MedDay, a biotechnology company that develops new drugs for nervous system disorders, announced an update on the progress of its development pipeline with its lead product MD1003 for the treatment of primary and secondary progressive multiple sclerosis (MS). The first study is expected to be complete in early 2015, while the second should be complete in late 2015.
The company aims to develop drugs for neurological and psychiatric diseases through brain metabolism and is currently developing a compound to target progressive MS, the ultra-orphan condition adrenoleukodystrophy (AMN), Alzheimer’s disease, and autism.
MedDay’s MD1003 for MS, which have been approved for patent protection in the US and Europe, is a highly concentrated formulation of D biotin (vitamin H), a key co-factor for enzymes involved in energy production and synthesis of myelin. The company announced that trials for drug use for the treatment of primary and secondary progressive multiple sclerosis, continue to progress well.
A pilot open label study that enrolled 23 patients with primary and primary and secondary progressive MS confirmed the efficacy of MD1003. The trial is expected to enroll the last patient this month, and results should be presented on 18 April 2015 during the American Academy of Neurology annual meeting. Furthermore, the company has two-phase 2b/3, placebo-controlled pivotal studies in progress at 21 MS centers in France and in the UK where 250 patients are enrolled.
MedDay’s second trial in MS patients with permanent visual loss after optic neuritis, called “MS-ON’, is expected to retrieve results during the second semester of 2015.
In a recent press release, Frédéric Sedel, Chief Executive Officer of MedDay said, “MedDay is making rapid progress in demonstrating the clinical viability of its unique approach to the development of treatments that target the nervous system’s metabolism. This approach and our expertise come from the study of rare inborn metabolic errors. We anticipate the completion of our first pivotal trial in primary and progressive MS, an area in which currently available MS treatments have little or no effect, later this month and we are on track to complete a second study this year.”
Moreover, in order to develop additional pipeline assests, the company developed a research platform called SPECMET in collaboration with Assistance Publique Hôpitaux de Paris (APHP) and the Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA). SPECMET aims to identify new treatment targets through cerebrospinal fluid metabolomics analyses.
“Our metabolomics platform, SPECMET, continues to identify specific metabolic signatures in major central nervous system disorders, providing numerous opportunities for further pipeline developments. By focusing on compounds that already have known activity in neurological metabolic pathways, we believe we can quickly demonstrate clinical proof of concept.”, Sedel said in the press release.
Source: Multiple Sclerosis News Today © BioNews-tx.com 2015 (19/01/15)
Arena Pharmaceuticals, Inc. released the first results from its phase 1b trial that for the evaluation of an oral drug candidate called APD334 for the treatment of autoimmune diseases, such as multiple sclerosis (MS). The multiple ascending dose clinical trial demonstrated encouraging findings about the drug, which is designed to target the sphingosine 1-phosphate subtype 1 (S1P1) receptor.
The scientists analyzing the drug observed a dose-dependent effect on lymphocyte count lowering in blood, with mean decreases from baseline of up to 69%, due to APD334, within the phase 1b, as announced by the company in a press release. On average, lymphocyte was registered as recovered to baseline a week after the conclusion of dosing.
“Lymphocyte lowering at the level demonstrated in this trial has been shown to correlate with clinical efficacy in Phase 2 and Phase 3 trials of other S1P1 modulators in multiple sclerosis, psoriasis and ulcerative colitis,” explained the Senior Vice President and Chief Medical Officer of Arena, William R. Shanahan, M.D. “The results of this trial support investigation of the efficacy and safety of APD334 in patients with autoimmune diseases.
In addition, no significant safety findings worth noting regarding heart rate or rhythm, pulmonary function, or elevations in liver enzymes were registered. The adverse events related to the treatment most commonly noted were mild or moderate contact dermatitis, headache, constipation and diarrhea, despite the fact that none of them were clearly attributed to the drug, and there were no discontinuations for adverse events nor serious adverse events observed.
The purpose of the randomized, double-blind, placebo-controlled phase 1b clinical trial was to assess the safety, tolerability, pharmacodynamics and pharmacokinetics of multiple-ascending doses of APD334. The study was conducted in five different dosing cohorts, which comprised a total of 50 healthy participants, who were administrated with APD334, as well as 10 other who received placebo during a 21-day period.
“Based on these impressive results, we plan to expedite APD334 into Phase 2 clinical trials for ulcerative colitis and Crohn’s disease,” stated Jack Lief, Arena’s President and Chief Executive Officer. “The advancement of this promising drug candidate further demonstrates Arena’s focused expertise in discovering and developing innovative drug candidates targeting G protein-coupled receptors that have the potential to improve health,” he added.
Source: Multiple Sclerosis News Today © BioNews-tx.com 2015 (16/01/15)
MedDay has provided an update on the progress of its lead product MD1003 for the treatment of primary and secondary progressive multiple sclerosis (MS), which is expected to complete its first pivotal study in Q1 2015. A second pivotal study is on track for completion by the end of 2015.
Development of MedDay’s lead candidate, MD1003, for the treatment of primary and secondary progressive multiple sclerosis, continues to progress well. Progressive MS is an area of significant unmet need. MD1003 is a highly concentrated formulation of D biotin (vitamin H). Patents protecting the dose and use in multiple sclerosis (MS) as an active pharmaceutical ingredient have been approved in the US and Europe, offering protection until 2032. Biotin is a key co-factor for enzymes involved in energy production and synthesis of myelin.
Proof of concept has been obtained in a pilot open label study involving 23 subjects with primary and secondary progressive MS. Two phase 2b/3, placebo-controlled, pivotal studies are ongoing, involving 250 patients and 21 MS reference centers in France and the UK. The placebo-controlled phase of the first registration trial MS-SPI is almost complete. The last patient visit is expected in mid-January 2015 and we aim to present the results at the American Academy of Neurology annual meeting on 18 April 2015.
Results of the second registration trial in MS, “MS-ON”, dedicated to patients with permanent visual loss following optic neuritis, are expected in H2 2015.
