MedDay Reports Full Data from Pivotal Phase IIb/III MS-SPI / MS-ON Studies with MD1003 in Multiple Sclerosis at AAN
MedDay, a biotechnology company focused on the treatment of neurological diseases, today announces full study results from the MS-SPI and MS-ON trials, including the MS-SPI extension data, which will be presented at the 2016 American Academy of Neurology Annual Meeting today.
MS-SPI and MS-ON studies tested the efficacy of MD1003, a patented pharmaceutical-grade biotin administered at a dose of 300 mg per day in the treatment of multiple sclerosis (MS) and particularly of the most difficult to treat “not-active progressive MS,” for which there is no approved drug.
Overall these data show the best effect size ever observed to date and confirm the good safety profile of MD1003.
Commenting on the full study results, Prof. Ayman Tourbah, Principal Investigator of the studies, CHU de Reims, Department of Neurology, France, said: “Full results of the MS-SPI study are especially remarkable. This is the first time that a drug has reversed the progression of the disease in a statistically significant proportion of patients. In addition, if we look at the mean Expanded Disability Scale (EDSS) change, the data compare very favourably with all previous trials that looked at the same endpoint. Almost no progression was observed in patients treated with MD1003 for 24 months and this has never been observed before. When we compare these results to other trials in progressive MS that involved more than 6000 patients overall, this is clearly the best effect size ever observed. The MS-ON trial failed to reach its primary endpoint but this is most likely due to a majority of patients with relapsing remitting MS in this trial. Indeed if we focus on patients with the progressive chronic neuropathy phenotype, they seem to have benefited from the drug in the same way as patients in the MS-SPI trial. Results from both studies are therefore consistent and point to the fact that targeting neuron and oligodendrocyte metabolism represents a promising and novel disease modifying therapy approach in progressive MS, particularly in patients with a not-active progressive disease.”
MS-SPI study results
The MS-SPI study was designed to assess the potential of MD1003 to reverse disease progression in patients with not-active progressive MS. Patients included in the study had to demonstrate disease progression of disability in the previous two years with no evidence of inflammatory activity. Patients were randomized to receive either MD1003 (n=103) or placebo (n=51) for 12 months, followed by a 12-month extension phase during which all patients received MD1003 but remained blinded as to whether they had received the active drug during the first phase. The primary endpoint was particularly challenging, and defined as the proportion of patients with either improvement of EDSS or TW25 (timed 25-foot walk) after nine months (M9) confirmed at 12 months (M12), which equates to a confirmed reversion of progression.
The primary endpoint was met (p=0.0051) with 12.6% of patients in the MD1003 arm showing a confirmed reversion of progression at M9 (confirmed at M12), compared to none (0%) in the placebo arm. During the 12-month extension phase, patients initially on MD1003 exhibited sustained improvement compared to baseline, with 13.2% of patients showing improvement at M18 (confirmed at M24) and 15.4% of patients showing improvement at M24. When patients in the placebo group were switched to MD1003 for the extension phase, the proportion of responders reached 7.1% at M18 (confirmed at M24) and 11.9% at M24, demonstrating that treatment with MD1003 reversed progression in some patients switched to MD1003.
The primary judgement criterion was supported by the mean change of EDSS from baseline in the overall population. The mean EDSS decreased between M0 and M12 in the MD1003 group (-0.03) compared to progression in the placebo group (+0.13, p=0.014). During the extension phase, the values remained relatively constant compared to baseline in patients maintained on MD1003 (from -0.03 to 0.04 at M24), indicating sustained efficacy, whereas patients initially on placebo stopped progressing on EDSS once switched to MD1003 (from +0.13 at M12 to +0.15 at M24, compared to baseline).
The efficacy demonstrated on EDSS was also supported by the mean clinical global impression of change scale (CGI) which was worse at M12 in the placebo group compared to the MD1003 group (p<0.0001). It remained constant in the extension phase for patients initially on MD1003 and improved after patients were switched from placebo to MD1003. As a result no difference was observed between the two groups at the end of the extension phase (p=0.92).
