treatment

Topas Therapeutics and Eli Lilly and Company are teaming up to develop compounds that could be used to treat inflammatory and autoimmune diseases, such as multiple sclerosis and diabetes. The compounds, based on a Topas technology platform, will be aimed at restoring immune tolerance. Immune tolerance refers to the immune system being unresponsive to certain antigens — for instance, the body’s own proteins. Without immune tolerance, the body can generate an excessive immune response that prompts the immune system to attack healthy organs or tissue — a process called autoimmunity Under the multiyear agreement, Topas will receive research and development funding. It will also receive financial rewards from the success of any drug developed under the collaboration. The agreement will give Lilly the option to license all therapies created under the collaboration, and to develop them further. "We are excited to be working with Lilly to generate drug candidates using our proprietary technology," Timm Jessen, the CEO of Topas Therapeutics, said in a press release. "We expect this work to support the value of our approach" of triggering immune tolerance against antigens, he said. The fact that an important pharmaceutical company like Lilly is interested "in our technology, we believe, supports the strong commercial potential of our work." Topas develops compounds against autoimmune reactions — that is, situations in which the immune system attacks healthy parts of the body. It is already developing treatments for multiple sclerosis, type 1 diabetes, celiac disease, and other autoimmune disorders. While the majority of such therapies try to shut down the immune system, Topas’ approach is to trigger antigen-specific immune tolerance. This allows the body to regain control over an excessive immune response, while sparing the body's normal immunity. Topas links its compounds to tiny nanoparticles that liver sinusoidal endothelial cells can absorb. The liver cells are the first place where immune T-cells can learn what the body should not fight against. In studies of mice with multiple sclerosis, a single injection of nanoparticles containing peptides found in neurons triggered a potent protective effect, improving the disease's symptoms and blocking its progression. Peptides are components of proteins. "Lilly is committed to be an innovation leader in immunology," said Dr. Thomas F. Bumol, senior vice president of biotechnology and immunology research at Lilly. "Topas has a very novel approach to immune tolerance induction, which we would like to see successfully applied to certain disease-relevant antigens. We look forward to working together with Topas on their unique platform."

Merck’s Mavenclad tablets significantly improve quality of life among relapsing multiple sclerosis patients while reducing the number of relapses, according to new analyses of previously unpublished data from clinical trials assessing the drug. This new data, published in the Multiple Sclerosis Journal, come just as the European Commission ponders whether to approve the once- rejected therapy to treat relapsing forms of MS. Its decision is expected later this month, seven years after a perceived increased of cancer risk led the European Medicines Agency (EMA) to block Mavenclad. In 2011, the U.S. Food and Drug Administration (FDA) rejected the medication, forcing its eventual withdrawal from the Australian and Russian markets, where it had already been licensed. For the study, researchers at Queen Mary University of London used data obtained from the EMA through a Freedom of Information request. They analyzed data from the Phase 3 CLARITY trial, which compared Mavenclad to placebo. The trial's 1,326 participants completed a quality-of-life questionnaire that focused on disease aspects such as mobility, self-care, usual activities, pain or discomfort, and anxiety. After two years, those on Mavenclad had significantly improved their quality of life compared to the control group, particularly in terms of self-care. Mavenclad also helped mobility, which might be related to its ability to prevent relapses and delay progression, researchers said. While researchers assessed quality of life using two different questionnaires, patients had only completed one in sufficient numbers to allow for a solid analysis. The other quality-of-life tool provided researchers with numerically positive results, but the low number of responses made the result difficult to interpret. This wasn't the first time QMUL researchers have contributed in this way to knowledge of Mavenclad in MS. In 2015, they used a Freedom of Information request to obtain data showing that Mavenclad was not related to increased cancer risk. “Cladribine seemed to have such excellent potential as a treatment for MS that we thought it was tragic the development program was shelved, and significant parts of the clinical trial data remained unpublished,” study leader Klaus Schmierer, a neurologist at both QMUL and Barts Health NHS Trust, said in a press release. “In addition to the drug being highly effective, well tolerated and safe as far as short-term studies can show, we now know it also improves patients’ quality of life. The new results seemed so clear, we felt it was extremely important to publish and share these data." Mavenclad has now been studied in some 2,700 patients with relapsing MS in the Phase 3 trials CLARITY, CLARITY EXTENSION, and ORACLE-MS, as well as the Phase 2 ONWARD trial, and the ongoing long-term study PREMIERE. The treatment differs from most other oral MS therapies in that a short treatment course — a maximum 20 days — triggered effects that were upheld for two years. Studies of Mavenclad’s mechanisms suggest the drug gets such results by resetting the immune system. In June 2017, the EMA's Committee for Medicinal Products for Human Use urged the European Commission to approve Mavenclad. Merck also plans to seek U.S. approval for its therapy and is now in talks with the FDA about Mavenclad's future.

