., FAAN, medical director of Mellen Center for MS, Cleveland Clinic, noted that, "Despite recent improvements in pharmacotherapy for relapsing remitting multiple sclerosis, treatment options in progressive multiple sclerosis are extremely limited in the absence of relapses. There is great need for safe, effective, and conveniently-administered therapies for progressive MS."

    Obtaining long-term protection of market exclusivity for the use of ibudilast in certain neurological conditions has been a key component of MediciNova's development strategy for the MN-166 program. Yuichi Iwaki, M.D., Ph.D., president and chief executive officer of MediciNova, noted that, "We are very pleased to receive notice of this patent allowance for ibudilast in progressive MS. Moreover, we anticipate that this allowance will facilitate further development and business options around this program."

    Ibudilast has been used in asthma and post-stroke disorders in Japan for around 20 years. MediciNova has demonstrated the potential utility of ibudilast in the treatment of neurological disorders at higher doses with encouraging outcomes in company-sponsored clinical trials in multiple sclerosis (MS) and neuropathic pain. MediciNova's collaborative trial planning with drug addiction investigators at organizations like Columbia/NYSPI and UCLA has led to National Institute on Drug Abuse (NIDA)-to support clinical investigations of the use of ibudilast to treat both opioid and methamphetamine addiction.

    A phase 2 investigator-sponsored trial of ibudilast in the treatment of chronic medication overuse headache (MOH) pain is also ongoing in Australia. MediciNova's priorities include pursuing Phase 2 proof-of-concept trials of ibudilast for the treatment of progressive MS and/or neuropathic pain through non-dilutive funding.

    Source: Pharmabiz.com Copyright © 2012 Saffron Media Pvt. Ltd (06/02/12)

    Ibudilast in relapsing-remitting multiple sclerosis. A neuroprotectant?

    MS MRIBACKGROUND: Ibudilast is a phosphodiesterase inhibitor influencing inflammation and neurodegeneration in multiple sclerosis (MS).

    This study evaluated the safety, tolerability, and effects on MRI parameters of 2 different doses of ibudilast in relapsing forms of MS.

    METHODS: In this multicenter, double-blind, phase 2 trial, patients with relapsing MS and gadolinium-enhancing lesions were randomly assigned 1:1:1 to receive 30 or 60 mg ibudilast or placebo every day for 12 months. The primary endpoint was the cumulative number of newly active lesions on bimonthly brain MRI over 12 months. Secondary endpoints included relapse rate, change in Expanded Disability Status Scale (EDSS) score, T2-hyperintense and T1-hypointense lesion volumes, and percent brain volume change (PBVC).

    RESULTS: A total of 297 patients were randomized in 19 centers. During the first 12 months, the mean number of active lesions and relapse rate did not differ between treatment arms. A reduction in PBVC (p = 0.04) was found in the 60-mg group (0.8%) compared with placebo (1.2%). Post hoc analysis showed a reduction in the proportion active lesions that evolved into persistent black holes for the 60-mg (0.14; p = 0.004) and 30-mg (0.17; p = 0.036) groups compared with the placebo group (0.24). Over 2 years, there were fewer patients (p = 0.026) with confirmed progression on the EDSS. Treatment with ibudilast was generally safe and well tolerated.

    CONCLUSION: Ibudilast showed no beneficial effect on the rate of newly active lesions and relapses. However, preliminary evidence suggests that ibudilast seems to act in a neuroprotective fashion as measured by 2 independent MRI outcomes, with a possible beneficial clinical effect on disability progression. Classification of evidence: This interventional study provides Class III evidence on the effect of ibudilast on disease activity.

    Barkhof F, Hulst HE, Drulovic J, Uitdehaag BM, Matsuda K, Landin R; For the MN166-001 Investigators.

    From the Image Analysis Center (F.B., H.E.H.) and MS Centre (B.M.J.U.), VU University Medical Center, Amsterdam, The Netherlands; Kliniki Centar Srbije (J.D.), Institut za Neurologiju Beograd, Serbia; and Medicinova Inc. (K.M., R.L.), San Diego, CA.

    Source: Pubmed PMID: 20200338 (17/03/10)

    Data from two-Year phase II MN-166 clinical trial in Multiple Sclerosis presented at WCTRIMS

    Medicnova Logo

    Data from the completed two-year Phase II clinical trial of orally administered MN-166 for the treatment of multiple sclerosis (MS) was presented in two poster presentations at the World Congress for Treatment and Research in MS being held in Montreal, Canada.

