ECTRIMS (European Committee for Treatment and Research in Multiple Sclerosis), concluded their 2015 annual meeting with ‘late breaking news’ sessions, which included the results from two separate drugs being looked at for treatment in primary progressive MS (PPMS). This is significant, because as most of you know, PPMS has no official, authorized disease modifying therapy, although several drugs are used off-label.
One drug for PPMS has gotten most of the attention- that would be Ocrelizumab. The other one in the shadows is Biotin. I offer here the abstracts for both of these drugs so you might learn a bit more about them and the trial outcomes, although there are still many details outstanding. Note at the end of each, they give more information about the researchers on the project and their affiliations. Yes, there are many of us who do like reading these, even if all the information doesn’t make complete sense.
BIOTIN/ MEDDAY PHARMACEUTICALS
Type: Oral LB
Abstract Category: Invited / Oral LB / Poster LB
Introduction: High doses of Biotin, a co-enzyme for acetylCoA carboxylase, a potentially key-enzyme in myelin synthesis, was evaluated over placebo in patients with progressive multiple sclerosis (MS).
Methods: MS-SPI is a randomized, double-blind, placebo-controlled (2:1) trial of oral biotin 300 mg / day in patients with secondary (SPMS) or primary (PPMS) progressive MS. Treatment duration was 48 weeks. The primary endpoint was the proportion of patients who improved at M9 and confirmed at M12, defined as decreased EDSS or improved TW25 of at least 20%. Main secondary endpoints included mean EDSS change, clinical impression of change (CGI and SGI).
Results: 13/103 (12·6%) of MD1003-treated patients achieved the primary endpoint versus none of 51 placebo-treated patients (p=0·0051). The primary endpoint was confirmed by a significant decrease in the mean change EDSS, CGI and SGI in the MD1003 group. The proportion of responders was higher in patients (1) with a baseline EDSS score in the [4.5;5] range compared to patients with a baseline EDSS score in the [6;7], (21.4% versus 9.3%); (2) with no concomitant fampridine administration compared to patients with concomitant fampridine administration (20.7% versus 2.2%) and (3) with SPMS, compared to PPMS (14.8% versus 9.5%). Treatment with MD1003 significantly reduced mean EDSS scores, CGI and SGI in the sub-group of patients with SPMS, and in patients with or without concomitant fampridine administration. Although similar trends were observed in the PPMS subgroup, results were not statistically significant.
Conclusion: Biotin significantly improved MS-related disability and decreased the risk of progression in patients with progressive MS. The effect was more pronounced in patients with SPMS although the relative low number of patients with PPMS in the study precludes robust conclusions. Patients with concomitant treatment with fampridine benefited from biotin in terms of decreased risk of progression and clinical global impression.
Sponsored by Medday Pharmaceuticals
AT is the principal investigator and discloses travel grants from MedDay
FS is CEO and a shareholder at MedDay Pharmaceuticals (the study sponsor)
CL-F ,GE, MC, CP, SV, JD, MD, PC, OG, GD, D-AL, TM, PL, BB JP have nothing to disclose in relation with this abstract
Type: Oral LB
Abstract Category: Invited / Oral LB / Poster LB
Background: Primary progressive multiple sclerosis (PPMS) accounts for 10-15% of the MS population. There is currently no approved disease-modifying treatment for PPMS. B cells are believed to contribute to the pathogenesis of MS, including PPMS. Ocrelizumab (OCR) is a recombinant humanised monoclonal antibody that selectively targets CD20+ B cells.
Objectives: ORATORIO is a Phase III, multicentre, randomised, double-blind, placebo-controlled study aiming to assess the efficacy and safety of OCR in patients with PPMS (NCT01194570).
Methods: Patients were randomised (2:1) to receive OCR 600 mg (given as two 300 mg intravenous infusions 14 days apart) or matching placebo every 24 weeks for at least 120 weeks or until approximately 253 three-month confirmed disability progression events occurred. Eligibility criteria included an age of 18-55 years, a diagnosis of PPMS (2005 revised McDonald criteria); Expanded Disability Status Scale (EDSS) score of 3.0-6.5 at screening; disease duration (since MS symptoms) of < 15 years in patients with an EDSS score of > 5.0 at screening and < 10 years in patients with an EDSS score of ≤ 5.0 at screening; and documented evidence of elevated immunoglobulin index and/or presence of oligoclonal bands within the CSF. The primary endpoint is time to onset of confirmed disability progression, defined as a ≥ 12-week sustained increase in EDSS score.