Older Immunosuppressants May Increase MS Patients’ Cancer Risk, Study Reports We’re talking about some pretty harsh immunosuppressant drugs here: azathioprine, mitoxantrone, and possibly cyclophosphamide. Unlike newer drugs, targeted to specific cells, these knocked out an entire spectrum of immune cells when they were administered. If you’ve used…

of the neurons.

The state where I live has legalized medical marijuana (MMJ) and it’s getting ready to open state-licensed marijuana dispensaries. So, I’ve been thinking about using MMJ to treat some of my MS symptoms. How can MMJ help MS patients? A 2012 study by researchers at the University…

I stood at the front door of my house and could only shake my head as I watched the backhoe digging a deep trench in my yard. A sewer line malfunction created a mess in my basement and it turned out to be a broken clay pipe in…

Health Canada has approved Ocrevus for the treatment of adults with relapsing-remitting multiple sclerosis (RRMS) with active disease, Roche Canada announced. The approval followed the positive results from the Phase 3 OPERA studies, which evaluated the safety and efficacy of Ocrevus in 825 patients with RRMS. The OPERA 1 and OPERA 2 trials showed that Ocrevus significantly reduced disease activity and disability progression of RRMS patients, with annual relapse rates falling by almost half. Moreover, Ocrevus outperformed Rebif, the standard of care in MS, in slowing worsening of disability and significantly reducing lesions seen on MRI scans over a two-year treatment period. "Ocrevus is a major addition to the treatment options available for MS. The RRMS Ocrevus clinical trial data show a significant reduction in relapses and disease progression, as well as a good safety profile," Daniel Selchen, a neurologist and head of the Division of Neurology at St. Michael's Hospital in Toronto, said in a press release. "For appropriate patients, Ocrevus will be of great value in reducing the burden of MS." The treatment's approval, however, did not extend to — or mention — people with primary progressive MS, in contrast to the U.S. Food and Drug Administration's action in March, which approved Ocrevus for both MS forms. Health Canada did not give address PPMS in its announcement. Estimates are that 100,000 Canadians are currently living with MS, and most have the relapsing form. A number welcomed Ocrevus' arrival for what it offers in their fight against this disease.

The risk of people with multiple sclerosis developing cancer is higher if they have used immunosuppressants than if they haven’t, according to a study that followed more than 1,000 patients for a decade. The findings indicate that the often discussed association between MS and cancer may stem from older types of…

I was surprised to see that a study of a potential MS drug labeled MD1003 is still accepting participants. It’s a study that I’d love to take part in, if only I was a few years younger. MD1003 is a high dose of biotin, a form of…

A patient satisfaction evaluation of three autoinjector devices for delivering multiple sclerosis treatments found that Bayer’s electronic autoinjector Betaconnect was the choice of 57 percent of the 85 people who took part in the study. Higher satisfaction with an autoinjector can lead to better adherence, or patients sticking with treatment,…

Atara Biotherapeutics recently published an update of the company’s quarterly financial results and operational highlights, including the advancement of its T-cell based immunotherapy strategies for multiple sclerosis (MS) and cancer. One of the investigational therapies featured in the report is ATA188, a potential treatment for MS.