    The first presentation entitled "Clinical Effect of the Neuroprotectant MN-166 in Relapsing Forms of MS: Year 2 Data" (Poster 48), given by Dr. Richard Gammans, Chief Development Officer of MediciNova, reported that MN-166 treatment resulted in positive findings on three independent measures indicative of a potential disease-progression modifying effect. The poster can be accessed at: http://www.medicinova.com/MN-166-Relapsing-MS.html. The findings include:


     * Sustained disability progression was significantly less likely (by
       approximately 50 percent) in those patients receiving MN-166 at
       either 30 or 60 mg per day for 24 months than in those patients
       receiving the drug for 12 months (p=0.026).  Sustained disability
       progression was measured as a greater than or equal to 1.0 point
       increase from baseline in the Expanded Disability Status Scale
       (EDSS) score for four consecutive months. This positive clinical
       finding was corroborated by positive findings on two separate
       radiologic measures.

     * The Phase II clinical trial demonstrated that the significant
       reduction in brain volume loss (p=0.035), as measured by cranial
       magnetic resonance imaging (MRI) scans, observed after 12 months
       in patients treated with 60 mg per day of MN-166 compared to
       placebo was again demonstrated in year two of the study. Brain
       volume loss was significantly less (p=0.030) in patients who
       received 60 mg per day of MN-166 for 24 months compared to the
       other treatment groups.


    The second presentation entitled "Ibudilast Reduces Conversion of New Inflammatory Lesions to Persistent Black Holes in Active Relapsing Multiple Sclerosis" (Poster 271), given by Dr. Hanneke Hulst of VU University Medical Center, Amsterdam, The Netherlands, reported that the Phase II data demonstrated that MN-166 treatment resulted in positive findings on independent MRI measures indicative of a neuroprotective effect. The findings include:


     * MN-166 treatment at 60 mg per day significantly reduced the
       relative risk for conversion of new inflammatory lesions identified
       at month two to Persistent Black Holes (PBH), an MRI indicator of
       neuronal loss, eight months later at month ten by 37 percent
       (p=0.011); such lesions that remain unchanged for eight months are
       considered PBHs as compared to transient inflammatory lesions that
       are more closely associated with relapses.  MN-166 treatment at 30
       mg per day resulted in a trend toward reducing evolution to PBH
       (p=0.074).  Loss of brain volume and development of PBHs on MRI
       have been shown to correlate with clinical progression and
       disability in MS patients.

    "We are pleased that the WCTRIMS Scientific Program Committee accepted two presentations on different aspects of the results from our recently completed Phase II clinical trial of MN-166," said Yuichi Iwaki, M.D., Ph.D., President and Chief Executive Officer of MediciNova, Inc. "The significant favorable effects on measures of disability progression and reduced neuronal damage observed in the study, as described in these presentations, are quite exciting and representative of the type of new treatment being sought by the MS scientific community according to our advisors. We are excited to be part of advancing MS treatment in a new direction and look forward to confirming these findings in future clinical trials with the assistance of a corporate partner."

    The two-year randomized, double-blind, placebo-controlled Phase II clinical trial included 297 patients with relapsing MS. In the second year of the study, all patients were on drug. Patients who received 30 or 60 mg of MN-166 per day during the first 12 months of the study remained on the assigned dose for the second 12 months of the study; patients who received placebo during the first 12 months of the study were randomized to receive either 30 or 60 mg of MN-166 per day (double-blind maintained) during the second 12 months of the study. Clinical and radiological outcomes were evaluated.
    MN-166 was well tolerated at all doses over the 24 months of this Phase II clinical trial. Of the 297 patients enrolled in the study, 82.5 percent, or 245 patients, completed the full 24 months of the study. The most common adverse events possibly related to MN-166 included mild, transient gastrointestinal disturbances and depression.

    First-year efficacy results of this clinical trial were announced in March 2007 and described more completely at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting in November 2007. Clinical results from the completed two-year clinical trial were announced in April 2008.

    Source: MediciNova, Inc (19/09/08)

    MediciNova Reports Clinical Results From Two-Year Phase II Clinical Trial of MN-166 in Multiple Sclerosis
    MN-166 Slows Disability Progression; Significant Neuroprotective Effects Observed by MRI.

    MediciNova, Inc. today announced positive clinical findings from the completed two-year Phase II clinical trial of orally administered MN-166 for the treatment of multiple sclerosis (MS). The second year findings expand upon the results from the first year of this study reported previously.

