Written by Susan Courtney and Tom Garry
Reviewed by Dr. Barry A. Hendin, MSAA Chief Medical Officer
FDA Approves Ponvory™ for the Treatment of Relapsing Forms of MS
On March 19, 2021, the Janssen Pharmaceutical Companies of Johnson & Johnson announced that the United States Food and Drug Administration (FDA) approved Ponvory™ (ponesimod) for the treatment of relapsing forms of multiple sclerosis (MS) in adults – including clinically isolated syndrome, relapsing-remitting, and active secondary-progressive forms of MS. This new disease-modifying therapy (DMT) is taken orally (by mouth) once daily and has been shown to reduce annual relapse rates and reduce disease activity as shown on magnetic resonance imaging (MRI), compared to treatment with an approved DMT, Aubagio® (teriflunomide). Ponvory should be available by prescription in April 2021.
In addition to its proven efficacy, Ponvory is well-tolerated and provides some additional benefits, such as its quick rate of leaving the blood system should the medication need to be stopped. The most common side effects include upper respiratory tract infections, elevated liver enzymes, and high blood pressure. Those with certain heart conditions, or women who are planning to be or are currently pregnant, should not take Ponvory.
Study Findings and How Ponvory Works
The approval of Ponvory was partly based on a two-year, head-to-head Phase III clinical trial, where the efficacy, safety, and tolerability of Ponvory (20 mg taken orally, once per day) was compared to Aubagio® (teriflunomide), which was taken in oral doses of 14 mg once daily. Referred to as the OPTIMUM trial (Oral Ponesimod Versus Teriflunomide in Relapsing Multiple Sclerosis), this study included 1,133 participants and found the following results for treatment with Ponvory when compared to Aubagio:
- 30.5% lower annual relapse rate
- 71% of participants had no confirmed relapses, compared to 61% in the Aubagio group
- The number of new gadolinium-enhancing (GdE) T1 lesions and the number of new or enlarging T2 lesions were reduced by 59% and 56% respectively
- Worsening disability was prevented for most people, although the differences in rates between the two medications were not significant
Ponvory is a selective sphingosine-1-phosphate receptor (S1P) modulator that is believed to work by keeping immune cells called lymphocytes out of the blood by trapping them in the lymph nodes. Lymphocytes that circulate in the blood and cross the blood-brain barrier to enter the central nervous system are thought to cause the damage to nerves seen in MS. Other approved sphingosine-1-phosphate (S1P) receptor modulators for MS include Gilenya® (fingolimod), Mayzent® (siponimod), and Zeposia® (ozanimod).
Should this medication need to be stopped at any time, it leaves the blood within one week, and the effects on the immune system wear off in one to two weeks for most patients. This is of benefit for people who may be waiting to get a vaccine, who plan to become pregnant, or who need to stop the medication for any other reason.
According to Johnson & Johnson, “Ponvory does not require genetic testing or first-dose cardiac monitoring for most patients. Because initiation of Ponvory treatment results in a decrease in heart rate, first-dose monitoring is recommended in patients with certain preexisting cardiac conditions.”
Side Effects and Adverse Events
As noted earlier, the most common side effects include upper respiratory tract infections, elevated liver enzymes, and high blood pressure. Adverse effects can include more serious infections and a slowed heart rate (bradycardia or bradyarrhythmia) when starting Ponvory. To help minimize the potential for initial side effects, patients begin taking Ponvory in a titrated “starter pack” for the first 14 days. The starter pack begins with a low dose and gradually increases to the full dose approved by the FDA.
Ponvory lowers the number of white blood cells (lymphocytes) in the blood. This medication also increases the risk of infection, including serious infection that can be life-threatening. To monitor the risk, individuals should have a recent blood test prior to starting the medication, and while taking the medication, should watch for signs of infection, such as fever, body aches, nausea, and headache, among others.
Since Ponvory can affect the heart rate, individuals need an electrocardiogram (ECG) to check the electrical activity of their heart before taking the first dose. People with certain cardiac conditions, such as those who have had a heart attack or stroke, or those experiencing angina, heart failure, or abnormal heartbeat, should not take Ponvory. Those pregnant or planning to become pregnant, or who are breastfeeding, should not take Ponvory. Individuals are advised to tell their doctor about any health condition prior to starting this medication.