A bacteria present in the gut, called Prevotella histicola, prevented multiple sclerosis from developing in a preclinical mouse model, found researchers at the Mayo Clinic in Rochester, Minnesota, along with colleagues at the University of Iowa. Current research suggests that alterations to the gut microbiome residing in human intestines may potentially trigger inflammatory diseases such as MS. In an attempt to identify which gut resident bacteria are capable of modulating immune responses, researchers studied cultured small pieces of intestine tissue extracted from biopsies of patients with celiac disease. The team then isolated three bacteria strains and found that one of species — P. histicola — had the capacity to suppress MS in a preclinical animal model of the disease. “This is an early discovery but an avenue that bears further study," Dr. Joseph Murray, a Mayo Clinic gastroenterologist and the study's lead author, said in a press release. "If we can use the microbes already in the human body to treat human disease beyond the gut itself, we may be onto a new era of medicine. We are talking about bugs as drugs." By investigating how P. histicola modulated immune responses to suppress MS, researchers found that bacteria decreased the expression of two pro-inflammatory cytokines – interferon-gamma and interleukin (IL)-17. Overall results show that P. histicola has immune modulatory activity and can suppress abnormal immune responses, which ultimately prevent autoimmunity. This supports the idea that maintaining a healthy microbial community within our intestines is a potential therapeutic strategy for MS. "Our work is a classic example of a bedside-to-bench and potentially back to bedside study. Recent MS microbiome studies have shown the lack of Prevotella genus in patients with the disease and an increase when patients were treated with disease-modifying drugs," said Ashutosh Mangalam, the study's first author and an assistant professor of pathology at University of Iowa's Carver College of Medicine. "And it's not just for MS, because this may have a similar modulating effect on other nervous system and autoimmune diseases."

Insurance companies want people to use generics, rather than the more expensive brand-name drugs, right? Maybe not. Because, at least in some cases, they’re doing just the opposite. Some patients are being forced to use brand-name drugs even when those drugs have generic equivalents. Not surprisingly, that means…

Spasticity in multiple sclerosis patients can be eased through a combination of botulinum toxin type A (BoNT-A) injections and rehabilitation. However, caregiver support is required to keep patients on this treatment, according to results of a retrospective analysis. Spasticity, a muscle control disorder characterized by tight or stiff muscles, is a major MS symptom. The condition is significantly detrimental to patients’ quality of life, affecting their general mobility and balance. Several oral anti-spasticity drugs are available. However, “treatment of spasticity in MS is frequently challenging because of the complex clinical picture and the undesired effects associated with oral therapy, such as fatigue, dizziness, and hypotension,” the researchers wrote. Previous studies show that BoNT-A, a toxin that blocks nerve activity in muscles, is an effective therapy for the management of MS-related spasticity. The long-term effectiveness and persistence of BoNT-A use in patients with MS-related spasticity, however, remains poorly investigated. The research team in Italy proposed “to investigate the long-term persistence to treatment with BoNT-A for MS-related spasticity and the determinants of BoNT-A discontinuation in daily clinical setting.” In total, the researchers reviewed data from 185 patients, out of which 121 were considered in their final analysis. They observed that, at the end of the follow-up period, 44% of the patients in the analysis were still being treated with BoNT-A, but 56% had discontinued treatment. Overall, these results “confirm the beneficial effect of combining BoNT-A injections with rehabilitation and highlights the crucial role of caregivers for achieving better long-term outcomes in people with MS suffering from spasticity,” the team concluded.

Advancells says its stem cell-based therapy completely reversed multiple sclerosis (MS) in an Indian pilot trial with only one MS patient. The patient, Rahul Gupta, was diagnosed with MS seven years ago and has since suffered multiple relapses. His disease was progressing fast and he was quickly losing his ability…

TG Therapeutics and the U.S. Food and Drug Administration (FDA) have agreed on a special protocol assessment for a Phase 3 trial program evaluating TG-1101 (ublituximab) to potentially treat relapsing forms of multiple sclerosis (MS). A special protocol assessment (SPA) is a procedure by which the agency officially evaluates the…

I regularly see comments on various social media sites from MS patients who have traveled, or who plan to travel, outside the U.S. to be treated with stem cells. Some of these patients have reported excellent results and a reversal of symptoms. Others have died. Many MS patients…