    MN-166 treatment resulted in positive findings on three independent measures indicative of a potential disease-progression modifying effect. The findings include:

    • Sustained disability progression was significantly less likely (by approximately 50 percent) in those patients receiving MN-166 at either 30 or 60 mg per day for 24 months than in those patients receiving the drug for 12 months (p=0.026). Sustained disability progression was measured as a greater than or equal to 1.0 point increase from baseline in the Expanded Disability Status Scale (EDSS) score for four consecutive months. This positive clinical finding was corroborated by positive findings on two separate radiologic measures.
    • The clinical trial demonstrated that the significant reduction in brain volume loss (p=0.035), as measured by cranial magnetic resonance imaging (MRI) scans, observed after 12 months in patients treated with 60 mg per day of MN-166 compared to placebo was again demonstrated in year two of the study. Brain volume loss was significantly less (p=0.030) in patients receiving 60 mg per day of MN-166 for 24 months compared to the other treatment groups (for more information on Percent Brain Volume loss for each of the treatment groups in year two of the study.
    • MN-166 treatment at 60 mg per day significantly reduced the relative risk for conversion of new inflammatory lesions identified at month two to Persistent Black Holes (PBH), an MRI indicator of neuronal loss, eight months later at month ten by 37 percent (p=0.011); such lesions that remain unchanged for eight months are considered PBHs as compared to transient inflammatory lesions that are more closely associated with relapses. MN-166 treatment at 30 mg per day resulted in a trend toward reducing evolution to PBH (p=0.074). Loss of brain volume and development of PBHs on MRI have been shown to correlate with clinical progression and disability in MS patients.

    MN-166 was well tolerated at all doses over the 24 months of this clinical trial. Of the 297 patients enrolled in the study, 82.5 percent, or 245 patients, completed the full 24 months of the study. The most common adverse events possibly related to MN-166 included mild, transient gastrointestinal disturbances and depression.

    "After an extensive review of these data our Scientific Advisory Board recommended that MN-166 be advanced into pivotal-design studies with clinical and MRI evaluations of MS progression as the primary objectives," said Yuichi Iwaki, M.D., Ph.D., President and Chief Executive Officer of MediciNova, Inc. "The significant favorable effects on measures of disability progression and reduced neuronal damage observed in this study are quite exciting and representative of the type of new treatment being sought by the MS scientific community according to our advisors. We are excited to be part of advancing MS treatment in a new direction and look forward to confirming these findings in future clinical trials with the assistance of a corporate partner."

    The two-year randomized, double-blind, placebo-controlled Phase II clinical trial included 297 patients with relapsing MS. In the second year of the study, all patients were on drug. Patients who received 30 or 60 mg of MN-166 per day during the first 12 months of the study remained on the assigned dose for the second 12 months of the study; patients who received placebo during the first 12 months of the study were randomized to receive either 30 or 60 mg of MN-166 per day (double-blind maintained) during the second 12 months of the study. Clinical and radiological outcomes were evaluated.

    First-year efficacy results of this clinical trial were announced in March 2007 and described more completely at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting in November 2007. Briefly, MN-166 at 60 mg per day significantly reduced brain volume loss by 33 percent and median time to first relapse by 157 days compared to placebo. The median time to first on-study relapse was 244 days for placebo, 255 days on MN-166 at 30 mg per day and 401 days (which could only be calculated after the full study unblinding) on MN-166 at 60 mg per day. MN-166 did not significantly reduce cumulative brain lesion count on MRI in year one of this clinical trial, which was the protocol-defined primary endpoint of the study.

    About MN-166

    MN-166 is a novel, orally administered compound being evaluated for the treatment of MS. MN-166 increases the release of neuronal growth factors and inhibits leukotriene activity, phosphodiesterases and nitric oxide synthase. MN-166 may also suppress the production of pro-inflammatory cytokines (IL-1beta, TNF-alpha) and may enhance the production of the anti-inflammatory cytokines (IL-4, IL-10).

    MediciNova acquired an exclusive, worldwide (excluding Japan, China, Taiwan and South Korea), sublicensable license to MN-166 for the treatment of MS, excluding ophthalmic solution formulations, from Kyorin Pharmaceutical Co. Ltd. For the past 18 years, MN-166 has been marketed in Japan and South Korea as Ketas(r) for the treatment of asthma and cerebrovascular disorders. Data from the existing clinical trial and post-marketing surveillance databases, which includes treatment of an estimated 3.2 million patients with these disorders, indicate that Ketas(r) is well tolerated.

    Source: MediciNova, Inc. (07/04/08)

    MediciNova's MN-166 Reduces Persistent Black Hole Formation in Multiple Sclerosis Patients
    MediciNova, Inc today announced additional data from a double-blind analysis of the first year of treatment from its two-year Phase II clinical trial of MN-166 in multiple sclerosis (MS). The second year of the Phase II clinical trial is on-going with results expected in April 2008. The analysis showed that MN-166 decreased the formation of black holes (permanent brain lesions believed to indicate the death of nerves in the brain) on magnetic resonance imaging (MRI) in MS patients, adding support to MediciNova's belief that MN-166 may provide neuroprotection in relapsing MS.

