Ponvory (ponesimod), an approved oral therapy, is used to lower relapse rates and slow the development of brain lesions in people with relapsing forms of multiple sclerosis (MS).
It was originally developed by Actelion, which is now part of Janssen.
Ponvory is a selective modulator of a group of receptors called the sphingosine 1-phosphate (S1P) receptors. These receptors control immune cell migration from lymph nodes — organs where some immune cells are matured and stored — to the blood.
By modulating S1P receptors, Ponvory is believed to “trap” immune cells in lymph nodes, preventing them from getting into the nervous system and causing the inflammation that drives MS. The therapy induces a rapid, dose-dependent reduction in immune cell numbers in circulation. This effect is reversible, wearing off within one or two weeks after treatment discontinuation.
S1P receptors also are found on some cells in the brain and spinal cord. Studies in animal models suggest that Ponvory is able to cross the semi-permeable membrane that protects the brain from immune cells and large molecules circulating in the brain, and exert neuroprotective effects on these cells of the nervous system.
The U.S. Food and Drug Administration approved Ponvory in 2021 for adults with relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting MS (RRMS), and active secondary progressive MS (SPMS).
The European Commission approved the therapy for use in the EU in the same year, for adults with relapsing forms of MS and active disease, as defined by certain clinical or imaging features.
Ponvory should not be given to people who have experienced serious heart problems, such as heart attack, chest pain (unstable angina), stroke or mini-stroke, or certain types of heart failure, in the past six months.
Individuals with certain types of heart block or abnormal heart rhythms (arrhythmia) also should not take Ponvory unless they have a functioning pacemaker device.
Ponvory is available in round, film-coated tablets that come in 10 different strengths. The recommended dose is 20 mg once daily. This dose is available as a yellow tablet with a “20” engraved on one side and an “A” on the other.
However, patients starting on the medication, or restarting it after missing four or more consecutive doses, will receive a two-week starter pack to gradually increase the dosage from 2 mg to the maintenance dose of 20 mg. This dose titration pack includes:
Ponvory may be taken with or without food, and tablets must be swallowed whole.
Because initiation of Ponvory treatment may cause a decrease in heart rate, it is recommended that patients with certain heart conditions are monitored for at least four hours after taking the first dose of this medication.
Actelion funded a Phase 2 study (NCT01006265) that tested different doses of Ponvory — 10 mg, 20 mg, and 40 mg — against a placebo in 464 RRMS patients over 24 weeks.
Findings from the trial showed that the 20 mg dose significantly reduced the number of new inflammatory brain lesions visible on MRI scans, by 83%, compared with a placebo. It also significantly lowered the number of new or enlarging brain lesions (by 56%) and reduced the risk of a first confirmed relapse (by 21%).
Most participants from this trial, which was completed in 2011, entered a worldwide extension study (NCT01093326) that is monitoring relapse rates, disability progression, and adverse events for up to 660 weeks (about 12.5 years). The extension study is expected to finish in October 2023.
Ponvory’s approval was supported by data from the OPTIMUM Phase 3 trial (NCT02425644), completed in 2019. It compared the 20 mg dose of Ponvory with Aubagio (teriflunomide), an approved oral MS therapy. The study enrolled 1,133 adults with RRMS or active SPMS and ran for 108 weeks, or about two years.
In this trial, Ponvory significantly lowered relapse rates compared with Aubagio. Specifically the difference was 0.202 versus 0.290 relapses per year — a 30.5% relative reduction. Ponvory also outperformed Aubagio in controlling fatigue, and reduced the number of new disease lesions on MRI scans by 56%.
The two medications, however, did not differ in terms of the proportion of patients with confirmed disability progression; it generally was low with both treatments. Further data from the trial indicated that the benefits of Ponvory were more pronounced in patients who started the treatment early on in the course of their disease.