MS-ON study results
The MS-ON study was designed to investigate whether MD1003 could accelerate recovery following incomplete remission of an acute relapse and/or specifically improve patients with progressive disability. For this purpose, the study enrolled patients with fixed visual loss (≥6 months) following an acute optic neuritis in the previous three years (non-progressive chronic optic neuropathy, n=62) together with MS patients showing progressive visual loss assessed at two different visits in the previous three years (progressive optic neuropathy, n=31). The placebo-controlled phase was 24 weeks (65 patients received MD1003 and 28 received a placebo) followed by a 24-week extension phase during which all patients (n=92) received MD1003. The primary endpoint was the mean change from baseline in 100% contrast visual acuity (VA) at 24 weeks of the selected eye (defined as the eye with the worst visual acuity and acute or progressive worsening within the three years prior to inclusion).
Final results showed that, overall, patients who received MD1003 improved slightly more than patients who received the placebo (average of 3.1 letters in the MD1003 arm versus 1.8 letters in the placebo arm). However the difference did not reach statistical significance. Patients in both the MD1003 and placebo groups continued to improve during the extension phase (mean of 4.25 letters in the initial MD1003 arm versus 4.0 letters in the placebo arm switched to MD1003).
Prospectively defined subgroup analyses identified that only patients with progressive ON may benefit from MD1003, while no effect was observed in the largest subgroup of patients with non-progressive ON following a relapse. During the placebo-controlled phase, patients in the progressive chronic ON subgroup who received MD1003 improved by a mean of 2.75 letters, while patients who received the placebo worsened by a mean of -1.45 letters. During the 24-week extension phase, patients who were given MD1003 continued to improve (to a mean of 4.55 letters) while those who were initially on placebo stopped worsening after they were switched to the active drug (mean of -1.2 letters at 48 weeks).
Findings from both MS-SPI and MS-ON trials show that, overall, MD1003 is well tolerated. The incidence of adverse events was similar across the two groups in both studies. In some patients, abnormal laboratory data indicated that MD1003 could affect the results of immunoassays which use biotinylated antibodies and substrates.
Commenting on the full study results, Prof. Bruce Cree, UCSF, USA, principal investigator in the upcoming US study with MD1003, commented: “ Taken together, these studies are very promising and provide hope for a condition that has thus far been largely intractable using treatments targeting neuro-inflammation. That the extension study from the SPI trial showed an apparent durability of effect suggests that high dose biotin may have disease modifying properties in addition to its proposed role in enhancing energy metabolism. Furthermore, the positive impact of high dose biotin points to a new line of inquiry in understanding the pathophysiology of progressive MS.”
About progressive MS
MS is the most common disabling neurological disease among young adults, with first symptoms typically manifesting between 20 and 40 years of age. In the majority (85%) of cases, patients experience an initial phase of relapsing-remitting neurological dysfunction (RRMS), which typically evolves into a secondary progressive disease at a later point in the clinical course (SPMS). Once MS is in the progressive phase, individuals experience a gradual worsening of neurological disability. Primary progressive MS (PPMS) characterized by disease progression from onset affects 10–15% of MS patients. Progressive disease (either SPMS or PPMS) can be further divided into active or not-active progressive disease based on the existence or not of superimposed inflammatory activity. Immunosuppressive and immunomodulatory drugs have been shown to decrease the frequency of relapses and CNS lesions in relapsing remitting MS. These drugs may also delay progression in the subgroup of patients with active progressive MS. However, there is currently no drug targeting non-active progressive MS, which represents the larger and most difficult to treat population.
In relapsing MS, lymphocytes and monocytes of the peripheral adaptive immune system infiltrate perivascular brain and spinal cord tissue causing focal inflammation that can be identified on imaging as acute contrast enhancing lesions. The histopathological hallmark of these lesions is injury to oligodendroglia cells that wrap axons in myelin, the cell membrane that enhances electrical resistance and allows saltatory conduction through the nervous system. Axons themselves are typically relatively spared. In contrast, progressive MS is mainly associated with progressive axonal degeneration, chronic demyelination and, usually, little or no inflammation. It is considered that axonal degeneration results from energy failure caused by chronic demyelination and mitochondrial dysfunction.