    Data demonstrated that a 60 mg/day dosing regimen of MN-166 significantly reduced the proportion of new T1 gadolinium-enhancing or new T2 lesions identified at month two of the study that evolved into persistent black holes at month 10 compared to placebo (RR 0.63, p=0.011). Treatment with a 30 mg/day dosing regimen of MN-166 showed a trend toward reduced risk of new lesion evolution to persistent black holes compared to placebo (RR 0.735, p=0.074).

    "The results of this new analysis provide further evidence of a potential neuroprotective effect of MN-166 in MS patients and are consistent with the previously announced results showing that 60 mg/day of MN-166 significantly attenuated percent brain volume loss compared to placebo treatment during the first year of this study," said Dr. Frederik Barkhof, Professor of Neuroradiology, Vrije Universiteit Medical Centre (VUMC), Amsterdam, The Netherlands.

    The evaluation was performed using MRI data collected from 292 patients with relapsing forms of MS who were randomly assigned to receive daily oral treatment with placebo or 30 or 60 mg/day of MN-166 during year one of this two year study. MediciNova's Scientific Advisory Board suggested this evaluation to further elucidate the mechanism by which MN-166 significantly reduced the percent of brain volume loss observed in year one. MRIs were collected bimonthly during the one year treatment period and were re-evaluated in a double-blind manner for this new analysis. Predefined endpoints for this evaluation were the rate of evolution of new lesions to persistent black holes and remyelinated lesions. New T1 gadolinium-enhancing or new T2 lesions were defined as new lesions in the first on-study MRI at month two and tracked in the month four and month 10 MRIs. Lesions were classified at month 10 as persistent black holes or remyelinated lesions according to predefined criteria. The relative risk (RR) of new lesion evolution to persistent black holes and remyelinated lesions per patient was analyzed using a generalized linear statistical model.

    Of the 292 patients who received either placebo (n=100), 30 mg/day of MN-166 (n=94) or 60 mg/day of MN-166 (n=98), 72 of the placebo-treated patients, 64 of the patients receiving 30 mg/day of MN-166 and 56 of the patients receiving 60 mg/day of MN-166 had new lesions in month two. The proportions of new lesions evolving to persistent black holes were 0.24, 0.20 and 0.16 in the placebo, 30 mg/day of MN-166 and 60 mg/day of MN-166 treatment groups, respectively. The RR for new lesion evolution to persistent black holes was significantly lower (RR 0.63, p=0.011) in MS patients treated with 60 mg/day of MN-166 and tended to be lower (RR 0.735, p=0.074) in patients treated with 30 mg/day of MN-166 compared to placebo-treated patients. The proportion of new lesions that evolved to remyelinated lesions did not differ significantly among treatments.

    About MN-166

    MN-166 is a novel, orally administered compound being evaluated for the treatment of MS. MN-166 inhibits leukotriene activity, phosphodiesterases and nitric oxide synthase, all inflammatory mechanisms known to be involved in MS. MN-166 may also suppress the production of pro-inflammatory cytokines (IL-1?, TNF-?) and may enhance the production of the anti-inflammatory cytokines (IL-4, IL-10). Clinical results showing positive clinical benefits and the drug to be well tolerated after one year of treatment in this two-year randomized, double-blind, placebo-controlled Phase II clinical trial in 297 relapsing multiple sclerosis patients were reported in March 2007. The second year of this clinical trial is ongoing with results expected in April 2008.

    MediciNova acquired an exclusive, worldwide (excluding Japan, China, Taiwan and South Korea), sublicensable license to MN-166 for the treatment of MS, excluding ophthalmic solution formulations, from Kyorin Pharmaceutical Co. Ltd. For the past 18 years, MN-166 has been marketed in Japan and South Korea as Ketas(r) for the treatment of asthma and cerebrovascular disorders. Data from the existing clinical trial and post-marketing surveillance databases, which includes treatment of an estimated 3.2 million patients with these disorders, indicate that Ketas(r) is well tolerated.

    Source: MediciNova, Inc (01/02/08)

    MN-166 (Ibudilast) Shows Efficacy in Relapsing Forms of Multiple Sclerosis
    The anti-inflammatory and neuroprotective oral agent MN-166 (ibudilast) shows an excellent safety profile at 60 mg/day and provides significantly prolonged time-to-first relapse and attenuated brain volume shrinkage in patients with relapsing-remitting (RR) and/or secondary progressive (SP) multiple sclerosis (MS).

