Barely a day after its PDUFA date, despite the unfolding COVID-19 pandemic, the FDA has approved Bristol Myers Squibb Co.'s immunomodulator, ozanimod, an oral treatment for adults with relapsing-remitting multiple sclerosis (MS) and active secondary progressive disease branded as Zeposia. The win, a much-anticipated milestone precipitated by the company’s multibillion-dollar acquisition of ozanimod developer Celgene Corp. in November 2019, gives patients a new treatment option amid a growing field of therapies for MS.
BMS said March 26 that, with the country’s health care system busy dealing with the unprecedented pandemic, it will delay commercialization of Zeposia as it continues to "monitor the environment." Final pricing is on hold until launch. An EMA decision on the MAA for the drug is expected by midyear.
“MS affects each person in a unique way, and response to disease-modifying therapies may vary,” said Kathy Costello, associate vice president of health care access at the National MS Society. "Having access to multiple treatment options is important, so the approval of oral Zeposia is a welcome addition for people with relapsing forms of MS. We hope that the marketing delay will be of short duration."
With no requirements for first-dose cardiac monitoring or ophthalmic assessment, RBC Capital Markets analyst Brian Abrahams called the label "clean." And, in a note sizing up Zeposia's prospects vs. Biogen Inc.'s MS franchise on Thursday, he said it sets the stage "for it to be an important additional entrant in the MS space – one we note is becoming increasingly crowded."
Zeposia will primarily compete with Novartis AG's Gilenya (fingolimod), Sanofi SA's Aubagio (teriflunomide) and Biogen's Tecfidera (dimethyl fumarate). Sales of the new drug, if analyst expectations are met, could reach $1.493 billion by 2024, according to a recent Cortellis analysis.
The FDA green light marks a full reversal of fortune for Zeposia, which faced a refuse to-file-letter in February 2018, when the FDA sought additional information before agreeing to further assess the original NDA.
A therapy for the majority
With MS, a patient’s immune system attacks the myelin sheath that surrounds neuronal axons, disturbing motor and sensory functions, with damage that can lead to paralysis and cognitive dysfunction. It affects about 2.5 million people worldwide, according to the U.K.-based Multiple Sclerosis Trust.
Neurologists diagnose MS patients as having one of three types. About 85% fall into the relapsing-remitting form of MS, while 15% have primary progressive disease. More than half of those with relapsing MS later become secondary progressive MS (SPMS) patients.
Zeposia, an oral agonist of the sphingosine 1-phosphatase (S1P) 1 and 5 receptors, was invented at La Jolla, Calif.-based Scripps Research by professors Hugh Rosen, Edward Roberts and their laboratory colleagues. As described by Scripps, “it works by acting on certain types of immune cells called lymphocytes that are centrally involved in the autoimmune attack on myelin sheath. It binds to receptors on the cells’ surface, keeping them from reaching the brain. As a result, the number of activated lymphocytes is decreased, diminishing the immune attack.”
The NDA and MAA filings for the medicine were based on phase III data from the Sunbeam and Radiance trials, both of which met the primary endpoints, showing the annualized relapse rate (ARR) at 12 months was 0.18 with Zeposia vs. 0.35 with Avonex (interferon beta 1a, Biogen Inc.) and the ARR at 24 months was 0.17 vs. 0.28, respectively.
Safety data showed similar cardiac events to placebo, which may differentiate ozanimod from the first S1P therapy and oral disease-modifying agent approved in 2010, Gilenya. The second approved in March 2019, also from Novartis, was Mayzent (siponimod). Cardiovascular risk observed in some patients became a hurdle for Gilenya. Mayzent gained approval for relapsing MS, but it also became the first therapy approved for the SPMS population. It was soon followed in April 2019 with another relapsing MS and SPMS treatment, Mavenclad (cladribine, Merck KGaA), a synthetic chlorinated deoxyadenosine analogue.
When launch day does eventually arrive, prescribing will no doubt be helped by the drug escaping requirements for a series of tests needed for other drugs in its class, such as Gilenya and Mayzent. Gilenya requires electrocardiogram tests prior to and for six hours following the first dose to monitor for signs of arrhythmia. Both Mayzent and Gilenya require ophthalmology evaluations and blood work.
One step closer
Zeposia's approval clears the first of three hurdles needing to be leapt before contingent value rights (CVRs) held by former Celgene shareholders pay out. When BMS officially closed its acquisition of Celgene for total consideration of $80.269 billion, Celgene shareholders received one BMS share and $50 in cash for each share of Celgene along with one tradeable CVR per share, valued at $9. Now just two other milestones need to be met – regulatory approvals of lisocabtagene maraleucel by Dec. 31 and idecabtagene vicleucel by March 31, 2021 – for the CVRs' value to be realized.
Shares of BMS (NYSE:BMY) climbed 5.9% Thursday, closing at $52.25 per share. Trading in the CVRs (NYSE:BMY-R), which trebled in high volume trading, drove their value up to $3.02, or about a third of their potential final value.