After 40 years of clinical trials, the Food and Drug Administration (FDA) has finally approved a new drug, ocrelizumab, which will treat primary progressive multiple sclerosis (MS) based on Dr Stephen Hauser’s research.

“I think if the safety holds up, it will become the leading MS therapy,” said Dr Steven L Galetta, the chairman of the department of neurology at NYU Langone Medical Center.

Novel drug target provides hope for MS patients

With an estimated 400,000 people suffering from MS in the US and approximately 15% with the primary progressive form of the disease, ocrelizumab is offering hope to patients who have no options to battle against this disease, and would otherwise result in paralysis and cognitive decline.

“It’s personally incredibly rewarding,” said Hauser, director of the Weill Institute for Neurosciences at the University of California and lead researcher of the study. “This is a big deal for people with MS.”

“This is a major therapeutic advance. And it opens a whole new area of understanding about MS,” remarked Dr Harold L Weiner, director of the Partners MS Center at Brigham and Women’s Hospital in Boston.

Unlike other MS drugs in the market that target the immune system’s T cells, the drug takes a different approach by blocking B cells, which have similar roles in the immune system. It took Hauser and his lab a decade to identify B cells and their related antibodies as promising new drug targets, as the scientific establishment had initially rejected the idea.

He added, “The magnitude of the benefits that we’ve seen with ocrelizumab in all forms of MS are really quite stunning.”

On the other hand, the drug is estimated at a list price of USD $65,000 a year, which is 25% less than an existing disease-modifying drug, although it is four times more expensive than 12 years ago.

Initial struggles led to success in phase III trial

In 1997, his group worked together for the first treatment directed against B cells using a genetically engineered antibody called rituximab, with FDA’s approval.

However, Hauser and his colleagues met with several hurdles concerning the rate of chances of success until Genentech, a biotechnology company, agreed to a trial in 2003 with the support of a few top insiders who supported the idea.

Dr Stephen Hauser is the lead researcher for the multiple sclerosis drug trial. Photo credit: Elizabeth D Herman/Stat
Dr Stephen Hauser is the lead researcher for the multiple sclerosis drug trial. Photo credit: Elizabeth D Herman/Stat

“We were hoping to see a tiny whiff of effect to lead to other clinical trials,” Hauser said. The researchers conducted a placebo-controlled trial based on FDA’s required standards, and obtaining satisfying results led them to the invention of ocrelizumab.

As rituximab was an ageing medicine with safety issues, Genentech proposed a molecule that was better suited for MS, which was ocrelizumab.

“We recognised this was a very important finding in MS. It provided the first clinical evidence that B cells really were important in the disease,” Dr Peter Chin, group medical director for neuroscience at Genentech, said of the pilot study’s data.

Hence, a larger phase III trial launched in 2011 has led to FDA approval with unprecedentedly remarkable results.

Important first step despite drawbacks

Although it is not a cure and the results are considered modest, medical experts describe ocrelizumab as an important first step.

The drug has shown to halt progression of the disease with relatively safe side effects. The side effects documented include reactions at the injection site where the drug is administered every six months, more upper respiratory infections and core sores.

Nonetheless, there are studies that raised the possibility of a slightly heightened risk of cancer with the drug. Doctors are therefore advised to follow up with the use of the drug as research continues.

If the initial efficacy and safety of the drug can be maintained over a period of use and observation, Hauser is confident that newly diagnosed MS patients can “look forward to a full life without significant disability.”

“Ocrelizumab’s success has led to a rethinking of how the other MS therapies may be working.” MIMS

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