    Sponsor trial coordinator Richard E. Gammans, PhD, Chief Development Officer, MediciNova Inc., San Diego, California, presented the findings from a multicenter, randomised, double-blind, placebo-controlled, phase 2 study here on October 12 at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

    "Pharmacologically, MN-166 has mechanisms that include anti-inflammatory effects, such as phosphodiesterase inhibition, and neuroprotective effects, such as inhibition of [nitric oxide] synthesis and reduction in reactive oxygen species," he said. This study was thus designed to evaluate the effects of MN-166 in patients with MS.

    The study enrolled patients aged 18 to 55 years who were diagnosed with RRMS or SPMS using McDonald criteria, with continued relapses. They had one or more Gd-enhancing lesion on MRI scan taken 2 weeks before treatment start; and expanded disability status scale (EDSS) no greater than 5.5 at screening. The main exclusion criteria were based around no use of various immunosuppressants within 6 months, or of interferons -- corticosteroids and adrenocorticotropic hormone -- within 45 days of the initial magnetic resonance imaging (MRI) scan.

    The primary endpoint was cumulative active lesions on MRI. The secondary endpoints were clinical relapse and other MRI measures.

    Of 967 patients screened, 100 were randomized to placebo, 94 were randomized to 30 mg/day of MN-166, and 96 were randomized to 60 mg/day of MN-166 for the first 12 months of treatment, with clinical and MRI evaluations every 2 months. The 12-months extension phase was designed to evaluate the effects of continuation of MN-166 dosing, with placebo patients switched to MN-166 30 mg/day or 60 mg/day.

    Baseline clinical characteristics across these three treatment groups were similar for percent RRMS, percent spinal or cerebrum location of lesions, and number of relapses in previous 24 months. There were indications that time since both MS diagnosis and onset of symptoms were longer in the treated groups (39, 50, 60 months; 73, 96, 98 months; respectively).

    In terms of primary outcome of cumulative active lesions over the first 12 months, there was no significant difference amongst treatments. However, there was a modest difference between the highest dose of MN-166 and placebo, with an 18% reduction in cumulative active lesions, although this difference was not significant, indicated Dr. Gamman.

    Similarly, there were no significant differences between treatment group in the percent of patients with sustained disability progression on EDSS (8.0%, 5.3%, 4.1%).

    In contrast, for other MRI assessments over the 12 months, MN-166 at 60 mg/day showed not only a significant improvement in the percentage of brain volume reduction (P =.035), but also a significant increase in the median time to first relapse (P =.04). Thus, the percentage of patients who were relapse-free at year 1 was significantly greater at the higher MN-166 dose (41% vs 41.5% vs 56.0% (P =.03).

    Dr. Gammans said that MN-166 was very well tolerated, with 89% of patients completing the first 12 months of treatment. "The side effects were generally mild, and resolved without intervention, and there were no adverse observations on laboratory or [electrocardiographic] findings as well," he added.

    When the two MN-166 treatment groups were combined, gastrointestinal side effects were the only adverse events to occur at 2-fold or greater times those of placebo (7.6% vs 14.7% vs 22.2%), although tolerance to these effects occurred rapidly (2-4 days). There were no deaths in the study.

    Due to these modest effects of MN-166 on inflammatory lesion counts and based on its pharmacology, Dr. Gamman said that the clinical benefits of MN-166 60 mg/day arise primarily from its actions towards protection of neurons from damage, rather than towards reduction of inflammatory lesions.

    At the same time, the excellent safety profile at 60 mg/day and the effects that reached significance in this study suggest that future studies with MN-166 should evaluate higher doses on disease progression and MRI measures of neuroprotection, rather than inflammation.

    Funding for this study was provided by MediciNova Inc.

    Source: Presentation title: Clinical Effect of the Neuroprotectant MN-166 in Relapsing Forms of MS. Abstract 52 (15/10/07)

    MediciNova Announces New Strategic Initiative

    MediciNova, Inc., a biopharmaceutical company today announced that based on recent clinical successes and evaluation of market opportunities, it will focus its resources on development and commercialisation of two key assets in its development pipeline, MN-221 and MN-166. MediciNova believes that MN-221, now in Phase IIa clinical testing, has the potential to become the new standard of care for the treatment of severe, acute exacerbations of asthma (status asthmaticus) in emergency facility settings.Data from the Phase IIa trial is expected during the fourth quarter of 2007.

    MN-166, an oral treatment for multiple sclerosis, demonstrated positive clinical benefits and a superior safety profile after one year of treatment in a two-year randomised, double-blind, placebo-controlled Phase II trial in 297 relapsing multiple sclerosis patients.

