Phase 1 trial completed(01/04/15)
Vaccinex, Inc. has today announced the successful completion of a multicenter phase 1, randomized, double-blind, placebo-controlled, single ascending-dose safety and tolerability study in adult patients with multiple sclerosis.
According to reports, a total of 50 patients took part in the trial to determine the safety and tolerability of the drug currently known as VX15/2503, a monoclonal antibody discovered, characterised, and successfully tested by Vaccinex in preclinical models of multiple sclerosis and Huntington's disease.
VX15/2503 was found to be well tolerated at dose levels of up to 20 mg/kg with no reports of treatment-related serious adverse events.
No maximum tolerated dose (MTD) was determined and no dose-limiting toxicities (DLTs) were observed.
A phase 2 clinical trial of the VX15/2503 antibody in Huntington's Disease is planned to begin in the first half of 2015.
Source: BioSpace Copyright © 2015 BioSpace.com (01/04/15)
Could molecules prevent MS damage?(09/03/15)
Researchers at the Icahn School of Medicine at Mount Sinai have identified new compounds that could protect from multiple sclerosis-related damage, based on studies in mice with nervous system damage, mimicking MS. The study appeared in the journal Nature Neuroscience.
Jeffery Haines, PhD, a post-doctoral fellow at Mount Sinai and the study’s lead author commented, “The compounds identified in this study, when administered orally, both reduced the inflammation that is a hallmark of multiple sclerosis and protected against the nerve cell damage seen in mouse models of the disease. The multiple sclerosis drugs currently on the market and being tested elsewhere seek to reduce the immune attack on cells, but none target neurodegeneration nor do they work to restore nerve cell function. The findings of this new study represent an exciting step in the process of advancing new oral treatment options.”
A molecule called XPO1 (also called CRM1,) may be involved in multiple sclerosis as well as other diseases. The researchers decided to target this molecule.
They tested whether drugs designed to block XPO1/CRM1 could stop MS in mouse models. Two drugs were identified, KPT-276 and KPT-350, that acted on XPO1/CRM1. The medications seemed to protect cells from what is called free-radical damage — the production of damaging ions faster than the body can remove them. Free radical damage may be one way that the nervous system is affected in MS. Not only did the medications block free radical damage, they also prevented inflammation by stopping cells involved in inflammation from dividing. Immune cells can cause inflammation, which may be positive in infection, but is damaging in MS in which the immune cells attack the body’s own myelin. Stopping immune cells in the case of MS is therefore positive.
The medications helped the mice, which lost movement due to an experimental treatment that damaged myelin, to regain some movement as well.
Patrizia Casaccia, MD, PhD, Professor of Neuroscience, Genetics and Genomic Sciences at Mount Sinai and senior author of the study noted, “The study results elucidate the molecular mechanisms underlying disease progression in multiple sclerosis models, providing a basis for future clinical trials to determine safety and efficacy of these chemical agents in humans with demyelinating disorders.”
Source: Multiple Sclerosis News Today © BioNews-tx.com 2015 (09/03/15)
A team of scientists have uncovered a molecule that fights one of the main causes of inflammatory diseases and could be the key to improved treatments for diseases like Alzheimer's, arthritis and multiple sclerosis. The research team, led by Trinity and the University of Queensland Australia, showed the molecule, MCC950, could suppress the key activator in inflammatory diseases, NLRP3. The finding also confirms that inflammatory diseases all share a common process, even though the part of the body becoming inflamed might differ.
Researcher Luke O'Neill said drugs like aspirin or steroids can work in several diseases, but can have side effects or be ineffective, and what they have found is a potentially transformative medicine, which targets what appears to be the common disease-causing process in a myriad of inflammatory diseases. There is huge interest in NLRP3, both among medical researchers and pharmaceutical companies, and they feel their work makes a significant contribution to the efforts to find new medicines to limit it. MCC950 can be administered orally and will be cheaper to produce than current protein-based treatments, which are given daily, weekly, or monthly by injection.
More importantly, the new molecule also remains in the body for a shorter duration, allowing clinicians to stop the anti-inflammatory action of the drug if the patient ever needed to switch their immune response back to 100 percent, in order to clear an infection. So far, the results have shown great promise for blocking multiple sclerosis in a model of the disease, as well as in sepsis where, in response to bacteria, potentially fatal blood poisoning occurs. However, the target for MCC950 is strongly implicated in diseases such as Alzheimer's disease, atherosclerosis, gout, Parkinson's disease and rheumatoid arthritis, which means it has the potential to treat all of these conditions. The study is published in medical journal Nature Medicine.
Source: dna © 2015 Diligent Media Corporation Ltd (18/02/15)
Alkermes plc has reported positive top-line data from a phase I study on its experimental MS drug, ALKS 8700. ALKS 8700 is a novel monomethyl fumarate (MMF) molecule being developed for the treatment of MS.
The three-part, randomized, double-blind phase I study was conducted to evaluate the safety, tolerability and pharmacokinetics (PK) of several oral formulations of ALKS 8700 as compared to both placebo and active control groups in 104 healthy volunteers.
