Celgene Plots Blockbuster Course For Ozanimod

Celgene, in need of good news, posted positive data on a potential blockbuster for multiple sclerosis at the joint ECTRIMS-ACTRIMS meeting. Ozanimod could have important safety and tolerability advantages over Gilenya, but investors already were expecting good news.

Celgene Corp. is ramping up for commercialization of ozanimod in multiple sclerosis, although a potential launch is at least a year out. Inflammation & Immunology President Terrie Curran said the company already is expanding marketing, patient services and field sales as it preps to move into a new therapeutic area, during a presentation at the joint ECTRIMS-ACTRIMS meeting in Paris Oct. 28.

The company released detailed results from two Phase III trials, RADIANCE and SUNBEAM, testing ozanimod in patients with MS during the meeting, including good safety data that could be an important differentiator for the drug in a crowded category. The two trials enrolled 2,666 patients combined.

Celgene previously released top-line data from the trials, demonstrating positive efficacy versus an active comparator, Biogen Inc.'s Avonex (interferon beta-1a). (Also see "Celgene's Positive Ozanimod Data Puts Focus On MS Commercialization" - Scrip, 22 May, 2017.) At the time, Celgene said it planned to file a new drug application (NDA) for US FDA approval of ozanimod by the end of the year.

No safety data were previously released, however, and those results are important because ozanimod is a selective sphingosine 1-phosphate 1 (SIP1) and 5 receptor modulator that will have to compete against Novartis AG's SIP1 modulator Gilenya (fingolimod).

Gilenya has some serious adverse events, including a decrease in heart rate upon initiation that requires monitoring on top of increased blood pressure, liver damage and increased risk of infections, among other warnings. Celgene believes ozanimod has superior safety and tolerability, because it is more selective, which will position the drug as best in its class. That could be particularly important when generic competition for Gilenya hits the market as expected in 2019.

"We really are seeing some emerging themes that would potentially enable us to be … the leading oral compound on the market," Curran said.

Building A Specialized Commercial Group

Celgene expects ozanimod would be used as a first-line option for patients with multiple sclerosis, or as a first switch from another therapy, she said.

Initially, Celgene talked about possibly seeking a partner to market ozanimod for multiple sclerosis, while commercializing the drug on its own in ulcerative colitis, after acquiring it in the $7.2bn purchase of Receptos Inc. in 2015. (Also see "Celgene Sets Sights On Becoming Inflammation and Immunology Power Player" - Pink Sheet, 20 Jul, 2015.) But more recently, management has talked about multiple sclerosis as a good fit for Celgene.

"This is a highly concentrated market in terms of the prescriber base," Curran said. "Eighty percent of the business is driven in the US by around 3,000 prescribers, so this is a really important consideration when we're thinking about entering a new market. It's a market that is highly specialized, which really fits with Celgene's capabilities."

Like hematology, where Celgene has long been a leader, multiple sclerosis is a "high-touch" category, she said. In that regard, the company is focused on building outpatient services to assist patients, and is developing expertise in reimbursement.

"We're finalizing the field footprint and structure and accelerating brand activities, and … really developing that kind of wraparound patient services that we know we'll need to really have to compete in this category," she added.

Investor Expectations Met

The news out of the ECTRIMS-ACTRIMS meeting was a much-needed positive for Celgene, which is counting on Inflammation & Immunology to offset its dependence on the blood cancer drug Revlimid (lenalidomide).

The data followed a disappointing announcement on Oct. 19 that Celgene will discontinue development in Crohn's disease for the late-stage drug GED-0301 (mongersen), which was followed by surprising third quarter earnings news that Otezla (apremilast) is not living up to expectations in psoriasis and psoriatic arthritis. (Also see "Celgene Admits It Screwed Up Otezla Estimates; Investors Lose Confidence" - Scrip, 26 Oct, 2017.) The company's stock dropped 16.3% Oct. 26 after the earnings results were presented to close at $99.99, following an 8.4% decline the day the GED-0301 setback was announced.

The positive presentation at ECTRIMS-ACTRIMS did little to improve investor outlook, however, given that investors were already anticipating positive data on ozanimod in MS. CEO Mark Alles said during the company's third quarter call that he expects ozanimod to be a blockbuster in MS.

However, given the competitive dynamics in the disease, with pricing pressure from payers, new therapies like Roche's Ocrevus (ocrelizumab) and the threat of fingolimod generics, investors may remain wary.

"We think investors view the launch as a show-me story," Credit Suisse analyst Alethia Young said in an Oct. 30 research note. "The label in 4Q18 might be a catalyst if it is differentiated, but we think investors might wait for sales until they assign more credit to the program." Young forecasts peak ozanimod sales of $900m for the MS indication.

Barclay’s analyst Geoff Meacham agreed on the investor sentiment. "Although we are encouraged by RADIANCE and SUNBEAM and the company's commercial plan, we continue to expect near-term skepticism on the Street," he said. "MS [key opinion leaders] we spoke to see ozanimod as primarily a successor to Gilenya – that is as a first-line option for higher-risk patients. Most were less convinced that ozanimod would be a good option for lower-risk patients, at least in the near term, where the injectables and [Biogen's Tecfidera (dimethyl fumarate)] dominate." Meacham forecasts $500m in ozanimod sales in 2019.

In SUNBEAM, ozanimod showed a significant reduction in annualized relapse rate in multiple sclerosis patients at both a 1mg and 0.5mg dose versus Avonex over an average of 13.6 months. Ozanimod also showed a significant reduction in new or enlarging T2 lesions over one year compared to Biogen's interferon. A reduction in brain-volume loss, a measure associated with MS disease progression, was also observed for the ozanimod group versus the comparator.

In terms of safety, no second-degree or higher atrioventricular blocks were reported. Infection rates were similar across treatment arms; serious infection rates were low, with no serious opportunistic infections in ozanimod-treated patients.

RADIANCE evaluated patients over two years, with similar benefits seen versus Avonex on endpoints like relapse rate, reduction in new or enlarging T2 lesions and reduction in brain-volume loss.

In a pre-specified pooled analysis of the SUNBEAM and RADIANCE Part B studies, ozanimod did not reach statistical significance compared with interferon in time to three-month confirmed disability progression, though a low rate of disability was seen in all three arms, the company reported. Again, most adverse events in RADIANCE were mild.