Source: MedDay (14/01/15)
Biogen Idec Inc’s experimental drug for multiple sclerosis showed signs that it could help repair nerve damage in patients’ eyes, a tentatively positive step for a drug aimed at reversing progression of the disease.
In a mid-stage trial of 82 patients, Biogen’s drug showed a 34 percent improvement in those who completed the study. The result fell a hair below the threshold for statistical significance. Including patients who didn’t complete the study, results were positive but didn’t reach statistical significance, Biogen said today in a statement.
Biogen climbed 2.2 percent to $361 in early trading. The company, based in Cambridge, Massachusetts, gets most of its revenue from multiple sclerosis drugs like Tecfidera and is pushing for new treatments for the disease, which affects 2.3 million people worldwide. There are no approved cures for multiple sclerosis, only drugs that help suppress the immune system or manage symptoms.
“This is a huge hope,” said Tim Coetzee, chief research officer at the National Multiple Sclerosis Society, in a telephone interview before Biogen’s news was released. “Rebuilding the nervous system is the next frontier of how we tackle treating MS, and for many people who live with MS, strategies like this are a source of hope that they could get some function back.”
Multiple sclerosis causes the immune system to attack myelin, a fatty substance that coats and protects nerve fibres. Patients can experience tingling, problems with walking and degrading vision. Their symptoms get worse as MS progresses.
Biogen’s drug, called BIIB033, targets a protein in the the central nervous system that regulates myelin production. The antibody could spur the myelin to regrow and reverse the progression of the disease.
Biogen’s mid-stage trial tested the drug’s effects on optic neuritis, inflammation of the optic nerve often caused by multiple sclerosis. Interpreting the data may not be clear cut, according to Eric Schmidt, an analyst at Cowen & Co.
“Optic neuritis is really just a ‘proof of biology’ indication for MS,” he said in an e-mail before Biogen’s announcement today. “We really don’t know how data from one indication will translate to the other.” More studies that directly measure its effects on multiple sclerosis are needed before any conclusions can be drawn, Schmidt said.
While patients in the trial generally tolerated the drug well, two patients had hypersensitivity reactions around the time the drug was infused, and one had an elevation in enzymes that can cause liver damage, which resolved itself when the patient stopped using the medicine.
Source: Bloomberg ©2015 Bloomberg L.P.(08/01/15)
Switzerland-based GeNeuro has partnered with France-based Servier to develop and market GNbAC1 in Multiple Sclerosis (MS).
GNbAC1 is said to be the first drug being developed to address a causal factor of the disease, and holds the potential to radically change the way MS patients are treated.
A humanized monoclonal antibody, GNbAC1 targets the envelope protein of MS associated retrovirus, MSRV-Env, a member of the HERV-W family, the expression of which is usually silent but reactivated and expressed in MS lesions from an early stage in the disease.
GeNeur CEO François Curtin said: "This strategic agreement with Servier is a recognition of the innovative nature and huge potential of GeNeuro's technology.
"Combining GeNeuro's technical expertise with Servier's scientific, medical and financial resources will create an exciting new alliance to fuel the development of our unique approach, ultimately benefitting MS patients around the world."
As per terms of the agreement, GeNeuro will be responsible for the development of GNbAC1 until completion of Phase IIb, after which Servier can exercise the option to license the product for all markets excluding the USA and Japan.
Servier will pay around $47m to GeNeuro to complete the Phase IIb trail.
The company will cover the costs of the Phase III global development program and pay GeNeuro up to $408m in future development and sales milestones, as well as royalties on future sales, subsequent to exercising the option agreement.
According to Servier, GNbAC1 successfully completed Phase IIa trial, demonstrating an optimal safety profile and encouraging signs of efficacy on a first small cohort of patients.
Source: PBR © PBR 2014. Part of Progressive Digital Media Group Plc (05/12/14)
Researchers identify chemical compound that decreases effects of multiple sclerosis Multiple sclerosis (MS), an autoimmune disease of the brain and spinal cord, affects about 2.5 million people worldwide (400,000 in the United States). Affecting more women than men, it can be seen at any age, although it is most commonly diagnosed between the ages of 20 and 40.
An unpredictable disease that disrupts the flow of information within the brain and between the brain and the body, MS is triggered when the immune system attacks the myelin sheath, the protective covering around the axons of nerve fibers. The "demyelination" that follows causes a disruption of nerve impulses. As the protective sheath - best imagined as the insulating material around an electrical wire - wears off, the nerve signals slow down or stop, and the patient's vision, sensation and use of limbs get impaired. Permanent paralysis can result when the nerve fibers are completely damaged by the disease.
Given such debilitating effects, an aggressive search is on among scientists to find a cure for MS. Currently available therapies are only partially effective, however, in preventing the onset of permanent disability in MS patients. What would be immensely helpful is a drug that could minimize the degeneration of axons, thus reducing the rate and degree of MS progression. Better still would be if this drug could stimulate "remyelination," the re-sheathing of the axons, restoring fast and uninterrupted flow of nerve impulses.
Now a team of researchers, led by a biomedical scientist at the University of California, Riverside, reports in this week's issue of the Proceedings of the National Academy of Sciences that it has identified just such a drug in the lab: indazole chloride (Ind-Cl).
"This drug, which we administered on transgenic mice, can potentially halt the symptoms and reverse ongoing motor deficit due to MS," said Seema K. Tiwari-Woodruff, an associate professor in the UC Riverside School of Medicine whose lab led the study. "Our study shows that Ind-Cl can remyelinate axons which have gotten injured not just in MS but also traumatic brain injury and spinal cord injury."
Tiwari-Woodruff explained that Ind-Cl is a chemical compound that stimulates an estrogen receptor, ERβ, in the body. As is well known, pregnant women with MS get near-complete relief from MS symptoms in their third trimesters. Estrogen levels, which are high at this time, have neuroprotective benefits, alleviating the MS symptoms. After the birth of the baby, estrogen levels plummet in the mother and the MS symptoms return.