MD1003 is a patented, highly dosed pharmaceutical grade biotin that has already shown efficacy in patients with progressive multiple sclerosis. MD1003 has a unique mode of action which potentially acts on two targets related to progressive MS: (1) it activates the Krebs cycle, the main route for energy production that protects against axonal degeneration and (2) it potentially activates acetyl-CoA carboxylases (ACC1 and ACC2), the rate-limiting enzymes in the synthesis of fatty acids required for myelin repair. The drug is already commercialized in some European countries under early-access programs.
MedDay is a privately held biotechnology company developing new drugs targeting brain metabolism for neurodegenerative diseases. The company was founded in 2011 by Frédéric Sedel, MD, PhD (Chief Executive Officer); and Guillaume Brion, MD (Chief Operating Officer). The Company’s most advanced pipeline candidate is MD1003 for the treatment of primary and secondary progressive multiple sclerosis. For more information, please see: www.medday-pharma.com.
Sedel, et al. Mult Scler Relat Disord. 2015 Mar;4(2):159-69
Sedel, et al. Neuropharmacology. 2015 Sep 5. doi: 10.1016/j.neuropharm.2015.08.028.
Peyro Saint Paul L et al. Expert Opin Drug Metab Toxicol. 2016 Mar;12(3):327-44
Om Business Wire
Business Wire, a Berkshire Hathaway company, is the global leader in multiplatform press release distribution.
Følg saker fra Business Wire
Registrer deg med din epostadresse under for å få de nyeste sakene fra Business Wire på epost fortløpende. Du kan melde deg av når som helst.
Siste saker fra Business Wire
WilsonHCG Unveils Fourth Annual Fortune 500 Top 100 Employment Brands Report17.1.2018 14:00 | Pressemelding
WilsonHCG, global leader and premium provider of innovative talent solutions, has revealed its 2018 Fortune 500 Top 100 Employment Brands report – the company’s fourth annual objective research, evaluation and ranking of how well Fortune 500 organizations brand themselves as an “employer of choice”. New to the 2018 report, WilsonHCG also analyzed the top 25 Global Fortune 500 employment brands. Based on six key employment branding categories and tens of thousands of data points, Johnson & Johnson earned the top overall ranking for the second year in a row (third consecutive top-10 performance). Intel earned the No. 2 overall spot, with three companies – IBM, Procter & Gamble and Lockheed Martin – tying for third overall. Rounding out the top 10 are General Motors, JPMorgan Chase, Dow, Cummins, and ADP (each tied for No. 6 overall). “We’re in the midst of the most competitive hiring environment of our time, as today’s talent has full transparency into what they're worth – and what compe
Mavenir Announces Virtualized Media Breakout Controller, Bringing 5G Edge Architectures to Legacy Networks17.1.2018 14:00 | Pressemelding
Mavenir, focused on transforming mobile network economics for Communications Service Providers, today announced its virtualized Media Breakout Controller (vMBC), a single white box routing platform that enables carriers to host virtual Routing, Firewall, and User plane data offload. Today’s networks, whether 3G, 4G or 5G, are under pressure to provide increased bandwidth in support of LTE and its frequency combinations, and reduce latency for network interaction, resulting in a continual need to increase capacity for traffic transported through the core of the network. Multi-Access Edge Computing standardization (MEC) is trying to resolve some of these issues by placing compute functionality at the edge but it is still mostly controlled from the core, based on conventional centralized architectures. The ability to scale network functionality using virtual elements and COTS HW platforms allows network functionality to be deployed at any location. Mavenir’s innovative solution offers the
Greece’s Largest Lender Piraeus Bank to Fully Eliminate ELA in 201817.1.2018 13:42 | Pressemelding
