Business Wire

MedDay Reports Full Data from Pivotal Phase IIb/III MS-SPI / MS-ON Studies with MD1003 in Multiple Sclerosis at AAN

Del

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).

Safety

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.”

Ends

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.

About MD1003

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.

About MedDay

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.

References

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

Contact information

MedDay Pharmaceuticals
contact@medday-pharma.com
or
Consilium Strategic Communications
Mary-Jane Elliott, Jonathan Birt, Laura Thornton
+44 (0)20 3709 5700
medday@consilium-comms.com

Om Business Wire

Business Wire
Business Wire
24 Martin Lane
EC4R 0DR London

+44 20 7626 1982http://www.businesswire.co.uk

(c) 2018 Business Wire, Inc., All rights reserved.

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

AURAK Enters into a Memorandum of Understanding with Al-Farabi Kazakh National University22.7.2018 09:52Pressemelding

The American University of Ras Al Khaimah (AURAK) President, Professor Hassan Hamdan Al Alkim, and the Al-Farabi Kazakh National University (KazNU) Rector, Professor Galimkair Mutanov, of the Republic of Kazakhstan, signed a Memorandum of Understanding (MoU), agreeing to exchange students, faculty, and research. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20180722005025/en/ The Al-Farabi Kazakh National University (KazNU) Rector, Professor Galimkair Mutanov, of the Republic of Kazakhstan and the American University of Ras Al Khaimah (AURAK) President, Professor Hassan Hamdan Al Alkim, exchange a gift to commemorate their universities uniting in an MoU agreement. (Photo: AETOSWire) In the spirit of fostering a close international relationship between the Republic of Kazakhstan and the United Arab Emirates, developing bilateral relations in educational and scientific fields, and wishing to make their own contributions to the

Philip Morris International Announces Non-Executive Board Chairman Louis Camilleri to Assume CEO Role at Ferrari S.p.A.21.7.2018 18:19Pressemelding

The board of directors of Philip Morris International (NYSE:PM) has its board member, Sergio Marchionne, and his family in our thoughts and prayers during this challenging time. We congratulate our board chairman, Louis Camilleri, as he assumes the role of CEO of Ferrari S.p.A. The long term relationship between our two companies is deep and meaningful and we look forward to continued business collaboration. Mr. Camilleri will continue to serve as non-executive chairman of the PMI board. Philip Morris International: Who We Are We are a leading international tobacco company engaged in the manufacture and sale of cigarettes and other nicotine-containing products in markets outside the United States of America. We’re building our future on smoke-free products. Through multidisciplinary capabilities in product development, state-of-the-art facilities and scientific substantiation, we aim to ensure that our smoke-free products meet adult consumer preferences and rigorous regulatory requirem

Loxam Announces a Conditional Agreement to Acquire UK Platforms20.7.2018 14:51Pressemelding

Loxam Group (“Loxam”) announces that its wholly-owned subsidiary Nationwide Platforms Limited (“Nationwide”) has entered into a conditional agreement with HSS Hire Group plc (“HSS”) with respect to the acquisition of UK Platforms Limited (“UKP”). UKP specializes in renting powered access equipment from its 12 branches located throughout the United Kingdom. The company has approximately 130 employees and operates a fleet of 3,000 units. UKP is controlled by HSS since 2013. As part of this transaction, Nationwide has entered into a commercial agreement with HSS to provide powered access equipment to complement HSS’ existing fleet. The closing of the transaction is subject to the approval by HSS’ shareholders and the confirmation that it will not be referred to the Competition and Mergers Authority. The transaction is expected to close before year end 2018. Don Kenny, CEO of Loxam’s Powered Access Division states: “I am delighted with the acquisition of UKP which will further reinforce NW

Schlumberger Announces Second-Quarter 2018 Results20.7.2018 11:00Pressemelding

Schlumberger Limited (NYSE: SLB) today reported results for the second quarter of 2018. (Stated in millions, except per share amounts) Three Months Ended Change Jun. 30, 2018 Mar. 31, 2018 Jun. 30, 2017 Sequential Year-on-year Revenue $8,303 $7,829 $7,462 6% 11% Pretax operating income $1,094 $974 $950 12% 15% Pretax operating margin 13.2% 12.4% 12.7% 75 bps 45 bps Net income - GAAP basis $430 $525 $(74) -18% n/m Net income, excluding charges & credits* $594 $525 $488 13% 22% Diluted EPS - GAAP basis $0.31 $0.38 $(0.05) -18% n/m Diluted EPS, excluding charges & credits* $0.43 $0.38 $0.35 13% 23% *These are non-GAAP financial measures. See section below entitled "Charges & Credits" for details. n/m = not meaningful Schlumberger Chairman and CEO Paal Kibsgaard commented, “The second quarter was both busy and exciting for Schlumberger as we completed a number of major milestones in preparation for the broad-based global activity upturn that is now emerging. We delivered solid top-line gro

H.I.G. Capital Announces the Sale of KidsFoundation19.7.2018 19:50Pressemelding

H.I.G. Capital (“H.I.G.”), a leading global private equity investment firm with more than €21 billion of equity capital under management, announced today that one of its affiliates has entered a definitive agreement to sell the KidsFoundation Group (“KidsFoundation”), the Dutch market leader in childcare services, to Onex Corporation (“Onex”)(TSX:ONEX). Terms were not disclosed. Headquartered in Almere, the Netherlands, KidsFoundation provides high-quality childcare to nearly 30,000 children between the ages of six weeks and 12 years. H.I.G. created KidsFoundation in 2014 through the acquisition of assets from the estate of Estro Group. During H.I.G.’s ownership, the company has developed strongly with significant capital invested by H.I.G. to create a high-quality childcare offering. H.I.G. worked with KidsFoundation management to optimise the footprint of the company by exiting loss-making locations, introduce new IT systems to drive operational improvement and develop an internal M&

SIG Combibloc Group Holdings S.à r.l.: 2018 Second Quarter Results19.7.2018 16:01Pressemelding

We are pleased to announce our quarterly conference call to discuss the results of SIG Combibloc Group Holdings S.à r.l. for the second quarter ended June 30, 2018. Date: Monday, July 23, 2018 Time: 15.00 CEST / 14.00 BST / 9.00 EDT The call information will be distributed on our secure site. If you would like access to our call, please contact investor.relations@sig.biz . Regards, SIG Combibloc Group Holdings S.à r.l. View source version on businesswire.com: https://www.businesswire.com/news/home/20180719005634/en/ Contact information SIG Combibloc Group Holdings S.à r.l. Jennifer Gough investor.relations@sig.biz