"This readily suggests that estrogen could be given to MS patients, except that high levels of estrogen are linked to breast and uterine cancers," said Tiwari-Woodruff, who joined UCR earlier this year. "Further, men would largely be reluctant to take estrogen due to its feminizing effects." Enter Ind-Cl, a small compound Tiwari-Woodruff has worked with for about two years. This structurally unique ligand turns on the body's estrogen receptors without the negative effects of excessive estrogen.
"More encouraging is that this compound works after disease onset," Tiwari-Woodruff said. "This makes it promising because a patient with MS typically first visits the doctor when he or she has noticed some motor deficits - loss of balance, inability to pick up an object, an impairment in vision. By this time though, the axons responsible for these motor functions have been massively affected. But if a drug can be administered at this point that can help the patient gain some relief from the disease and further damage, we'd be on to something.
"Ind-Cl is just such a drug in that it inhibits selective inflammation of the central nervous system," Tiwari-Woodruff added. "Our work on mice suggests that its effect is permanent. But perhaps more significant, Ind-Cl remyelinates, that is, it makes new sheaths around those axons that have not been lost for good. This means Ind-Cl not only inhibits inflammation but is capable of reducing axon degeneration and restoring neuronal function."
Tiwari-Woodruff's lab conducted electrophysiology tests to ensure that the remyelinated axons were retransmitting impulses. According to her, Ind-Cl can be developed for oral administration. To ensure that the remyelination her team observed in the MS mice was due to Ind-Cl and not to an immune response, the team administered Ind-Cl in mice whose oligodendrocytes, the cells responsible for remyelinating axons and myelin, were selectively decreased.
"We found that remyelination occurred more efficiently in such mice after they were given Ind-Cl," Tiwari-Woodruff said. "This means Ind-Cl works in two ways: through the immune system in terms of reducing brain and spinal cord inflammation, and directly by remyelinating the axons. This makes it an extremely promising drug."
Tiwari-Woodruff noted that Ind-Cl can be tweaked to make analogs that could work even better at alleviating MS symptoms. Her colleague John A. Katzenellenbogen, an organic chemist at the University of Illinois at Urbana-Champaign (UIUC) and a coauthor on the research paper, developed Ind-Cl. In addition, his group has already identified four analogs that the research team will soon test on MS mice.
"We expect some of these analogs will soon go to clinical trial," Tiwari-Woodruff said.
Source: Medical Xpress © Medical Xpress 2011-2014, Science X network (02/12/14)
ENDECE Neural announced the presentation of new, pre-clinical evidence that the company’s lead compound, NDC-1308, induces remyelination and increases forelimb grip strength in a validated animal model of demyelination. As presented in a poster session at the 2014 annual meeting of the Society for Neuroscience in Washington, D.C., the improvements with NDC-1308 therapy are linked to the drug’s unique ability to repair the myelin sheath of demyelinated axons (nerve fibres).
The data, presented by Steven H. Nye, Ph.D., Vice President of Discovery at ENDECE Neural, suggest that the remyelinating properties of NDC-1308 may benefit patients with secondary progressive multiple sclerosis (SPMS). ENDECE Neural has announced plans to initiate non-clinical investigational new drug (IND)-enabling studies of NDC-1308 and a first-in-humans Phase 1 clinical trial in 2015.
“We continue to be encouraged by the reproducible pre-clinical data generated for NDC-1308,” said Dr. Nye. “In addition to our previous knowledge about its mechanism of action, we now conclusively demonstrate the ability of NDC-1308 to repair the damaged myelin sheath in a cuprizone mouse model of demyelination. The grip-strength findings are especially encouraging, as this test may be translated to the clinic for measuring functional improvement in MS patients. We look forward to initiating clinical trials of this promising compound.”
Dr. Nye and colleagues reported that NDC-1308 induced significant remyelination in several brain regions using the cuprizone model of demyelination, in which the neurotoxicant cuprizone was used to remove the myelin sheath from the axons of mice. In addition, prophylactic treatment with NDC-1308 delayed the onset of clinical symptoms of MS in an experimental autoimmune encephalomyelitis (EAE) mouse model of brain inflammation while preserving neuronal cells, suggesting that it also exerts a neuroprotective activity. Chronic treatment with NDC-1308 was well-tolerated by the studied animals, suggesting it can be safely administered.
“All research to date indicates that NDC-1308 is ready to advance to IND-enabling and clinical studies,” commented James G. Yarger, Ph.D., Chief Executive Officer of ENDECE Neural. “The IND-enabling program has been designed to determine the safety and toxicity of NDC-1308 and appropriate starting doses for initiating Phase 1 studies in humans. We look forward to continuing the momentum from the pre-clinical studies as we enter the clinic with NDC-1308.”
NDC-1308 is a novel chemical entity designed to address the damage to the myelin sheath that occurs in patients with secondary progressive MS (SPMS), a common later phase of the disease that follows relapsing-remitting MS (RRMS). NDC-1308 is being developed for potential use either alone or in combination with other MS therapeutics that slow the progression of the disease. By dramatically up-regulating key genes in pathways leading to oligodendrocyte progenitor cell (OPC) differentiation and myelin synthesis, NDC-1308 appears to induce restoration of the lost myelin sheath that is believed to cause the devastating symptoms of MS. NDC-1308 is a small molecule that readily crosses the blood-brain barrier, allowing it to reach the tissues in the brain and spinal cord where promoting myelin production is needed. NDC-1308 works by inducing differentiation of OPCs into mature oligodendrocytes, cells that synthesize and maintain the myelin sheath. ENDECE Neural discovered NDC-1308, and owns the intellectual property surrounding the compound.
Source: Business Wire © 2014 Business Wire (19/11/14)
Genzyme, a Sanofi company, announced today enrollment of the first patient in a multicenter Phase II clinical trial to evaluate Genzyme’s investigational infusion therapy vatelizumab in patients with relapsing remitting multiple sclerosis (RRMS). The trial, called EMPIRE, is designed to assess the efficacy of vatelizumab vs. placebo in RRMS patients. The safety, tolerability and pharmacokinetics of vatelizumab will also be assessed.