Two compounds found in sunscreens suppressed multiple sclerosis symptoms in mice, a study shows. The substances, known as salate derivatives, belong to a class of compounds called nonsteroidal anti-inflammatory drugs. Evidence from the 1970s suggested that higher vitamin D levels from getting more sunlight could reduce the rate of MS. Subsequent studies indicated this was unlikely, however. Researchers who noticed that ultraviolet light suppresses MS in mice hypothesized that this could be the reason for the reduced prevalence of the disease in tropical areas. University of Wisconsin researchers wondered if sunscreen would prevent ultraviolet light from suppressing MS in mice. The team, led by Dr. Hector F. DeLuca, an emeritus professor in the university's Department of Biochemistry, chose six commercially available sunscreens, then exposed the mice to UV radiation. Confirming previous findings, they observed that UV radiation decreased the severity of MS. But, unexpectedly, they discovered that when mice were not receiving ultraviolet light, some of the sunblocks suppressed their MS for up to 30 days anyway. An analysis revealed that the salate derivatives homosalate and octisalate were the sunscreen components responsible for suppressing MS. The two are esters of salicylic acid, a common medication for acne, psoriasis, warts, and dandruff. Further analysis showed that homosalate was able to suppress MS by itself, but octisalate needed to be combined with homosalate to achieve significant results. The team also discovered that the salates' effectiveness depended on the dose. The more that homosalate was applied, the better the result, they said. The only adverse effect of homosalate and octisalate was temporary skin irritation. The study indicated that salate esters' ability to suppress MS is not due to their sunblocking ability per se, because some of the sunscreen brands that did a good job of blocking sunlight did not suppress the disease. Salate derivatives are well-known inhibitors of the enzyme cyclooxygenase, or COX. Because COX-2 has been found in MS lesions, salate derivatives might improve MS by suppressing COX, the researchers said. Overall, “salates may be useful in stopping the progression of MS, and may provide new insight into mechanisms of controlling autoimmune disease,” the researchers concluded.

Resistance training like weight lifting can protect or even regenerate the nerve cells of relapsing-remitting multiple sclerosis patients, slowing the progression of the disease, according to a clinical trial. A hallmark of MS is the brain shrinking faster than normal, and findings from this trial indicates that resistance training can slow the shrinking or even make some brain areas grow. Research has shown that physical training benefits MS patients, helping them alleviate many symptoms, including excessive fatigue and balance control problems. Recent studies suggest that exercise can have a disease-modifying role in MS. This means physical activity can be an important adjuvant, or add-on therapy, for standard-of-care regimens. Researchers followed 35 patients with relapsing-remitting MS for 24 weeks. Eighteen patients did resistance training twice a week, consisting of four lower- and two upper-body exercises. The other 17 patients struck with their normal routines. Before and after the 24 weeks, doctors took magnetic resonance imaging scans, or MRIs, to evaluate patients' brain structures. After the 24 weeks, the scans showed less brain shrinkage in those who had resistance training. Some of their cortical brain regions were also thicker — an indication they were growing. It is not clear why exercise benefits MS patients' brains, nor if exercise has the same effect on all patients. Additional studies are needed to clarify its therapeutic effect, the researchers said. That knowledge could help improve current MS therapies.

Twenty-four people have now received the multiple sclerosis and psoriasis therapy KY1005 in a Phase 1 clinical trial, according to its developer, Kymab. The Cambridge, England, company creates human antibody drugs for autoimmune diseases. The trial will focus on KY1005 as a psoriasis therapy, although its mechanism of action should work…

What does your neurologist consider when he or she is deciding how best to treat your multiple sclerosis? A recent report from Spherix Global Insights, a business intelligence and market research company that looks at drug trends every quarter, sheds some light on that. In my…

Long-term Tysabri (natalizumab) treatment of relapsing multiple sclerosis (RMS) improves physical and mental health and leads to greater satisfaction with therapy, new research shows. The study, ”Long-term natalizumab treatment is associated with sustained improvements in quality of life in patients with multiple sclerosis,” appeared in the journal…

Abarca Health has signed a value-based reimbursement contract with Biogen for select products in its multiple sclerosis (MS) portfolio. This is the first time such an agreement applies outcomes-based contracts to cover Medicaid patients in the United States. The deal offers a novel approach to connecting outcomes with the…

Ocvevus (ocrelizumab) is off to a running start, Tecfidera (dimethyl fumarate) leads the pills and the four injectable multiple sclerosis drugs are being used by fewer MS patients. But Copaxone (glatiramer acetate injection) remains the leader of the pack of the disease-modifying therapies. Those are…