    Adhering to its strategy to focus investment on key assets such as MN-221 and MN-166, and in order to bring these assets substantially forward towards commercialisation, MediciNova will limit its expenditures on other development programs to only those activities necessary to maximise each asset's value, while aggressively pursuing a variety of initiatives to monetise these development programs. As part of this strategy, MediciNova will discontinue development of MN-001 in its current immediate-release formulation. As such, the current Phase III trial of MN-001 in bronchial asthma patients will be stopped. To date, approximately 200 patients have been enrolled in that trial with no reported serious adverse events. The formulation currently being tested requires a multiple dosing per day schedule. Market and competitive analyses point to the desire for a once-a-day therapy for bronchial asthma and, thus, MediciNova will continue its work on developing a once-a-day preparation of MN-001. MediciNova anticipates that this reallocation of resources will provide substantial cash savings over the next 12 months.

    "MediciNova's strategy has always been to select and develop product candidates that fill an unmet medical need and offer competitive market advantages. To that end, we have built an attractive pipeline that provides us with multiple opportunities from which to realise value," said Yuichi Iwaki, M.D., Ph.D., President and Chief Executive Officer of MediciNova, Inc. "In focusing our resources, we are in the enviable position to dedicate investment to two commercially attractive development candidates that we can potentially commercialise on our own with a small, focused sales force, while we simultaneously continue efforts to monetise the remainder of our pipeline through business development initiatives, including potential partnering opportunities. We believe this new strategy will provide even greater value in the realization of our key clinical assets."

    Source: MediciNova, Inc (26/06/07)

    MediciNova Announces Positive Clinical Results From MN-166 Phase II Multiple Sclerosis Trial
    MediciNova, Inc., today announced positive clinical findings from the 12-month core period of a Phase II clinical trial of MN-166 that measures both surrogate (radiological) and clinical outcomes over two years of treatment in 297 patients with relapsing multiple sclerosis (MS).

    The randomised, double-blind, placebo-controlled trial showed a significant increase in the proportion of patients who remained relapse-free over the first 12 months of treatment with 60 mg per day of MN-166 compared to placebo (p=0.03). The time to first relapse was also significantly increased in patients treated with 60 mg of MN-166 per day compared to placebo (p=0.04). Positive trends were also observed in the annualised relapse rate (p=0.08) and number of relapses (p=0.10) among patients who completed the full first 12 months of treatment with 60 mg of MN-166 per day compared to those patients completing the first 12 months of treatment on placebo.

    A significant reduction in brain volume loss (p=0.04), as measured by cranial magnetic resonance imaging (MRI) scans, was observed in patients treated with 60 mg per day of MN-166 compared to placebo. Loss of brain volume on MRI has been shown to correlate with clinical progression and disability in MS patients. Positive trends were also observed in several other radiological outcome measures, including the volume of gadolinium-enhancing (T1) lesions (p=0.09) in patients treated with 60 mg of MN-166 per day compared with placebo. However, no reduction in the cumulative number of active (gadolinium-enhancing (T1) and non-enhancing new/enlarging (T2)) lesions on cranial MRI scans over 12 months of treatment was observed in patients treated with MN-166 compared to placebo, which was the protocol-defined primary endpoint of the study. No clinical or radiological benefit was observed in patients treated with 30 mg per day of MN-166. MN-166 was well tolerated at all doses in this trial. Eighty-nine percent of patients completed the first 12 months of the trial with only mild gastrointestinal side effects observed with MN-166 compared to placebo (3-6% vs. 1-3%, respectively).

    The independent Data Safety Monitoring Board (DSMB) has recommended that the trial continue beyond the first year of treatment without modification and was supportive of further clinical evaluation of MN-166 in MS patients.

    "We are pleased with the benefit of MN-166 observed in MS patients in this trial; they confirm the results of previous pilot trials of MN-166 in MS patients conducted by Japanese academic investigators," said Yuichi Iwaki, M.D., Ph.D., Executive Chairman and CEO of MediciNova, Inc. "The divergence of clinical benefit and radiological findings suggest that MN-166 may be acting by a different mode of action than current treatments. We will carefully analyse the clinical data with our independent advisors to determine next steps in the development program and to advance this compound into Phase III clinical testing."

    In July 2005, MediciNova initiated a randomised, double-blind, placebo-controlled multi-center Phase II clinical trial of MN-166 in MS patients in five Eastern European countries. A total of 297 patients with at least one gadolinium-enhancing lesion on a screening visit MRI scan were randomised to receive placebo or one of two doses of MN-166 (30 or 60 mg per day) in this trial. Safety and efficacy assessments were performed at months 1, 2, 4, 6, 8, 10 and 12 of the trial. Efficacy assessments were based on the evaluation of the cumulative number of active (gadolinium-enhancing (T1) and non-enhancing new/enlarging (T2)) cranial MRI lesions (the primary endpoint of the trial) and other MRI-related, exacerbation and disability-related endpoints (relapse rate and Expanded Disability Status Scale (EDSS) score) after 12 months of treatment. Eligible patients who elected to continue their participation in the trial after 12 months of treatment will continue to receive treatment and will be assessed at months 13, 14, 16, 18, 20, 22 and 24 of the trial; patients who received placebo during the first 12 months of the trial were randomised to receive either 30 or 60 mg of MN-166 per day (double-blind maintained) during the second 12 months of the trial.