Multiple sclerosis is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). Uncontrolled inflammation within the CNS leads to inflammatory damage that is associated with demyelinating lesions and neurodegeneration in patients with MS. Vatelizumab is a humanized monoclonal antibody that targets VLA-2, a collagen-binding integrin expressed on activated lymphocytes. The mechanism of action of vatelizumab is not known, although it is hypothesized to block VLA-2 on activated immune cells, leading to interference with collagen-binding in areas of inflammation, and thus may reduce the inflammatory cascade in MS.
“Continuous inflammation and neurodegeneration from the onset of multiple sclerosis can lead to significant disability,” said Eva Havrdova, MD, PhD, MS Center, Department of Neurology, First Medical Faculty, Charles University, Prague. “The EMPIRE trial should enable us to assess vatelizumab’s ability to impact the acute inflammatory components of MS and evaluate its potential as an effective MS treatment.”
Genzyme is developing vatelizumab in MS in partnership with Glenmark Pharmaceuticals. In addition to its marketed therapies, Genzyme has an MS R&D pipeline focused on investigational treatments to address unmet needs for relapsing and progressive forms of MS through research in selective immunomodulation, neuroprotection and remyelination.
“We are pleased to commence patient enrollment for our vatelizumab trial in relapsing MS,” said David Meeker, President and CEO, Genzyme. “This milestone demonstrates Genzyme’s long-term commitment to MS and aligns with our pipeline strategy to focus on areas of unmet need.”
EMPIRE is a global phase 2a/2b double-blind, randomized, placebo-controlled study assessing the efficacy, safety and dose-response of vatelizumab in patients with active RRMS. The study duration is 12 weeks. The study is expected to enroll 168 patients at 55 sites in 10 countries. For more information about the vatelizumab trial, visit www.clinicaltrials.gov.
Source: Finances © 2014 Finances International Ltd (03/11/14)
Concert Pharmaceuticals Inc. announced Phase 1 data of CTP-354, a novel, potentially first-in-class, non-sedating, once-daily oral treatment for spasticity. In this multiple ascending dose trial, no sedation or ataxia was observed with CTP-354 and the drug was generally well tolerated across all dose cohorts.
Concert expects to initiate a Phase 2 clinical trial evaluating CTP-354 in patients with spasticity associated with spinal cord injury by the end of 2014.
"We are very pleased to have completed our clinical evaluation of CTP-354 in this Phase 1 trial. We remain on track to advance the program into Phase 2 testing later this year, initially targeting spasticity in patients with spinal cord injury followed by the start of a Phase 2 trial in multiple sclerosis patients in early 2015," said Roger Tung, President and Chief Executive Officer.
The Phase 1 multiple ascending dose clinical trial was a randomized, double-blind, placebo-controlled study in 30 healthy volunteers. The primary objective of the trial was to evaluate the safety, tolerability and pharmacokinetics of 10-day repeat dosing of 2 mg, 6 mg and 12 mg of CTP-354.
Clinical highlights include: CTP-354 was generally well tolerated. There were no serious adverse events and no treatment discontinuations. The most common adverse events were dose-related mild and moderate dizziness and somnolence (drowsiness). No sedation or ataxia was observed at the doses evaluated. Across all doses, plasma half-life was approximately 20 hours at steady state. CTP-354 exposure was generally dose-proportional across daily doses ranging from 2 mg to 12 mg. Administration of CTP-354 under both fed and fasted conditions provided similar exposure, indicating that it can be dosed without regard to meals.
The company previously reported positive results from both a Phase 1 single ascending dose trial and a Phase 1 brain imaging trial as measured by positron emission tomography, or PET imaging. The long half-life and pharmacokinetic profile observed in the single ascending dose support once-daily dosing of CTP-354. In addition, CTP-354 provided high and sustained brain GABAA receptor occupancy levels in the brain imaging trial in both single and repeat doses.
Based on the results of the Phase 1 trials, Concert intends to advance CTP-354 into Phase 2 clinical evaluation later this year. The Phase 2 program is projected to include two trials: one evaluating spasticity associated with spinal cord injury and one evaluating spasticity associated with multiple sclerosis.
Source: NASDAQ © NASDAQ OMX Group, Inc (14/10/14)
San Francisco Bay Area-based Glialogix, Inc., a biopharmaceutical company that specializes in developing novel treatments for multiple sclerosis (MS), announced yesterday that they have closed a Sponsored Research Agreement with Fast Forward, a non-profit organization that aims to accelerate MS treatment development. Glialogix will receive funding for one of their pipeline products for neuroprotection, GLX1112, which has shown efficacy in slowing disability progression and potentially repairing neuronal damage — one of the main priorities of the National Multiple Sclerosis Society (NMSS).
Fast Forward, founded by the NMSS, will be supporting Glialogix through cutting-edge pharmacokinetic testing, preclinical models and mechanistic research on GLX1112. According to Thad Reeder, Ph.D., the company’s CSO and lead researcher for the drug, it has already shown promising results in progressive forms of MS.
Glialogix CEO, Mark Moore, Ph.D., explained that there is a great need for effective treatments for progressive MS, as this type tends to cause the most disability and does not respond to treatments indicated for relapsing MS. At present, while there are several drugs being tested for treating progressive forms of MS, most patients are treated with RRMS therapies, as these are the only drugs approved by the FDA for treating progressive MS in the United States. In other countries, progressive MS patients often have no access to therapies, and are forced to cope with symptoms and disabilities on their own.
Dr. Moore concluded by stating that he looks forward to collaborating with Fast Forward on the development of a viable progressive MS therapy, and is confident this new agreement is the boost GLX1112 is waiting for.
Source: Multiple Sclerosis News today © Copyright 2014 BioNews Services (02/10/14)
GeNeuro SA announced today positive results from a one-year, open-label extension of a Phase IIa study. GeNeuro tested its monoclonal antibody GNbAC1 in 10 multiple sclerosis (MS) patients, nine of which had primary or secondary progressive disease. GNbAC1 targets the MSRV-Env protein expressed by genes of endogenous retroviral origin, which GeNeuro believe plays a critical role in the pathogenesis of MS.
