2. Ozanimod

Bristol-Myers Squibb
If approved, Bristol-Myers Squibb's ozanimod will be launching into a crowded multiple sclerosis market with several drugs using the same S1P-modulating mechanism. (Bristol-Myers Squibb)

Drug: ozanimod
Company: Bristol-Myers Squibb
Used for: multiple sclerosis
Est. 2024 sales: $1.598 billion

Ozanimod was a key component of Bristol-Myers Squibb’s $74 billion acquisition of Celgene. In fact, part of the payout to Celgene shareholders depends on FDA approvals for three pipeline drugs—including this multiple sclerosis candidate—by the end of 2020.

It was also partly responsible for Celgene’s sale at a relatively cheap price, after the FDA initially refused to even review the ozanimod application for approval, citing shortcomings in the pharmacology parts of the filing. That refusal-to-file news sent the company’s stock tumbling in early 2018.

Celgene refiled in March 2019, and now, as the new owner, Bristol-Myers is looking at a decision in relapsing forms of MS by March 25, 2020.

Management has high hopes for ozanimod, having pegged its peak sales to the tune of $5 billion. Among analysts polled by EvaluatePharma, the consensus for 2024 sales is more in the $1.6 billion range. But to break the blockbuster barrier at all, it’ll have to compete with several FDA-approved drugs, as well as promising experimental drugs.

Ozanimod is an S1P receptor modulator, designed to dampen inflammatory activity by preventing immune cells from exiting the lymph nodes into the central nervous system. Multiple existing blockbusters and blockbuster hopefuls are targeting the same mechanism. These include Novartis’ $3.3-billion-sales-per-year Gilenya, which is entangled in a patent fight and could face generics sooner than originally expected.

Celgene had touted ozanimod’s better safety profile than the older Novartis medication, particularly with regard to liver toxicities and heart side effects. But the MS up-and-comer has other, newer therapies to worry about.

Novartis also markets Mayzent, which, like ozanimod, selectively binds to S1P subtypes 1 and 5. Despite its own billion-dollar estimate, Mayzent only racked up $4 million in third-quarter sales. During a conference call in October, Novartis executives attributed the slow launch to a 90-day lag in getting patients through the reimbursement process. Such a setback could be a warning for MS greenhorn Bristol-Myers about the tough road ahead.

RELATED: Novartis, Merck KGaA and Biogen: Which new MS drug do doctors like best? You might be surprised

Also in the competitive oral MS field are Sanofi’s Aubagio, Biogen’s Tecfidera and its newly approved follow-up drug Vumerity—said to boast better gastrointestinal tolerability than its predecessor—and Merck KGaA’s Mavenclad. Besides, Johnson & Johnson’s S1P candidate ponesimod recently showed it could top Aubagio at lowering relapsing MS patients’ annual relapse rate in a phase 3 trial. And Mitsubishi Tanabe is developing another S1P agonist, amiselimod (MT-1303).

Injectables represent a rising force to be reckoned with, most notably Roche’s fast-growing antibody drug Ocrevus. Crowned as the most successful launch in Roche’s history, Ocrevus, administered only twice yearly, generated sales of CHF 2.66 billion in the first nine months of 2019, up 57% year over year.

Then there’s Novartis' repurposed leukemia drug Arzerra (ofatumumab). Yet unapproved in MS, it cut MS relapse rates by 50.5% and 58.5% respectively in two phase 3 studies when compared with Aubagio. A recent survey by SVB Leerink analysts showed that doctors really like this new Novartis drug. Physicians argue it offers “‘Ocrevus-like’ efficacy, with the convenience of self-administration” once every month, the analysts said.

However, all those drugs face a potentially damaging impact in the form of a patent challenge against market-leading Tecfidera from Mylan. The U.S. Patent and Trademark Office is scheduled to decide by early February whether Biogen’s argument for 2028 exclusivity is valid. If not, a cheaper copycat could enter as soon as this year, threatening not just Biogen’s $4.3 billion haul from the originator in 2018 but also the entire market.

On top of MS, Bristol-Myers is also gunning for ozanimod’s use in inflammatory bowel disease, where it’s in phase 3 testing.

2. Ozanimod