March 31, 2017 | News |

FDA approves first treatment for primary-progressive MS

The U.S. Food and Drug Administration has approved the first medication to treat primary-progressive multiple sclerosis (PPMS), offering some hope to people with the rapidly disabling form of the disease. The drug will also be available to treat people with relapsing MS. The approval allows doctors in the U.S. to prescribe the drug; other countries, such as Canada, are expected to approve it over the next few months.

Ocrevus (ocrelizumab) is an infusion therapy (like Tysabri and Lemtrada) that is administered every six months. For the first course, two infusions are given two weeks apart; followed by one infusion every six months.

Unlike current MS medications, Ocrevus specifically targets one type of immune cell (B cells). (Other medications, such as Lemtrada, Gilenya and Aubagio, affect T cells and B cells.) Treatment results in a rapid reduction in inflammatory lesions in the brain, and a reduction in relapse rates. In two trials (called OPERA I and OPERA II) of people with relapsing MS, Ocrevus was significantly more effective than Rebif in reducing relapse rates (a 47% difference favouring Ocrevus), and MRI lesions (94% reduction vs. Rebif) (Hauser and colleagues. N Engl J Med 2017;376:221-234). A lower proportion of people experienced short-term worsening of their disability with Ocrevus compared to Rebif (9% vs. 14%). These results place Ocrevus in the higher-efficacy category, along with Tysabri, Gilenya and Lemtrada.

What makes Ocrevus unique is its effectiveness in progressive MS. About 10% of people with MS have the PPMS form at diagnosis; about 40,000 people have PPMS in North America. PPMS is characterized by few or no relapses, and a more rapidly disabling course. Since there is little inflammation, current MS medications, which primarily reduce inflammation, have not been effective in slowing disability. Numerous therapies have come up short in clinical studies, including Tysabri (ASCEND study), Gilenya (INFORMS study), Copaxone (PROMISE study), Rituxan (OLYMPUS study) and Betaseron (Spanish study).

The approval of Ocrevus for PPMS was based on a single study (called ORATORIO), which compared the drug with a placebo (Montalban et al. N Engl J Med 2017;376:209-220). Ocrevus had a significant effect on disability progression: 39% of people had worsening disability with Ocrevus compared to 55% with placebo. The difference was modest, but it was a landmark achievement to show that something could be done for people with PPMS.

It’s important to note that the people enrolled in the study were highly selected – they were younger (average age of 45 years), early in their disease course (within the first three years after diagnosis), had ongoing inflammatory activity, and generally did not have severe disability. So people who don’t match this profile may obtain less of a benefit.

The most common side effect is reactions at the time of infusion, which can include rash, skin itchiness and redness, tightening of the throat, difficulty breathing, dizziness, and heart palpitations. Your doctor will give you intravenous steroids and/or antihistamines prior to the infusion. The infusion takes about 2-3 hours, and a 1-hour observation period is needed after the infusion to monitor for infusion reactions.

Since Ocrevus affects the immune system, infections are also more common, notably virus infections (e.g. shingles, cold sores, genital herpes, etc.). So people need to be screened for hepatitis before taking Ocrevus, and should have all their vaccinations up-to-date beforehand. The product label also includes a warning that there may be an increased cancer risk, such as breast cancer. In the ORATORIO trial, the rate of malignancies was 2.3% with Ocrevus compared to 0.8% with placebo. The cancer risk is estimated to be about 1 case per year for every 200 people treated (Hauser 2017).

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