The long-term safety profile of GNbAC1 was confirmed, with excellent tolerability among patients following repeat administration, verifying results of the earlier Phase I study. With respect to clinical endpoints, the average Expanded Disability Status Score (EDSS), which measures disease progression, remained stable over one year. MRI analysis revealed that the brain images also remained stable and biomarkers associated with the target showed a consistent decline. These results confirm the safety and tolerability of GNbAC1 and support a positive pharmacodynamic response to the treatment. The positive results of this clinical study represent the successful first step in GeNeuro’s Phase II program. A proof-of-concept clinical study to test the efficacy of GNbAC1 in MS will follow in 2015.
Francois Curtin, CEO of GeNeuro stated: “We are very excited by the potential that GNbAC1 offers as a new avenue to treat MS patients. In addition to confirmation of long-term safety of the monoclonal antibody in patients, we have seen that the cohort of progressive MS patients was stable over one year from both clinical and MRI standpoints. Moreover, there is a clear decrease in the associated biomarkers supporting a positive pharmacodynamic response. This reinforces our conviction that GNbAC1 can completely transform the MS therapeutic landscape.” Curtin adds: “Preliminary results of this study presented at the American Academy of Neurology earlier this year generated a high level of enthusiasm among clinicians as they see that this treatment could bring new hope to patients as a safe therapy addressing a causal factor of the disease, breaking with the immunosuppressive logic of existing treatments.”
Source: PipelineReview.com © La Merie Publishing (04/09/14)
A new treatment under investigation for multiple sclerosis (MS) is safe and tolerable in phase I clinical trials, according to a study published August 27, 2014, in Neurology® Neuroimmunology & Neuroinflammation.
The phase I studies were the first to test the drug candidate in humans. Studies with animals showed that the drug, which is called anti-LINGO-1, or BIIB033, may be able to reverse the demyelination of the nerves. Anti-LINGO-1 blocks LINGO-1, a central nervous system protein that prevents myelination. Current treatments for MS work to reduce new damage to the brain, but do not repair new or past damage.
In MS, the body's immune system begins to attack the myelin that acts as insulation around the nerves in the central nervous system. This makes it more difficult for the nerves to send messages to and from the brain and spinal cord.
In the study, 72 healthy people without MS and 47 people with either relapsing-remitting MS or secondary progressive MS were given the drug or a placebo. The healthy participants received either a placebo or one dose of the drug by an infusion or an injection. The people with MS received either placebo or two intravenous doses of the drug two weeks apart. In both groups, participants received varying amounts of the drug, ranging from 0.1 mg/kg to 100 mg/kg.
The occurrence of side effects was similar for people who received the drug and those who received the placebo. Most side effects were mild to moderate and were not related to the drug. Side effects included headaches, upper respiratory infections and urinary tract infections. There were no serious side effects or deaths.
There were no significant changes in vital signs, EKGs or other safety tests of the drug.
Intravenous doses of 10 mg/kg and higher resulted in concentrations of the drug in the blood that were similar to or higher than the concentration that was associated with 90 percent of the maximum remyelination effect in studies with rats.
"With these results we have been able to start phase II studies to see whether this drug can actually repair the lost myelin in humans and have any effect on restoring physical and cognitive function and improving disability," said study author Diego Cadavid, MD, of Biogen Idec in Cambridge, Mass., which developed the drug. Cadavid is a member of the American Academy of Neurology.
Source: EurekAlert! Copyright ©2014 by AAAS (28/08/14)
Ireland-based biopharmaceutical firm Alkermes has started a Phase I clinical trial of ALKS 8700, a novel monomethyl fumarate (MMF) molecule being developed for the treatment of multiple sclerosis (MS).
The trial will assess the safety, tolerability and pharmacokinetics of several oral formulations of ALKS 8700 compared to both placebo and active control groups in approximately 125 healthy volunteers.
ALKS 8700 is designed to rapidly and efficiently convert to MMF in the body and provide differentiated features compared to the currently marketed dimethyl fumarate, Tecfidera.
Alkermes chief medical officer Elliot Ehrich said: "We expect the results of this study to be highly informative and determine the therapeutic utility and differentiating features of ALKS 8700.
"ALKS 8700 leverages Alkermes' expertise in prodrug chemistry and oral controlled-release formulations to offer potential differentiated tolerability and dosing for patients with MS."
The randomized, double-blind trial will investigate the pharmacokinetics and pharmacodynamics of multiple formulations and doses of ALKS 8700 and is designed to determine those suitable to progress into advanced clinical testing.
The start of the Phase I trial follows the company's filing of an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA), and the issuance of a composition of matter patent for ALKS 8700 from the US Patent and Trademark Office (USPTO) in March 2014, which is expected to provide patent protection into 2033.
Source: PBR Contract Research & Services © PBR 2010. Part of Progressive Digital Media Group Plc (21/07/14)
A common cold treatment and seven other drugs already approved for other conditions could help restore a protective coating eroded around neurons in multiple sclerosis patients, according to researchers led by a team at the University of California, San Francisco.
UCSF is spearheading a 50-patient clinical trial of the most promising drug — an over-the-counter antihistamine branded by Novartis as Tavist — that is expected to be completed by the end of the year.
Researchers warn MS patients not to rush out to buy Tavist, which also is sold generically as clemastine fumarate, because its safety and effectiveness is unknown in MS patients. What’s more, they don’t know what the proper dosage or treatment regimen of the drug might be for multiple sclerosis.
Still, the emergence of Tavist and the seven other drugs is a huge potential win for MS patients and researchers who only 14 months ago launched a new method for quickly screening 1,000 drugs already approved by the Food and Drug Administration for other conditions.
“A major unmet need in the development of therapeutics for repair in MS has been the ability to screen compounds in a high-throughput manner,” Jonah Chan, a neurology professor and senior author of a paper that appeared Sunday in the Journal Nature, said in a press release.