Results: Overall, 732 patients were randomised at 183 sites. Mean age at baseline was 44.6 years; 49.3% of patients were female and 94.1% were white. Mean (standard deviation, SD) baseline EDSS score was 4.70 (1.17); mean (SD) duration since MS symptom onset was 6.48 (3.89) years; and mean (SD) duration since PPMS diagnosis was 2.82 (3.22) years. The number of patients untreated with any MS medication in the prior 2 years was 656 (89.6%). At baseline, 26.4% of patients had gadolinium-enhancing (Gd+) T1 lesions; mean (SD) number of Gd+ T1 lesions was 1.0 (4.31); median (min-max) volume of T2 lesions was 6.96 (0-90.3) cm3; and mean (SD) normalised brain volume was 1464.99 (85.96) cm3 on brain magnetic resonance imaging.
Conclusions: The ORATORIO baseline characteristics are consistent with disease characteristics of a PPMS population. As the primary endpoint is an event-driven analysis, the treatment period will be extended until approximately 253 three-month confirmed disability progression events have occurred. The results from this study will be presented after this target is reached.
Research funded by F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Xavier Montalban has received speaking honoraria and travel expenses for scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Bayer Schering Pharma, Biogen Idec, Merck Serono, Genentech Inc., Genzyme, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, GSK, F. Hoffmann-La Roche Ltd., Almirall, NMSS and MSIF; he is also Editor for Clinical Cases for MSJ.
Bernhard Hemmer has served on scientific advisory boards for F. Hoffmann-La Roche Ltd., Novartis, Bayer Schering, Merck Serono, Biogen Idec, GSK, Chugai Pharmaceuticals, Micromet, Genentech Inc. and Genzyme Corporation; serves on the international advisory board of Archives of Neurology and Experimental Neurology; has received speaker honoraria from Bayer Schering, Novartis, Biogen Idec, Merck Serono, F. Hoffmann-La Roche Ltd. and Teva Pharmaceutical Industries Ltd.; has received research support from Biogen Idec, Bayer Schering, Merck Serono, Five Prime Therapeutics Inc., Metanomics, Chugai Pharmaceuticals and Novartis; and has filed a patent for the detection of antibodies and T cells against KIR4.1 in a subpopulation of MS patients and genetic determinants of neutralising antibodies to interferon-beta.
Kottil Rammohan has received honoraria for participating in advisory boards and consulting for Acorda, Biogen Idec, EMD Serono, Genentech/F. Hoffmann-La Roche Ltd., Genzyme and Teva; he has also received grants from Accera, NIH and NMSS.
Gavin Giovannoni has received honoraria from Abbvie, Bayer HealthCare, Biogen, Canbex, FivePrime, Genzyme, GlaxoSmithKline, GW Pharma, Merck Serono, Novartis, Protein Discovery Laboratories, Roche, Synthon, Teva Neuroscience, UCB, and Vertex; research grant support from Biogen, Ironwood, Merck Serono, Merz, and Novartis; and compensation from Elsevier as co−Chief Editor of MS and Related Disorders.
Jerome de Seze has nothing to declare.
Amit Bar-Or has received personal compensation for consulting, serving on scientific advisory boards and/or speaking activities from Bayer, Bayhill Therapeutics, Berlex, Biogen Idec, BioMS, Diogenix, Eli Lilly, Genentech Inc., GSK, Guthy-Jackson/GGF, Merck Serono, Novartis, Ono Pharmacia, F. Hoffmann-La Roche Ltd., Sanofi-Aventis, Teva Neuroscience and Wyeth.
Douglas Arnold reports equity interest in NeuroRx Research, which performed the MRI analysis for the trial, and consultation fees from Acorda, Biogen Idec, Genzyme, F. Hoffmann-La Roche Ltd., Innate Immunotherapeutics, MedImmune, Mitsubishi Pharma, Novartis, Receptos, Sanofi-Aventis and Teva.
Annette Sauter is an employee and/or shareholder of F. Hoffmann-La Roche Ltd.
Algirdas Kakarieka is an employee and/or shareholder of F. Hoffmann-La Roche Ltd.
Donna Masterman is an employee of Genentech Inc., a member of the Roche Group.
Peter Chin is an employee of Genentech Inc., a member of the Roche Group.
Hideki Garren is an employee and/or shareholder of F. Hoffmann-La Roche Ltd.
Jerry Wolinsky has received compensation for service on steering committees or data monitoring boards for Novartis, F. Hoffmann-La Roche Ltd., Genzyme and Teva Pharmaceuticals; consultant fees from AbbVie, Actelion, Alkermes, Athersys Inc., EMD Serono, Forward Pharma, Genentech Inc., Genzyme (Sanofi), Novartis, F. Hoffmann-La Roche Ltd., Teva and XenoPort; and research support from Genzyme, Sanofi, the NIH and the NMSS through the University of Texas Health Science Center at Houston (UTHSCH) and royalties for monoclonal antibodies out-licensed to Chemicon International through UTHSCH.