For More Information
The maker of Ponvory has two programs available to the MS community. The first is Janssen CarePath, which offers support and information on insurance coverage, potential costs, and options for making treatment more affordable. The second is the Wellness Companion Program, which provides one-on-one education to help patients get started and continue treatment. For more information, please visit www.ponvory.com, or call a Janssen CarePath Care Coordinator at 877-CarePath (877-227-3728), Monday-Friday, 8:00 AM to 8:00 PM ET.
Plegridy® Now Approved for Intramuscular Injection
In February 2021, the United States Food and Drug Administration (FDA) approved a new intramuscular injection route of administration for Plegridy® (peginterferon beta-1a), a disease-modifying therapy (DMT) for relapsing forms of MS. The medication is marketed by Biogen, a Cambridge, MA-based biotechnology company.
The FDA first approved use of the interferon-based DMT in 2014. Since then, the medication has been administered subcutaneously, meaning that a short needle is used to inject the DMT into the tissue layer between the skin and the muscle.
Maha Radhakrishnan, MD, Biogen’s chief medical officer, says the newly approved intramuscular route of administration “gives new and current MS patients a different delivery method that has the potential to significantly reduce injection-site reactions.”
Biogen noted that the FDA’s approval of the intramuscular (IM) administration of Plegridy is based on data evaluating bioequivalence and adverse reactions associated with IM administration compared to subcutaneous (SC) administration in healthy volunteers. Bioequivalence between the two dosing regimens was confirmed, and data showed that participants receiving Plegridy through IM administration experienced fewer injection-site reactions than participants receiving SC administration (14.4% vs. 32.1%).
Assessing Ocrevus® in Older Adults with Progressive MS
The impact of disease-modifying therapies (DMTs) on MS often is easier to evaluate in younger adults than older people. This owes in part to the fact that younger people tend to have more inflammatory disease activity, providing a clearer baseline against which to measure the effect of a medication. Similarly, older people are less likely to have relapses, diminishing the utility of measuring changes in annual relapse rate as a marker of medication efficacy. Further, older people are likely to have more comorbid conditions – such as osteoarthritis or diabetes – making it difficult to determine whether impaired mobility, fatigue, or another symptom is due to MS or some other cause.
To better understand the impact of the DMT Ocrevus® (ocrelizumab) in older people with multiple sclerosis, researchers recently analyzed data on people with progressive forms of MS who were age 56 years and older.
Ocrevus is an anti-CD20 therapy, meaning that it exercises its effects on the CD20 molecule found on the surface of the immune system’s B cells. These cells are believed to play a role in the development of MS. Ocrevus is approved by the FDA to treat both relapsing and progressive forms of MS. Clinicians also sometimes use another anti-CD20 therapy, rituximab, to treat MS. However, rituximab is not approved for use in MS, although the FDA has approved its use for a number of other diseases.
The researchers focused primarily on 24 patients for whom they had data for two years before those people began either Ocrevus or rituximab and for two years after they started taking Ocrevus. Seventy percent of those people had been on another type of DMT before beginning anti-CD20 therapy.
After analyzing their results, the investigators reported, “We found no difference in two-year clinical endpoints for patients while on ocrelizumab [Ocrevus] compared to prior to [starting] anti-CD20 therapy, though there was a trend toward decreased CDP [confirmed disability progression] on ocrelizumab that our study was not sufficiently powered to analyze.”
While the investigators noted that larger studies are needed to examine this issue, the fact that progressive MS patients’ clinical status did not worsen over roughly four years – including the last two on Ocrevus – is encouraging.
For More Information
For general information or to speak with a trained Client Services Specialist, please call MSAA’s Helpline at (800) 532-7667, extension 154. Helpline hours are Monday through Thursday, 8:30 AM to 8:00 PM, Eastern Time; and Friday 8:30 AM to 5:00 PM Eastern Time. Questions to MSAA’s Client Services department may also be emailed to MSquestions@mymsaa.org