The research group includes scientists from Third Military Medical University in Chongqing, China, the University of Cambridge in the United Kingdom, and Trianja Technologies, north of Dallas.
Multiple sclerosis is a central nervous system disease in which the immune system attacks healthy nerve tissue, destroying the fatty myelin sheaths that are meant to protect the cells. By disrupting the electrical signals from the central nervous system to the body, MS leads to muscle weakness, worsening vision, poor balance or coordination, memory problems and other symptoms.
About 2.3 million worldwide have MS, according to the Multiple Sclerosis International Federation.
Researchers for years have focused potential treatments on soothing the inflammation caused by the intermittent and progressively worsening immune system attacks. Over the past decade, however, they have focused much of their work on stopping the erosion of myelin and, potentially, restoring myelin and protecting neurons.
Only last month drug maker Roche, the parent company of South San Francisco-based Genentech Inc., and Menlo Park-based venture capital firm Versant Ventures formed a company focused on regrowing myelin in MS patients. The basis for that company is a screening technology developed by Chan and his colleagues at UCSF.
The new automated system crafted by Chan’s research group, supported by donations to UCSF's MS Research Group, UCSF's Clinical and Translational Science Institute and the National Multiple Sclerosis Society, quickly tested if 1,000 FDA-approved drugs had any effect on oligodendrocyte precursor cells. So-called OPCs are the cells from which oligodendrocytes are derived in the brain and spinal cord, and it is those specialized oligodendrocytes that myelinate extensions of neurons that transmit signals to the brain. All eight drugs identified by the research team have a common mechanism of action — blocking a specific receptor — but clemastine was the most effective, according to UCSF. But there are five types of that receptor expressed in the nervous system and researchers want to know if clemastine blocks a single receptor of a combination.
In the ongoing Phase II trial — the second of the typically three-stage FDA drug-approval process — researchers mainly want to see if clemastine has an effect on MS patients’ vision at one, three and five months of treatment.
Patients in the trial will receive one four-milligram tablet of clemastine or a placebo twice a day for three months.
Source: San Francisco Business Times © 2014 American City Business Journals (07/07/14)
A casual conversation in a hockey locker room prompted a business partnership that may eventually help people suffering from multiple sclerosis and other neuro-degenerative diseases.
Joseph S. Erlichman, a biology professor at St. Lawrence University, and Mark L. Brackett, president of the Kinney Drug Inc. Foundation, are working with others to develop a drug to treat diseases such as MS and Amyotrophic Lateral Sclerosis, also known as Lou Gehrig’s Disease.
After playing hockey one evening, the two men discussed research that Mr. Erlichman and a few of his colleagues were conducting on live brain slices from mice.
The study focuses on observing how the compound cerium oxide affects neuro-damage that’s taken place in the mice. The rodents are observed after they’re placed on a motor-skill apparatus like a treadmill or balance beam to see if they show improvement after taking the cerium oxide.
For the past several years, students from SLU have been involved in that part of the research.
Mr. Erlichman said the results have been promising so far.
“We’ve been accruing an enormous amount of data,” he said. “We’ve found this has the potential to mitigate or decrease tissue damage or disease progression in a wide variety of pathologies.”
Essentially, the compound is effective at neutralizing free radicals that are associated with many pathological diseases, Mr. Erlichman said.
For multiple sclerosis, the compound appears to be as effective as Gilenya, a drug now used to treat the disease in humans, he said.
“We have also used the nanoparticles in the treatment of a mouse model of ALS with promising results,” he said.
In 2009 Mr. Brackett and Mr. Erlichman created the company Neuroredox, with Mr. Brackett serving as its chief executive officer.
Later they teamed up with Cerion Enterprises, a Rochester-based company, to create a new joint venture company, erion NRx, which will continue the necessary steps involved with developing the drug.
Other SLU professors have also been involved in the research, including William DeCouteau, Ana Y. Estevez, Karin Heckman and Matthew C. Skeels.
Upcoming steps include receiving approval from the Food and Drug Administration to test the drug’s effectiveness on humans. Determining whether the drug is toxic to humans will be a main factor in determining if it can be marketed to a pharmaceutical company and then sold to the public, Mr. Brackett said.
Finding a pharmaceutical company to invest in the product and applying for federal funding are other hurdles.
“You have to get all the ducks in a row,” Mr. Brackett said. “We have hired a consultant who has taken other drugs to market.”
Mr. Brackett, a former pharmacist, said he has been interested in neurological diseases for many years.
“These diseases cause a great deal of devastation and pain to families. We think we can help that,” he said.
Source: Watertown Daily Times (27/02/14)
Potential 'cure' for multiple sclerosis to be tested The National Center of Neurology and Psychiatry has developed a drug that it says might provide a cure to multiple sclerosis.
The center announced Monday that it will start a three-month clinical trial from March on nine patients. If the drug’s efficacy is confirmed, it will move on to a large-scale trial.
“We are hopeful as preliminary studies have produced very good results,” said Takashi Yamamura, head of the immunology department responsible for the drug’s development. About 2.5 million people around the world are estimated to suffer from the disease, which causes symptoms such as numbness, motion problems and vision loss. In Japan, there are an estimated 15,000 sufferers, including many young women, and the number is growing.
The autoimmune disease occurs when lymphocyte immune cells misidentify the body’s own cells as foreign. They attack nerve cells, causing inflammation and destroying them.
The drug developed by Yamamura stimulates a type of immune cell that softens the attacks by lymphocytes and creates a protein that suppresses inflammation. In the clinical trial, the drug will be drunk in powder form dissolved in water, according to the center.
Source: THE JAPAN TIMES © THE JAPAN TIMES LTD (26/02/14)
Quite often, the development of novel therapies for one disease indication later gives rise to its application for other diseases as well. In the case of Multiple Sclerosis treatment, the non-profit Myelin Repair Foundation (MRF) may have identified a proven drug for hypertension that could be used to stimulate repair and protect the brain in MS patients.