Five clinics in the Washington area that specialize in administering intravenous and injected treatments to people with chronic diseases are now offering the new multiple sclerosis therapy Ocrevus (ocrelizumab). Arise Infusion Therapy Services said its staff is helping patients manage the authorization process that many insurers require before agreeing to cover…

A group of experts recently concluded that clinical trials are the best way to explore whether cell-based therapies are viable options for treating multiple sclerosis. In a newly published article, MS researchers reviewed evidence on a range of cell therapies, including stem cell transplants and delivery or stimulation of various cell types. Clinical trials, the panel argued, would be the optimal way to examine which types of cells should be used, how they should be delivered, and the types and disease stages the treatments are suitable for. The article focused on four types of cell-based treatments: autologous stem cell transplants, mesenchymal and related stem cell transplants, use of drugs to manipulate stem cells in the body to boost their ability to repair, and transplants of oligodendrocyte progenitor cells to trigger new myelin production. Loss of the myelin that protects neurons is a hallmark of MS. Such treatments hold promise to attain what current disease-modifying therapies in MS have not: halting the disease without lifelong treatment that has potential side effects, and regenerating damaged tissue. In addition to reviewing the evidence surrounding cell-based treatments, the expert group focused on the availability of the treatment options outside of controlled trials. “Media attention has resulted in some cases of misrepresentation and exaggeration of therapeutic claims for cell-based therapies for multiple sclerosis and other diseases,” the team wrote. This has caused patients to seek the treatments — paying out-of-pocket — at unregulated clinics. The panel noted that several drugs in development, including opicinumab, are aimed at promoting remyelination. In addition, drugs that are already approved for other conditions might have remyelinating properties, and might be repurposed to treat MS. Although studies are ongoing, the panel noted that it is unclear if the drugs do promote remyelination. Despite ongoing research and — in some cases — clinical use of cell-based therapies for MS, these treatments should be considered experimental, the expert group concluded. They again underscored the importance of clinical trials in providing a controlled environment for patients wishing to have cell therapy, as well as a source of evidence for the feasibility of these approaches.

Kezar Life Sciences announced that it is planning to move ahead with clinical testing of KZR-616, a potential treatment for multiple sclerosis (MS) and other autoimmune diseases and inflammatory disorders. The company recently concluded a Phase 1 safety study of the treatment, and raised $50 million in investment funding to support its development. KZR-616 is a first-in-class selective immunoproteasome inhibitor, meaning it works by blocking abnormal protein degradation. Cells eliminate proteins by sending them to a specialized cell compartment known as the proteasome. In immune cells, the proteasome is called immunoproteasome, and it regulates several selective inhibitors and participates in the regulation of the immune response associated with inflammatory diseases such as MS, rheumatoid arthritis, Crohn's disease, and lupus. "We are pleased with the results of our healthy volunteer study, and grateful for the support of such an excellent group of investors to finance our upcoming clinical trials," John Fowler, Kezar Life Sciences’ CEO, said in a news release. "The strong demand for this financing reflects growing excitement for the potential of immunoproteasome inhibition in treating autoimmune disorders and recognizes the clear leadership position enjoyed by Kezar." The Phase 1 trial enrolled 82 healthy subjects, who were assigned to receive either KZR-616 or placebo. In total, 61 volunteers were given KZR-616 as single or multiple doses at varying dose levels to identify the optimal dose for both tolerability and proteasome inhibition. Results will be presented at the American College of Rheumatology's Annual Meeting to be held in San Diego in November. "These initial clinical trial results demonstrate that KZR-616 is achieving the desired levels of immunoproteasome inhibition that correlate with anti-inflammatory activity seen in laboratory models,” said Christopher Kirk, PhD, company president and CSO. “By selectively targeting the immunoproteasome, we believe we can avoid the toxicities associated with dual proteasome inhibitors like Velcade and Kyprolis." The Series B financing round was led by Cormorant Asset Management and Morningside Venture and raised $50 million to support the development of KZR-616. Kezar announced it has the support of new investors, including Cowen Healthcare Investments, Pappas Ventures, Qiming Venture Partners, and Bay City Capital. "Cormorant is pleased to support Kezar as it enters an exciting series of patient studies, the first ever with a selective immunoproteasome inhibitor," said Bihua Chen, founder of Cormorant Asset Management. "While much work remains, I believe KZR-616 has the potential to be a transformative treatment in autoimmunity."