A long-term extension of OPTIMUM (NCT03232073) is now underway with 871 participants, all of whom are receiving the 20 mg dose of Ponvory for about seven more years. The primary goal is to explore the treatment’s long-term safety and efficacy, but investigators also will examine the safety of switching to Ponvory among participants who received Aubagio in the initial OPTIMUM trial.
A COVID-19 vaccination study also will be performed among a subset of up to 50 participants. This study will assess the effects of receiving the Janssen COVID-19 vaccine during treatment with Ponvory.
The OPTIMUM extension trial is expected to be completed by February 2024.
Data show that the most common side effects associated with Ponvory in clinical trials are:
Ponvory lowers the levels of immune cells in the blood, which can raise the risk of infections. Monitoring for infections is recommended for patients taking the medication, and treatment should be delayed for anyone with active infections.
Patients on Ponvory should not receive vaccines containing a live virus. Those who have no history of chickenpox or records of receiving a vaccine for chickenpox are recommended to receive a full course of vaccination against the varicella zoster virus. That should be completed at least one month prior to beginning the therapy.
Starting Ponvory may cause a temporary decrease in heart rate, and some patients can experience increases in blood pressure. Heart health should be thoroughly assessed before starting the therapy, and blood pressure should be monitored during treatment.
Because Ponvory may cause shortness of breath, the medication should be used with caution in anyone with severe respiratory diseases. Lung function should be assessed during treatment if clinically indicated.
Ponvory may cause injury to the liver and is not recommended for patients with moderate or severe liver impairment. Liver function should be assessed before starting on the medication, and treatment should be stopped if significant liver injury is confirmed.
The risk of skin cancers, such as basal cell carcinoma, melanoma, and squamous cell carcinoma, may be increased with Ponvory treatment. Patients should undergo regular skin examinations, and are advised to follow usual guidelines for people at high risk of skin cancer, particularly using sunscreen or wearing clothing that protects from sunlight exposure. Any suspicious lesions should be promptly evaluated.
A form of swelling in the eye called macular edema has been reported in some patients. It is especially common in people with diabetes or a form of eye inflammation called uveitis. An ophthalmic evaluation is recommended for all patients before starting on Ponvory, and at any time a change in vision is reported.
A condition called posterior reversible encephalopathy (PRES), which is caused by swelling and narrowing of blood vessels in the brain, has been reported in patients taking other S1P modulators. Patients should contact their healthcare provider immediately if they experience PRES symptoms, including sudden, severe headache, confusion, vision changes, or seizures.
The effects of Ponvory in pregnant women are unknown, but animal studies suggest that the medication may cause damage to a developing fetus. People who can become pregnant should use an effective method of contraception during and for one week after stopping treatment.
Research in animal models also has found evidence that Ponvory can pass into breast milk. Patients should talk with their healthcare provider if they plan to breastfeed while on the medication.
Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
Ponvory was approved by the U.S. Food and Drug Administration in March 2021 for adults with relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting multiple sclerosis, and active secondary progressive multiple sclerosis.
Animal studies suggest that Ponvory may cause harm to a developing fetus. People with the potential to become pregnant should use contraception methods while on Ponvory and for one week after stopping treatment.
No interactions between Ponvory and alcohol have been reported. But patients should discuss with their healthcare provider whether it is safe to drink alcohol while on Ponvory, since alcohol can sometimes interfere with disease symptoms and medications.
Some patients may begin seeing results as early as six months after beginning treatment. In a Phase 2 trial involving more than 450 people with relapsing-remitting multiple sclerosis, those who received the recommended dose of Ponvory had a significant reduction in new inflammatory lesions after six months, compared with patients receiving a placebo. However, multiple sclerosis manifests very differently among patients, and people’s responses to treatment also vary. Patients should talk with their healthcare team to understand how the medication might help in their specific case.
Weight gain has not been reported in clinical trials as a side effect associated with Ponvory. Hair loss (alopecia), however, was reported by a small percentage of patients in the OPTIMUM Phase 3 trial. Patients are advised to discuss with their healthcare provider if they experience these problems.
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