    Source: PrimeNewsWire © 2006 PrimeNewswire All Rights Reserved.(27/03/07)

    MediciNova Announces Completion of Enrollment in a Phase II Multiple Sclerosis Trial With MN-166
    MediciNova, Inc., a specialty pharmaceutical company, today announced completion of enrollment of 297 patients with relapsing remitting multiple sclerosis (MS) in its Phase II clinical trial of MN-166.

    MN-166 is a novel, orally administered compound being evaluated for the treatment of MS. In July 2005, MediciNova initiated a randomized, double-blind, placebo-controlled multi-center Phase II clinical trial of MN-166 in MS patients in Eastern Europe. Two hundred and ninety-seven (297) patients have been randomized to receive placebo or one of two doses of MN-166 in this trial. Efficacy data is expected after one year of treatment (in this two year trial) in 1Q07.

    MN-166 inhibits leukotriene activity, phosphodiesterases and nitric oxide synthase, all inflammatory mechanisms known to be involved in MS. Recently, MN-166 was found to have beneficial effects in several pilot clinical trials conducted in MS patients in Japan. These findings led to the issuance of a new U.S. method of use patent for MN-166 in 2002.

    "MN-166 may be an effective new approach to treating MS with the added advantage of oral dosing. Rapid completion of enrollment in this relatively large trial demonstrates our commitment to advancing our clinical programs efficiently though the Phase II proof-of-concept stage and beyond," said Yuichi Iwaki, M.D., Ph.D., Executive Chairman and Acting CEO of MediciNova, Inc.

    MediciNova acquired the rights to MN-166 from Kyorin Pharmaceutical Co. Ltd. for global markets excluding Japan, China, Taiwan and South Korea. For the past 16 years, MN-166 has been marketed in Japan and South Korea as Ketas® for the treatment of asthma and cerebrovascular disorders. Data from the existing clinical trial and post-marketing surveillance databases, which includes treatment of an estimated 3.2 million patients with these disorders, indicate that Ketas® is well tolerated.

    Source: MediciNova, Inc.(06/02/06)

    MediciNova Initiates a Phase II Clinical Trial With MN-166 in Multiple Sclerosis
    Novel Oral Compound Demonstrated Benefits in Earlier Clinical Studies in Patients with Relapsing-Remitting MS

    MediciNova, Inc., a specialty pharmaceutical company, today announced the enrollment of patients in a Phase II clinical study with MN-166 for the treatment of multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. MN-166 is an orally administered drug with a novel mechanism of action that includes the inhibition of phosphodiesterase IV.

    Under a licensing agreement with Kyorin Pharmaceutical Co. Ltd. of Tokyo, Japan, MediciNova obtained exclusive worldwide rights, except for Japan, China, Taiwan and South Korea, to develop and commercialize MN-166 for multiple sclerosis. For the past 16 years, MN-166 has been marketed in Japan as Ketas® (ibudilast), for the treatment of asthma and cerebrovascular disorders. Ibudilast was also launched in Korea in September 2002.

    "MN-166 may represent a significant advance in the treatment of relapsing-remitting MS," stated Richard Gammans, Ph.D., Chief Development Officer at MediciNova. "It has a proven record of safety and tolerability, and has the major advantage of oral dosing. In small, open label studies in patients with relapsing-remitting MS, MN-166 produced some rather encouraging activity. This Phase II study is being conducted in nine countries in Eastern Europe and will compare two oral doses of MN-166 to placebo in 300 patients with relapsing-remitting MS."

    The study will measure reduction in MS lesions in the brain as detected by MRI (magnetic resonance imaging), reductions in annualized relapse rates and functional status as determined by the EDSS (Expanded Disability Status Scale).

    About MediciNova

    MediciNova, Inc. is a publicly traded specialty pharmaceutical company focused on accelerating the global development and commercialization of innovative pharmaceutical products. MediciNova's pipeline, which includes several compounds in clinical testing, targets a variety of prevalent medical conditions, including premature labor, cancer, asthma, multiple sclerosis and anxiety disorders. For more information on MediciNova Inc., please click the link above

    Source: MediciNova, Inc.(02/08/05)

    Doctors to Test Stroke Drug for MS

    A medication currently available in Southeast Asia to treat asthma and vascular disorders in the brain is now undergoing clinical testing as a possible therapy for multiple sclerosis. The drug is known as Ketas® (ibudilast) in Japan and Korea. But it uses a code name, MN-166, in its current clinical scrutiny as a possible MS treatment.

