New MS treatment now available
Ponvory (ponesimod) is the latest MS treatment approved by Health Canada, providing another option for people with multiple sclerosis. The drug is the fourth in a class of so-called S1PR therapies, which includes Gilenya, Zeposia and Mayzent. All of these medications prevent a type of immune cell (called T cells) from entering the brain and causing inflammation and damage. Ponvory is the most selective of the S1PR drugs, although it is unclear if this selectivity offers any advantages.
The first drug in this class, Gilenya, was approved in 2010. A limitation was that it can cause heart rhythm abnormalities so it needed to be started under medical supervision at a first-dose clinic. Effects on the heart can be minimized by starting with a low dose, then slowly increasing until an effective dose is reached. This has been the strategy with subsequent S1PR drugs, eliminating the need for first-dose supervision except for people with pre-existing heart conditions.
The dosing schedule for Ponvory is complicated, requiring 10 different doses over a 15-day period. The starting dose is 2 milligrams, increased in 1-mg increments every other day, then doubled to the therapeutic dose of 20 mg on day 15. This schedule will be longer if any doses are skipped; if you miss 4 days in a row, you’ll need to start all over again.
The efficacy of Ponvory was shown in the phase III OPTIMUM trial against Aubagio (Kappos and colleagues. JAMA Neurol 2021;78:1-10). That study found that Ponvory was superior to Aubagio in reducing the frequency of relapses and inflammatory lesions in the brain. However, the relapse advantage was small, and Ponvory was no better than Aubagio in slowing the worsening disability that occurs in MS. (Zeposia had the same problem in its clinical trial, failing to show that it was superior to Avonex in slowing disability.) Fatigue scores were reportedly better with Ponvory compared to Aubagio, although the FDA found that these differences were not meaningful (FDA Summary Review, 18 March 2021).
The most common side effects with Ponvory include elevated liver enzymes (detected with a blood test), headache, upper respiratory infection and high blood pressure. Other side effects seen with this class of drugs include slowing of the heart rate, increased blood pressure, and infections. Side effects are usually mild, treatable or reversible if the drug is stopped. The frequency of side effects was similar for Ponvory and Aubagio, although more people taking Ponvory in the trial stopped treatment because of side effects.
A number of procedures will be needed before starting Ponvory, such as a blood test (to check blood cells and liver function), an electrocardiogram (ECG), and an eye examination. People who have not had chickenpox will need to be vaccinated; vaccination against human papillomavirus (HPV) should be considered. Women in their childbearing years will need a test to ensure they are not pregnant and will need to use contraception while on Ponvory. It is important to use a sunblock and avoid tanning booths during treatment due to a risk of skin cancers. The FDA raised a concern about possible euphoria with Ponvory (with a risk of abuse); the reasons for this are not immediately clear and this issue will require further study.
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