Greece’s Piraeus Bank ends 2017 with NPL stock below EU20b vs EU20.1b target, according to a Bloomberg report. For 2018, the Bank projects a credit growth rate of 1% for the Greek banking sector, with the granting of new loans mainly to corporates and SMEs. This will be the first loan growth since the onset of the crisis. Loan growth is expected to come mainly from corporate and SME lending. In 2017 Piraeus, which holds a dominant position in the SMEs market (80% of the SMEs market having a banking relationship with Piraeus Bank), generated close to €2.8bn new loans, ahead of its budget, targeting to be close to €5bn by 2020. Loans to deposit ratio converging towards 100%, signaling the readiness of the Bank to satisfy stronger loan demand coming. The Bank has reduced its ELA reliance significantly to €5.5bn level at the end of 2017 from €12bn at the beginning of the year, currently below €4.5bn. “We have delivered a significant reduction in euro-system funding. This is strongly in lin
SailPoint Closes out an Award-Winning Year in 201717.1.2018 13:00 | Pressemelding
SailPoint Technologies Holdings, Inc. (NYSE: SAIL), the leader in enterprise identity management, closed out an award-winning year in 2017, receiving industry recognition spanning technology innovation, business performance and company culture. “Last year was a phenomenal one for SailPoint on many fronts. Our goal as a company has always been to focus on delivering innovative solutions to address our customers’ identity needs, so to see that innovation highlighted by industry analysts is great validation for us,” said Mark McClain, CEO and Co-founder of SailPoint. “Likewise, our people are invaluable to us as they truly drive our company’s innovation and exemplify our core values daily, so to have them provide such positive feedback is an incredible recognition for all of us as team.” Key award wins and industry accolades achieved to close out 2017 include: SailPoint was named one of the fastest growing technology companies on Deloitte’s 2017 Technology Fast 500™ for the fifth consecut
YuppTV White Labelled OTT Platform Equips Aastha Group’s TV Channels Foray in Digital World17.1.2018 12:30 | Pressemelding
Global leader for South-Asian content, YuppTV powers Aastha Group’s TV Channels (Aastha, Aastha Bhajan, Vedic & Arihant) voyage into the world of OTT. Aastha, the pioneer spiritual and cultural brand will be utilising YuppTV’s white-labelled video platform to be present across the digital world of web, mobile, and connected TVs. Aastha mobile app was launched today by Param Pujya Swami Ramdev Ji Maharaj and Shraddhey Shree Acharya Bal Krishan Ji. On this occasion, Swami Ji stated that it's the beginning of a new era in the journey of Aastha the leading Indian Channel on spirituality and natural wellness through Yoga and Ayurveda. “Aastha” App would bring people across the world closer to Indian spirituality and meditation. Now, one can watch their favourite programs of previous nine days on “Aastha” Mobile App. anytime anywhere, as per their convenience. Extending the words of Swami Ramdev Ji, Shraddhey Balkrishan Ji said that the “Aastha” Mobile app would play a huge role in connectin
Nasdaq Will Use Rimini Street for Support of Some of Its Internal Corporate Systems17.1.2018 12:00 | Pressemelding
Rimini Street, Inc. (Nasdaq: RMNI), a global provider of enterprise software products and services, and the leading third-party support provider for Oracle and SAP software products, today announced that Nasdaq will use Rimini Street for support of its human resource management system. This press release features multimedia. View the full release here: http://www.businesswire.com/news/home/20180117005048/en/ Nasdaq will use Rimini Street for Support of Some of its Internal Corporate Systems (Photo: Business Wire) As with all Rimini Street clients, Nasdaq has an assigned dedicated Primary Support Engineer (PSE) as its main point of contact for all support cases. Rimini Street PSE’s have an average of 15 years’ experience in their respective applications, and all clients receive industry-leading 24x7x365 service level commitments. “We are pleased to welcome Nasdaq to the fast-growing Rimini Street family of clients,” said Seth A. Ravin, Rimini Street CEO. “We have been disrupting the ent
I vårt presserom finner du alle våre siste saker, kontaktpersoner, bilder, dokumenter og annen relevant informasjon om oss.Besøk vårt presserom