Data from the phase 1 study revealed that ALKS 8700 provided MMF exposures with less variability and improved gastrointestinal (GI) tolerability when compared to Tecfidera. Patients reported lower GI-related adverse events when treated with ALKS 8700 (8.3 per cent) as compared to Tecfidera (41.7 per cent). Moreover, the candidate was also found to be well tolerated during the course of the study.
Encouraged by the positive results from the phase I study, Alkermes plans to conduct a meeting with the FDA and move a twice-daily dose of ALKS 8700 into a pivotal development program this year.
Source: Zacks Copyright © 2015 Zacks Investment Research (11/02/15)
Drug development company Rock Creek Pharmaceuticals has announced a new clinical trial application with the Medicines Healthcare Products Regulatory Agency (MHRA) has been approved. The company is set to proceed with a Phase I study of Anatabine Citrate, a chemical that is found naturally in aubergine, potatoes, green tomatoes and other members of the Solanaceae family of plants, as well as in tobacco and tobacco smoke. The chemical is known for its anti-inflammatory properties unique from other anti-inflammatory drugs on the market, and may benefit patients with multiple sclerosis (MS).
The Phase I study will evaluate Anatabine’s pharmacokinetic profile in the form of modified release formulation prototypes, and its safety and tolerability profiles in healthy volunteers. The first two parts will involve an open-label, non-controlled, single-dose study on 14 healthy participants, using six formula variations, with each administered dose spaced 7-14 days apart. The variations will be distinct in dose and duration of therapeutic action. This will allow the company to determine which formulation is most ideal, based on safety. The third and last part of the Phase I study will be a double-blind, placebo-controlled, seven-day multiple dose study of the identified optimal formulation in healthy subjects.
“We are delighted to have been granted regulatory approval to begin our Phase I studies in the UK. This is the first clinical phase for our lead drug and will focus on safety and tolerability of six different formulations, five of which have modified release profiles and are of different doses. We look forward to generating our first human clinical data under this CTA,” said Rock Creek Pharmaceuticals CEO Dr Michael Mullan.
Rock Creek’s UK-based partner, Quotient Clinical, is set to begin enrollment of healthy subjects this month. While the company expects the study to stretch well into August, they expect to have a significant amount of research findings by mid-2015. Rock Creek also announced Quotient Clinical will be utilizing its RapidFACT® (Rapid Formulation development And Clinical Testing) service to hasten the development of these novel, oral, modified release formulations that have been co-developed between the two companies.
Source: Multiple Sclerosis News Today © BioNews-tx.com 2015 (03/02/15)
Acorda Therapeutics has today announced safety and tolerability data from a Phase 1 clinical trial of rHIgM22, a remyelinating antibody being studied for the treatment of multiple sclerosis. The trial, which followed participants for up to six months after receiving a single dose of rHIgM22, found no dose-limiting toxicities at any of the five dose levels studied. Based on this, the Company intends to advance clinical development of rHIgM22.
“We’re encouraged by the outcome of this trial, which showed that rHIgM22 was well-tolerated at all of the dose levels we studied,” said Anthony Caggiano, M.D., Ph.D., Acorda’s Senior Vice President of Research and Development. “We are currently developing the protocol for our next Phase 1 clinical trial of rHIgM22. The data from this study will help inform the design of the next trial, which will enroll people with MS who are experiencing an active relapse.”
This was a multi-center, double-blind, randomized, placebo-controlled study designed to evaluate safety, tolerability, pharmacokinetics, and immunogenicity of a single dose of rHIgM22 in participants with any type of MS who were clinically stable for at least three months. All participants remained on their existing MS treatment regimens, including disease-modifying therapies.
The first part of the study included five cohorts, with each cohort receiving a higher dose of rHIgM22 than the previous one. Each cohort consisted of 10 participants (eight receiving drug, two receiving placebo), who were followed for three months after receiving a single dose of study medication. In the second part of the study, 21 participants were randomized to receive placebo or one of the two highest doses of rHIgM22 from the first part of the study. These participants were followed for six months to assess safety and tolerability. The second part of the study also included several exploratory clinical, imaging and biomarker measures, which are still being analysed. The study was not powered to determine statistical significance on these measures.
Additional details from the trial will be presented at future medical meetings.
Across all of the study groups, 55 participants received one of the five doses of rHIgM22 and 17 received placebo (no sample size power calculation was used to determine the number of participants in each group). There were no dose-limiting toxicities and no serious adverse events (SAE) in any of the five rHIgM22 dose levels in the study. There was one SAE of squamous cell carcinoma in a placebo-treated participant.
The most commonly observed adverse events (>5 per cent in the combined rHIgM22 treatment groups) reported in the study were: headache, contact dermatitis, MS relapse, infusion site hematoma, fatigue, arthralgia, back pain, muscular weakness, neck pain, pain in an extremity, pruritus, contusion, and flushing. No participants withdrew due to adverse events.
No safety signals were identified by standard clinical MRI evaluations, or standard clinical, laboratory or ECG assessments.
rHIgM22 is a recombinant human monoclonal antibody identified in the laboratory of Moses Rodriguez, M.D. at Mayo Clinic. In preclinical studies, rHIgM22 has been found to protect oligodendrocytes and stimulate them to repair areas of demyelination. rHIgM22 treatment also resulted in sustained improvements in motor activity in preclinical models.
Source: Finances © 2015 Finances International Ltd. (02/02/15)
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)