    A Promising MS Drug?
    The trials—the latest is a Phase 2 study that just completed patient recruitment—are sponsored by the drug's manufacturer, San Diego-based MediciNova. "MN-166 may present a significant advance in the treatment of relapsing-remitting MS," said Richard Gammans, PhD, the company's Chief Development Officer. "It has a proven record of safety and tolerability, and has the major advantage of oral dosing."

    The drug works by inhibiting phosphodiesterase IV (PDE4), an enzyme that blocks the activity of a hormone in the body that mediates some cellular functions.1 In the case of MS, inhibiting PDE4 increases levels of this hormone, which results in decreased inflammation. Inflammation is a hallmark of multiple sclerosis. In the central nervous system where damage occurs as a result of the disease, inflammation is a common side effect.2

    A Varying Pathology
    Relapsing MS is the most common form of the disease, affecting an estimated 85 percent of patients. It's characterized by clearly defined relapses, or symptom flare-ups, followed by partial or complete recovery periods. The three other forms of MS include the following:

    • Primary-Progressive-Characterized by a slow and continuous worsening of disease from the moment it strikes.
    • Secondary-Progressive-Characterized by an initial phase in which relapses occur followed by recovery. But the disease then becomes steadily worse over time with or without occasional flare-ups, minor remissions, or plateaus.
    • Progressive-Relapsing-Characterized by a steadily worsening form of the disease from its onset, but which coincides with acute relapses with or without recovery. The difference between this form of MS and the relapsing form is that the periods between relapses are characterized by continuous disease progression.3

    Promising Findings So Far
    According to MedicaNova, MN-166 showed "encouraging" results in small, open label, studies with patients who were diagnosed with relapsing-remitting MS. "This Phase 2 study is being conducted in nine countries in Eastern Europe, and will compare two oral doses of MN-166 to placebo in 300 patients with relapsing-remitting MS," said Gammans.

    In the study, investigators will measure the frequency of MS lesion reduction, by taking MRI measurements of each patient. MRI (magnetic resonance imaging) is a diagnostic test used to assess the number and size of lesions in the central nervous system as a measure of MS activity.

    Yearly relapses, as well as functional ability will also be tested in the study, according to MediciNova.

    Other Uses for the Medication
    In Japan, Ketas is prescribed as a therapy for people who've experienced a stroke, or who have been diagnosed with bronchial asthma. The drug works in these cases by inhibiting blood clotting, improving blood flow in the brain, and easing allergic reactions. Experts say in these cases, the drug may release nitric oxide, a blood vessel dilator, or prostacyclin, a powerful inhibitor of blood clotting.4

    MediciNova reached a licensing agreement with Kyorin Pharmaceuticals in Tokyo to market MN-166 worldwide—except in Japan, China, Taiwan, and South Korea—as a treatment for multiple sclerosis, pending the outcome of the upcoming Phase 2 trial, as well as future clinical trials of the drug.

    MediciNova has not stated when it expects the Phase 2 trial to conclude.

    1. Dyke HJ, Montana JG. Update on the therapeutic potential of PDE4 inhibitors. Expert Opin Investig Drugs 2002 Jan;11(1):1-13.
    2. Lassman H. Recent neuropathological findings in MS—implications for diagnosis and therapy. J Neurol 2004 Sep;251 Suppl 4:IV2-5.
    3. National Multiple Sclerosis Society. What is Multiple Sclerosis? Available at: http://www.nationalmssociety.org/What%20is%20MS.asp. Accessed September 2, 2005.
    4. Kishi Y, Ohta S, Kasuya N, Sakita S, Ashikaga T, Isobe M. Ibudilast: a non-selective PDE inhibitor with multiple actions on blood cells and the vascular wall. Cardiovasc Drug Rev 2001 Fall;19(3):215-25
    .

    Source: MS Neighborhood Copyright © 2005 CuraScript, Inc. All Rights Reserved (02/09/05)

    © Multiple Sclerosis Resource Centre

    Related Items
    Ampyra (Fampyra)
    ATX-MS-1467
    Aubagio® (Teriflunomide)
    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
    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)
    Trimesta (Oral Estriol)
    Tysabri®
    Zenapax (daclizumab)


    Did you find this information useful? Would you like to comment on this page? Let us know what you think! We welcome all comments and feedback on any aspect of our website - please click here to contact us.