The discovery will be further explored in a new clinical trial that will be facilitated through a Cooperative Research and Development Agreement (CRADA) between the MRF and the National Institutes of Health’s National Institute of Neurological Disorders and Stroke (NINDS) at the NIH Clinical Center, which will seek to assess the use of hypertension drug MRF-008 as a potential neuroprotective therapeutic for Multiple Sclerosis.
The collaboration between the MRF and NIH is a unique one, since the Myelin Repair Foundation is a true non-profit research group that directs its research goals from a completely practical, patient-driven perspective, seeking to develop tangible Multiple Sclerosis treatments that can be realistically developed and commercialized. The Foundation’s commitment to publishing provable, reproducible results, together with the vast talent and resources at the NIH, bode well for fully exploring the efficacy of MRF-008 patients.
Scott Johnson, CEO, President and Founder of the Myelin Repair Foundation and himself a Secondary Progressive MS patient seeking viable, effective treatments in the near future, commented on the Foundation’s new collaboration with the NIH and what it could mean to future MS treatment options, stating, “As a non-profit organization beholden to patients, not profits, we are uniquely positioned to advance MRF-008, a generic drug identified by the MRF academic consortium, forward as a novel therapeutic candidate to stimulate repair for multiple sclerosis,” adding that, “With the NIH’s eminent expertise in MS clinical trials, we have found an exemplary partner to conduct the research necessary to assess MRF-008. With world-class advisors, academic scientists, industry partners and this opportunity to collaborate with NIH scientists, we remain on track to develop and deliver the next generation of MS therapeutics for patients.”
The MRF delivers substantial results from its research through the Foundation’s Accelerated Research Collaboration™(ARC™) model, which is designed to accelerate promising therapeutics to market through streamlining the research and development of promising compounds from the lab to the clinic, and ultimately to Multiple Sclerosis patients. MRF leveraged its ARC model to forge its new relationship with the NIH on studying the viability of MRF-008, and will continue to utilize the platform to facilitate partnerships between top academic scientists, pharmaceutical partners, and other key biotech and life sciences influencers.
The Myelin Repair Foundation will work closely with the NIH to assess MRF-008 as a therapeutic candidate in an MS clinical trial. MRF-008 is a generic FDA-approved compound for the treatment of hypertension identified by the Myelin Repair Foundation’s academic research consortium as a novel drug repurposing candidate for neuroprotection to stimulate MS repair. Dr. Irene Cortese, M.D. and Dr. Daniel Reich, M.D., Ph.D. will lead the research study at the NIH.
Visit the Myelin Repair Foundation to learn more about MRF-008.
Source: Bionews Texas (28/01/14)
A new clinical trial is underway for individuals who have secondary progressive multiple sclerosis (SPMS). Patients with SPMS generally have had relapsing-remitting MS, but now are having attacks that are less frequent and less well defined. Patients don’t generally recuperate from these attacks and disabilities begin set in. It is reported that 80% of patients with relapsing-remitting MS eventually develop secondary progressive Multiple Sclerosis, and this process tends to begin 15 or so years after being diagnosed with MS.
A Phase 3 trial will be held worldwide and is recruiting 1,530 individuals who have secondary progressive multiple sclerosis (SPMS) to test the safety and effectiveness of an experimental oral therapy siponimod (BAF312) manufactured by Novartis Pharmaceuticals AG versus an inactive placebo.
The drug, siponimod, is an immune system-modulating treatment designed to be a more selective sphingosine 1-phosphate receptor modulator than Gilenya (fingolimod, Novartis). Gilenya was approved in 2010 for adults with relapsing forms of MS to decrease the frequency of relapses to delay accumulation of physical disabilities.
In a Phase 2 trial, siponimod demonstrated safety and efficacy on MRI scans in individuals with relapsing-remitting MS. Information on this trial is available in The Lancet Neurology, Early Online Publication, June 11, 2013 . Siponimod is believed to act by retaining specific white blood cells in lymph nodes keeping then out of circulation and from getting into the central nervous system. This oral drug can also enter the central nervous system where it may have a direct anti-inflammatory or neurobiological effect. The secondary progressive multiple sclerosis (SPMS) study is currently recruiting participants and is sponsored by Novartis Pharmaceuticals under clinical trial identifier NCT01665144. The purpose of this phase 3 trial is to evaluate the safety and efficacy of Siponimod (BAF312) versus placebo in a variable treatment duration in patients with SPMS.
Patients will be randomized to receive Siponimod (BAF312) for a duration of 23 to 42 months with a maximum of 60 months. Patients who meet all inclusion and none of the exclusion criteria will be treated with BAF312 daily. Eligibility age runs 18 to 60 years and will include both sexes.
Inclusion criteria includes a prior history of relapsing remitting MS, SPMS defined as progressive increase of disability over a least 6 months, EDSS score of 3.0 to 6.5 and relapse of corticosteroid treatment within 3 months.
Of the 1,530 participants, 1,050 will take siponimod and 510 will take the placebo every day for up to 60 months. The primary outcome will look at the delay in to confirmed disability progression as measured by the EDSS scale. This scale has been in MS studies for more than 4 decades and is based on the presence of certain symptoms in a typical neurological exam. Secondary outcomes include disease activity as observed on MRI scans, scales that measure mobility, relapse rates, adverse events and abnormalities on lab tests.
Source: Bionews Texas (27/01/14)
An antioxidant designed by scientists more than 12 years ago to fight damage within human cells can treat symptoms in mice that have a multiple sclerosis-like disease, a new study led by an Indian-origin researcher has found.
The antioxidant - called MitoQ - has shown some promise in fighting neurodegenerative diseases. But this is the first time it has been shown to significantly reverse an MS-like disease in an animal.
The discovery by Oregon Health & Science University could lead to a new way to treat multiple sclerosis, which affects more than 2.5 million people worldwide.
Multiple sclerosis occurs when the body's immune system attacks the myelin, or the protective sheath, surrounding nerve fibres of the central nervous system. Some underlying nerve fibres are destroyed.
Resulting symptoms can include blurred vision and blindness, loss of balance, slurred speech, tremors, numbness and problems with memory and concentration.
