By Alex Keown
Since 2009 May 30 has been set aside as a day to raise awareness and campaign for an end to multiple sclerosis. The theme this year is focused on the research being conducted to develop a cure for the neurological disease.
The cause of multiple sclerosis (MS) is not known and there is no cure for the debilitating disease. It is estimated that about 2.3 million people globally live with the disease, with hundreds of thousands more who remain undiagnosed.
Across the pharmaceutical industry, companies are attempting to develop treatments for the disease. There has been some positive news from the clinic.
Most recently New Jersey-based Celgene said it was eying the first quarter of 2019 to submit a second New Drug Application (NDA) for multiple sclerosis treatment ozanimod. The announcement came after the U.S. Food and Drug Administration (FDA) issued a Refusal to File letter in February regarding some insufficient data. In April though, the company met with the FDA to seek guidance and then announced its intentions in May. Celgene expressed confidence in the efficacy of ozanimod and its path to approval next year. The one year delay is due to the FDA’s request for non-clinical bridging studies. The NDA was based on positive Phase III results that showed ozanimod demonstrated superiority versus Biogen’s Avonex (interferon beta-1a) in reducing annualized relapse rates and MRI brain lesions.
In April Genentech, a subsidiary of Roche, presented data at the American Academy of Neurology meeting in Los Angeles that showed that Ocrevus, a monoclonal antibody designed to target CD20-positive B cells, slowed disability progression in MS and supported the approach of early disease treatment. Patients who were on the treatment for four years saw a sustained reduction in underlying disease activity, Genentech said. Additional analyses show Ocrevus delayed cognitive decline and improved cognitive function in RMS, as measured by Symbol Digit Modalities Test. Additionally, Treatment with Ocrevus also provided greater disease relief to patients who had been taking interferon beta-1a therapies. Data showed that patients who remained on the drug during the study maintained low numbers of T1 gadolinium-enhancing (T1Gd+) lesions at year four.
In March Novartis made multiple moves in the MS sphere. On March 1 the company forged a collaborative deal with Pear Therapeutics to develop prescription digital therapeutics for schizophrenia and multiple sclerosis. Just a few weeks later the Swiss pharma giant announced it planned to seek approval from the FDA for siponimod in secondary progressive multiple sclerosis (SPMS). Data released by Novartis in late March showed the medication had a “21 percent decrease in the risk of disease progression, reduced the brain volume loss rate by 23 percent, limited T2 lesion volume from increasing by a mean of about 80 percent, cut the annual relapse rate by 55 percent, and showed reduced disease progression to about 26 percent at six months,” BioSpace reported at the time. The one setback for the Novartis medication was that it did not significantly improve walking performance in patients. However, data from a post-hoc analysis published one month later showed that siponimod-dosed patients gained a significant benefit in cognitive processing speed. That speed is the key cognitive function impacted by multiple sclerosis, the Swiss-based company said.
Based on the results from that late-stage trial, Novartis intends to seek FDA approval, as well as approval in Europe.
A new MS drug is key for Novartis as it seeks to protect losses from its $3 billion per year generating MS drug Gilenya. Analysts predict significant revenue losses within the next two years due to generic competition. In addition to Gilenya Novartis also markets Extravia as a treatment for relapsing forms of the disease.
Where there is progress there is also setback. In March Biogen and AbbVie announced they were pulling Zynbrita for relapsing multiple sclerosis (MS) off the market following reports of safety concerns. In Europe there were reports of inflammatory encephalitis and meningoencephalitis in patients taking the drug. In their announcement about the decision to pull Zynbrita, Biogen and AbbVie said that due to the “nature and complexity of adverse events being reported,” that it would be impossible, considering the number of patients being treated, to continue. In the United States Zynbrita was approved as a third-line treatment by the FDA in 2016 with a black box warning regarding the possibility of liver toxicity.
Although Biogen experienced a setback with Zynbrita, in April the company said it expects to see progress in its pipeline, including expected milestones in multiple sclerosis therapies. Biogen anticipates taking an asset it acquired from Alkermes plc last year and filing for approval with the FDA. Biogen anticipates head-to-head data from BIIB098 in comparison with its own MS drug, Tecfidera.
But as the pharma industry attempts to develop treatments, and one day hopefully a cure for MS, patients and advocates will join together in the #bringinguscloser campaign to celebrate milestones in the fight against the disease and express hope for the future.