A cell therapy intended to boost myelin regeneration — Q-Cells by Q Therapeutics — has received a green light from the U.S. Food and Drug Administration to proceed with a clinical trial in patients with transverse myelitis (TM), a disease that like multiple sclerosis is characterized by myelin damage. FDA approval of the company’s Investigational New…

Eli Lilly and Nektar Therapeutics have established a development and commercial agreement for the investigational T-cell stimulator therapy NKTR-358 for the treatment of autoimmune disorders, including multiple sclerosis. NKTR-358, discovered and initially developed by Nektar, has the potential to modulate immune system responses to re-establish an immune balance in patients with autoimmune disorders. The treatment targets the interleukin 2 receptor complex (IL-2R) that is expressed on the surface of a subset of immune cells called regulatory T-cells, or Tregs. NKTR-358 activity stimulates the proliferation of Tregs, which in turn will regulate the activity of other immune cells that are uncontrolled and are responsible for the underlying mechanisms of autoimmune disorders. "We look forward to working with Nektar to study this novel approach to treating a number of autoimmune conditions," Thomas F. Bumol, PhD, senior vice president of biotechnology and immunology research at Eli Lilly, said in a press release. "NKTR-358 is an exciting addition to our immunology portfolio and reinforces Lilly's commitment to sustain a flow of innovative medicines in our pipeline." Bumol added. Under the agreement, Lilly and Nektar will continue to jointly develop NKTR-358. Nektar will be responsible for completing the ongoing Phase 1 clinical study; and Phase 2 clinical development costs will be shared by the two companies, with Lilly covering 75 percent of the costs and Nektar the remaining 25 percent. Nektar will have the option to take part of the Phase 3 development of NKTR-358 on an indication-by-indication basis. "We are very pleased to enter into this collaboration with Lilly as they have strong expertise in immunology and a successful track record in bringing novel therapies to market," said Howard W. Robin, president and CEO of Nektar. "Importantly, this agreement enables the broad development of NKTR-358 in multiple autoimmune conditions in order to achieve its full potential as a first-in-class resolution therapeutic." Based on the announced agreement, Lilly will pay an initial amount of $150 million to Nektar, which will also be eligible to receive up to $250 million from additional development and regulatory milestones. In the future, Nektar may also receive royalties from the product depending on its investment in NKTR-358’s Phase 3 development and future product sales. Lilly will cover all costs of global marketing of NKTR-358, and Nektar will have an option to co-promote the drug in the United States.

A new analysis of Phase 2 clinical data on Innate Immunotherapeutics’ investigational drug MIS416 to treat secondary progressive multiple sclerosis has confirmed that the drug failed to improve neuromuscular function or patient reported outcomes. The initial evaluation of data obtained from the one-year trial, announced in June, showed disappointing results. These results, gleaned from 70 patients who were randomly designated to receive either weekly injections of MIS416 or a placebo control, failed to demonstrate significant differences or clinically meaningful improvements in patients treated with MIS416 compared to those in the control group. After this initial setback, the Australian company sponsored an additional analysis of the trial results to identify any potential subgroup of clinical responders that could benefit from MIS416 and who might have been masked in the first population-based analysis. However, this post-hoc analysis also failed to show any positive effects of MIS416. Although the detailed report of this second analysis has not yet been released, the Sydney-based company conceded that the final outcome will not change. "All previous reports of MIS416 making a meaningful difference in the lives of many patients must either be dismissed as a very robust placebo effect or the trial failure is attributable to some other reason. It is my view that there may be other reasons," Innate CEO Simon Wilkinson said in a press release. "Patients with SPMS have a complex mix of symptoms and their disease can't be monitored by a simple blood test or MRI scan," he added. "We used the best assessment tools available as recommended by expert practitioners in MS, but we suspect they weren't sensitive enough to pick up the small but potentially significant changes that can lead to a substantial impact on patients' activities of daily living and quality of life." The lack of efficacy of MIS416 shown by the trial results is inconsistent with previous clinical experience, and the benefits reported by those receiving MIS416 for the past eight years.