The antioxidant research, published in the journal Biochimica et Biophysica Acta Molecular Basis of Disease, was led by P Hemachandra Reddy, an associate scientist in the Division of Neuroscience at OHSU's Oregon National Primate Research Center.
In the study, researchers induced mice to contract a disease called experimental autoimmune encephalomyelitis, or EAE, which is very similar to MS in humans.
They separated mice into four groups: a group with EAE only; a group that was given the EAE, then treated with the MitoQ; a third group that was given the MitoQ first, then given the EAE; and a fourth "control" group of mice without EAE and without any other treatment.
After 14 days, the EAE mice that had been treated with the MitoQ exhibited reduced inflammatory markers and increased neuronal activity in the spinal cord - an affected brain region in MS - that showed their EAE symptoms were being improved by the treatment.
The mice showed reduced loss of axons, or nerve fibres and reduced neurological disabilities associated with the EAE.
The mice that had been pre-treated with the MitoQ showed the least problems. The mice that had been treated with MitoQ after EAE also showed many fewer problems than mice who were just induced to get the EAE and then given no treatment.
"The MitoQ also significantly reduced inflammation of the neurons and reduced demyelination. These results are really exciting. This could be a new front in the fight against MS," Reddy said.
"It appears that MitoQ enters neuronal mitochondria quickly, scavenges free radicals, reduces oxidative insults produced by elevated inflammation, and maintains or even boosts neuronal energy in affected cells," said Reddy.
The hope has been that MitoQ might help treat neurodegenerative diseases like Alzheimer's and Parkinson's. Studies evaluating its helpfulness in treating those diseases are ongoing.
Source: Business Standard Copyrights © 2014 Business Standard Ltd (02/01/14)
Revalesio Corporation has announced a new collaboration with noted neurologist Dr. Roland Martin, Head of Neuroimmunology and MS Research at the Department of Neurology, University Hospital Zurich. Dr. Martin will be conducting a Phase IIa clinical trial of RNS60 in patients with relapsing-remitting multiple sclerosis (RRMS or MS). With 30 years experience, Dr. Martin is a recognized leader in the field of neuroimmunology and multiple sclerosis research.
The study will compare measurements of disease activity and progression in patients with RRMS during 6-months treatment with RNS60. The open label study will enroll 15 patients and evaluate the use of RNS60 by intravenous administration compared to patient's pre-treatment disease activity. The main outcome of the study will be the reduction of inflammatory activity in the brain as measured by Gd contrast-enhacing MRI lesions. Additional measures include progression of disability and biomarkers for RNS60 and general inflammation. The study will be conducted at the University Hospital Zurich in Switzerland and at Innsbruck Medical University in Innsbruck, Austria.
"Our MS development work with RNS60 has been an extraordinary process of discovery and pioneering research," said Dr. Richard Watson, Revalesio's Chief Science Officer. "We have published much of our data regarding RNS60's mechanisms in the pre-clinical models and are pleased to have Dr. Martin as a collaborator and to see RNS60 advance into the clinic for MS. We are hopeful this study will provide an efficacy signal that demonstrates RNS60's therapeutic potential and informs future clinical research."
RNS60 has been tested in numerous pre-clinical models of MS and has shown the ability to halt disease progression by limiting glial infiltration (inflammation in the brain), protecting myelin and enriching the regulatory T-cell (TREG) populations in animals treated with RNS60. Data from these pre-clinical models can be found in the academic journal PLOS ONE.
About RNS60 Revalesio has pioneered the use of RNS60 as a therapeutic that alters whole cell conductance through effects on voltage-sensing membrane-bound proteins, thereby modulating the activity of G protein-coupled receptors and the secretion of cytokines, chemokines resulting in decreased inflammation and cell death. RNS60 contains charge-stabilized nanostructures (CSN) that are created by subjecting normal saline to Taylor-Couette-Poiseuille (TCP) flow. RNS60 has demonstrated a reduction in inflammatory responses that are linked to numerous diseases, including neurodegenerative, respiratory and cardiovascular diseases.
Source: The Sacramento Bee Copyright © The Sacramento Bee 2013 (11/11/13)
GeNeuro announced today that its GNbAC1 humanized monoclonal antibody was found to have a very good safety profile when administered to patients with relapsing and progressive forms of Multiple Sclerosis as part of a Phase 2a study. GNbaC1 is a first-in-class monoclonal antibody targeting a toxic protein of endogenous retroviral origin that has been identified as a potential key factor in the onset and development of multiple sclerosis. Enrollment of patients into a multinational Phase 2b study is expected to begin during the first half 2014.
“The safety data achieved in this Phase IIa study is excellent and supports the future development of GNbaC1 in both relapsing remitting and progressive MS,” commented François Curtin, CEO of GeNeuro. “While presenting at the recent ECTRIMS1 congress in Copenhagen last month, GeNeuro’s approach was highlighted as one of the most innovative and promising new treatments in clinical development against MS as it specifically targets a potential causal factor of the disease.”
In the completed Phase 2a clinical study including a six-month extension, conducted to establish safety and pharmacokinetics, GNbAC1 demonstrated very good safety following repeated administration at 2 mg/kg and 6 mg/kg. The repeated administrations did not affect the immune system, the TLR4 function was preserved and no signs of induction of immunogenicity were observed.
About the ENV toxic Protein and its role in Multiple Sclerosis and other pathologies
The sequencing of the human genome revealed human endogenous retroviruses (HERV) represent more than 8% of the human genome and result from the integration of exogenous retroviruses DNA during the primate evolution.
The Multiple Sclerosis associated retrovirus (MSRV) is a member of the HERV-W family and was initially isolated in cell cultures from patients affected with Multiple Sclerosis in the 90’s. MSRV is normally latent in the genome of individuals, but it can be re-activated by certain co-factors to expresses a pathogenic protein, MSRV-Env. Recent evidence has demonstrated that this ENV-protein is expressed in MS lesions from an early stage, is pro-inflammatory and inhibits remyelination.
Source: Rock Hill Herald Online Copywrite Rock Hill Herald 2013 (04/11/13)