MN-166 Data

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MN-166 Data

Postby Cyclops » Wed Oct 29, 2008 3:17 pm

I found this on the ECTRIMS website. Not sure if it has already been posted:

Cyclops

Clinical effect of the neuroprotectant MN-166 in relapsing multiple sclerosis: year 2 data
R. Gammans1; F. Barkhof2; J. Drulovic3
1. Development, MediciNova, San Diego, CA, USA.
2. VUMC, Amsterdam, Netherlands.
3. Institue of Neurology, Belgrade, Serbia.



MN-166 (ibudilast) is an orally administered small molecule with neuroprotectant and anti-inflammatory properties. In year 1 of this 2-year study (Drulovic et al., ECTRIMS 2008), MN-166 at 60mg/day significantly reduced percent brain volume (PBV) loss and prolonged time-to-first relapse by 157 days (p=0.04), but did not significantly reduce cumulative new lesion count, the primary study endpoint, in relapsing–remitting multiple sclerosis (RRMS) patients. MN-166 produced a dose-related reduction in change of new inflammatory lesions to PBH (p=0.01; Gammans et al., ENS 2008).

To evaluate the clinical effects and safety of MN-166 in RMS patients over 2 years.

RRMS (93%) or SPMS with relapses (7%) patients and ≧ 1 T1 Gd-lesion were randomized to placebo (PBO, n=100) or MN-166 at 30 (n=94) or 60mg/day (n=98); for year 2 PBO patients were pre-assigned to MN-166 at 30 (n=49) or 60mg/day (n=51). Clinical and magnetic resonance imaging (MRI) evaluations were every 2 months for 2 years.

Two hundred and sixty four (96% of PBO - 30mg/day, 97% of PBO - 60mg/day, 82% of 30mg/day and 87% of 60mg/day) patients entered year 2. Significantly fewer patients treated with MN-166 for 2 years at 30 or 60mg/day than patients treated with PBO followed by MN-166 at either dose for 1 year had a sustained disability progression (+1 point on Extended Disability Status Scale – EDSS – for >=4 months) (2 year MN-166 10.4%, PBO to MN-166 21%, p=0.03). MN-166 at 60mg/day for 2 years significantly (p=0.04) attenuated loss in PBV compared with the remaining groups. MN-166 was well tolerated at either dose. Three of 85 MN-166 60mg/day patients discontinued in year 2 for adverse effects compared with none in the other groups. Only GI events were more frequent in year 2 on MN-166 at 60mg/day (11%) and 30mg/day (4.2%) PBO-to-60mg/day (2%) PBO-to-30mg/day (0%). Depression was reported in 5% of the 60mg/day and 3% of the PBO-to-60mg/day patients towards the end of the second year of the study.

The findings in this 2-year study on three independent measures – reduced disability progression (50%), reduced conversion of inflammatory lesions to PBH (37%) and reduced PBV loss – suggest that MN-166’s clinical benefit results predominantly from protecting neurons from damage. These data suggest that MN-166 reduces progression of MS.
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Postby dignan » Sat Mar 06, 2010 10:42 am

This is pretty much the same as what Cyclops posted in 2008, but it took this long to finally publish the results in a journal. I still think this is promising -- it provides neuroprotection and reduces disability progression...maybe...


Ibudilast in relapsing-remitting multiple sclerosis. A neuroprotectant?

Neurology. 2010 Mar 3.
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.

BACKGROUND: 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.

http://www.ncbi.nlm.nih.gov/pubmed/20200338
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Postby Frank » Sun Mar 07, 2010 7:18 am

Another coverage of ibudilast on acceleratedcure together with the (failed) results of a trial combining Inosine with INF-b.

--Frank


Two studies appearing back-to-back in PubMed today evaluated agents with potential neuroprotective activities for efficacy in MS. One of the studies came out with a positive finding, the other produced no evidence for efficacy.

The first study evaluated an oral drug called ibudilast which belongs to a class called phosphodiesterase inhibitors. This drug is used in Japan and Korea to treat asthma and cerebrovascular disorders. Based on pilot MS trial results and hints of possible neuroprotective effects in animal studies, a group of investigators decided to conduct a multi-center, placebo-controlled trial to see whether it would affect MS disease activity and progression. 297 people with MS participated and were randomized to 60 mg or 30 mg ibudilast daily, or placebo. At the end of 12 months, a 12-month extension followed, with placebo subjects moved to one of the two ibudilast doses.

The results of the study showed no major effect of the drug on indicators of disease activity such as number or volume of new lesions or relapses. However, subjects on ibudilast, particularly the higher dose, had lower brain atrophy rates. A comparison of MRIs showed that ibudilast treatment was associated with fewer lesions converting to MRI "persistent black holes," an indication of lasting damage. In addition, after 24 months, those subjects who had been on ibudilast from the beginning were less likely to have progressed on the EDSS scale than those who were initially on placebo.

No serious safety concerns were reported at the doses tested, so it seems that ibudilast is worth further study. Since the drug had little effect on inflammatory activity, the authors suggest studying it in conjunction with an immune-modulating drug to see if the combination results in both lower disease activity and improved brain tissue preservation.


The second study did assess this type of combination -- inosine plus IFN-beta -- but did not demonstrate the hypothesized effect on disability progression. Inosine is a precursor of uric acid, a protein which appears to be neuroprotective based on lab and animal studies, but is found in decreased levels in the serum of people with MS. 159 subjects were randomized to IFN-beta combined with either oral inosine supplements or placebo and followed for 24 months. Unfortunately, the primary endpoint of reduced risk of EDSS progression was not met; nor were any other endpoints having to do with disability or relapses. The authors conclude that the uric acid pathway and other neuroprotective mechanisms need to be better understood in MS. They also noted, as has been observed before, that success in treating EAE is not a great predictor of success in human trials.
Treatment: Gilenya since 01/2011, CCSVI both IJV ballooned 09/2010, Tysabri stopped after 24 Infusions and positive JCV antibody test, after LDN, ABX Wheldon Regime for 1 year.
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