Ozanimod safety still a question mark for Celgene

A first phase III win for Celgene’s ozanimod puts the project on track for approval in multiple sclerosis and goes some way to justifying the $7.2bn that the company paid for its originator, Receptos.

But, with safety data still thin on the ground, it is unclear whether ozanimod will get a more favourable label than Novartis’s rival sphingosine-1-phosphate modulator Gilenya. And, with a relatively crowded S1P pipeline, ozanimod needs to set itself apart if Celgene is to recoup its investment (see table below).

Gilenya lowers heart rate, and patients need to be monitored for at least six hours after the first dose; it can also cause liver problems and its label requires liver enzyme testing before beginning treatment. The theory is that ozanimod could avoid this problem because it is more selective, targeting S1P 1 and 5, while Gilenya binds to S1P receptors 1, 3, 4 and 5.

Celgene will need to prove that this translates into a safety advantage if ozanimod is to hit the peak $4-6bn in sales – in MS and ulcerative colitis combined – that the company forecast at the time of its purchase of Receptos (Celgene confident as Receptos waiting game begins, July 20, 2015). Current EvaluatePharma sellside consensus puts 2022 revenues at $2.1bn.

Safety first

At the moment, Celgene is only saying that topline data from the phase III Sunbeam trial show a safety and tolerability profile that is consistent with previously reported phase II studies in relapsing MS and ulcerative colitis.

The earlier data are promising: in the phase II Radiance study in MS, there was a single incidence of bradycardia in a patient with a history of the issue, and patients had a mean overall reduction in heart rate of less than 2bpm, versus 8.1bpm for Gilenya, noted Evercore ISI analyst Mark Schoenebaum.

But Celgene will need to confirm this with more detailed safety data from both Sunbeam and the phase III portion of Radiance, which is due to report in the second quarter. Celgene plans to file ozanimod for approval by the end of the year.

The company is taking a cautious stance, with its chief operating officer, Jacqualyn Fouse, recently saying she assumed that ozanimod would get the same class labelling for safety as other S1P modulators.

If ozanimod does not require first-dose monitoring, however, this could help Celgene grab market share from Gilenya – and defend against Gilenya generics, which could be on the market as early as 2019.

Sunbeam

The positive efficacy results in Sunbeam, meanwhile, had been expected, but will still be a relief to Celgene. Ozanimod showed superiority to Biogen’s Avonex at both doses studied, 0.5mg and 1mg, on the primary endpoint of annualised relapse rate.

It was also better on the secondary endpoints of the number of gadolinium-enhancing MRI lesions and number of new or enlarging T2 MRI lesions at month 12. Celgene did not give any more details, and no doubt plans to present more comprehensive data at an upcoming meeting.

S1P modulators for multiple sclerosis
Project Company Mechanism Status 2022e sales ($m)
Gilenya Novartis Pan S1P modulator Marketed 1,375
Ozanimod Celgene S1P 1 & 5 modulator Phase III 2,127
Siponimod/BAF312 Novartis S1P 1 & 5 modulator Phase III 865
Ponesimod Actelion/J&J S1P 1 agonist Phase III 88
Amiselimod/MT-1303 Mitsubishi Tanabe S1P 1 antagonist Phase II 1
Source: EvaluatePharma.

If ozanimod does get approved next year as hoped, it will have a head start on other more selective S1P modulators. Actelion’s – now J&J’s – ponesimod is due to report data from the Optimum phase III trial in relapsing MS in 2019, while Novartis’s siponimod is in a phase III trial in another form of MS, secondary progressive, with a primary completion date of December 2020.

Meanwhile, Biogen dropped the phase II candidate amiselimod in October, leaving its partner Mitsubishi Tanabe Pharma to continue development alone or try to find a new licensee.

For now things are looking good for Celgene, and investors will hope that further positive results in MS could spur an increase in its 2020 sales guidance, which currently stands at $21bn. Ozanimod could be a sizeable contributor if its safety lives up to expectations – something that still needs to be proved.

Project Study Trial ID
Ozanimod Sunbeam NCT02294058
Ozanimod Radiance NCT02047734
Ponesimod Optimum NCT02425644

To contact the writer of this story email Madeleine Armstrong in London at madeleinea@epvantage.com or follow @ByMadeleineA on Twitter

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