After its recent missteps Celgene needed its multiple sclerosis candidate ozanimod to report knock-out results at the Ectrims meeting. But in the event ozanimod looks like an also-ran, with the latest data hardly justifying the $7.2bn that Celgene had paid for the project’s originator, Receptos.
On the all-important safety question, ozanimod appears better than Novartis’s rival sphingosine-1-phosphate modulator Gilenya. But ozanimod’s efficacy seems similar, at best, and with generic versions of Gilenya set to enter the market in 2019 there are questions over whether its safety advantage alone will allow it to command a premium in a crowded MS sector (see table below).
Investors sent Celgene’s share price down 2% on Friday when the first MS data were released – a day after the company’s stock was routed following a disastrous third quarter (Celgene slide piles pressure on Revlimid, October 26, 2017). However, shares opened up nearly 2% this morning.
True, the Sunbeam and Radiance MS trials were a success, and ozanimod’s approval in its first indication looks likely. The company plans to file the project in MS by the end of the year in the US, and in the first half of 2018 in Europe.
On the strength of the latest data, ozanimod might get a more favourable safety label than Gilenya. This would give it a shot at capturing some of that product’s sales, which totalled $3.1bn in 2016.
Gilenya’s side effects are particularly burdensome: as it lowers the heart rate patients need to be monitored for at least six hours after the first dose. Novartis’s drug can also cause liver problems, and its label requires liver enzyme testing before beginning treatment.
And Celgene’s hypothesis – that ozanimod could avoid Gilenya’s problems because it is more selective – seems to have been borne out.
On heart rate, the largest mean supine reduction seen with ozanimod was 1.8bpm at hour five, versus a decrease of 8bpm seen in previous trials of Gilenya. Liver enzyme increases also appear to be less of a problem with ozanimod than with Gilenya.
However, this might not be as important as Celgene hopes once Gilenya is genericised, expected by 2019. Stifel analysts asked: “Would a payer fork over $65,000 annually rather than $1,000 to avoid a 66% reduction in transient liver enzyme elevation in the first year?”
Efficacy lacks Radiance
This could be a tough argument for Celgene to win, particularly with ozanimod looking distinctly average on efficacy. Sunbeam and Radiance both met their primary endpoint, finding a significant reduction in the annualised relapse rate at one year versus Biogen’s interferon Avonex; the topline wins had already been reported.
Celgene unveiled more details at the Ectrims conference in Paris, specifically a 38-48% decrease in relapse rate with the higher dose of ozanimod that looks at best to be in line with the 50% reduction reported in previous trials of Gilenya. As usual, caution is warranted when making across-trial comparisons.
It is not just Gilenya that Celgene needs to worry about – ozanimod’s efficacy also appears unimpressive compared with the current MS drug to beat, Roche’s Ocrevus. The latter has been shown to reduce relapses by around 50%, but has also stopped the development of new inflammatory lesions after around six months.
And Ocrevus has significantly improved disability progression at three months, something that ozanimod was unable to do in a pooled analysis of Sunbeam and Radiance. Celgene blamed a low overall rate of disability progression in its trials.
Celgene sees oral ozanimod as a good first-line or first-switch option, with injectable therapies like Ocrevus being used in later-line patients as their potency is balanced against side effects.
Still, Ocrevus is forecast to be the biggest MS product in 2022, according to EvaluatePharma sellside consensus – and ozanimod does not even make it into the top 10, with its MS sales expected to hit $589m that year.
|Top MS drugs in 2022|
|Global sales by indication ($m)|
|Product||Company||Pharma class||Route of admin||MS status||2016||2018e||2020e||2022e|
|Aubagio||Sanofi||PDGFr TK & DHODH inhibitor||Oral||Marketed||1,433||2,018||2,152||1,673|
|Tysabri||Biogen||Anti-VLA 4 MAb||Injected||Marketed||1,964||1,704||1,435||1,315|
|Rebif||Merck KGaA||Interferon beta||Injected||Marketed||1,926||1,643||1,351||1,075|
|Siponimod||Novartis||S1P 1 & 5 modulator||Oral||Phase III||-||-||353||916|
|Copaxone||Teva||Multiple sclerosis agent||Injected||Marketed||4,223||2,234||1,235||897|
Assuming that ozanimod gets approved, chances of success could hinge on its label. While the Stifel analysts think it unlikely for ozanimod to avoid a cardiac monitoring requirement, Mizuho is more optimistic, saying that this might only be needed in a high-risk population – those with a low resting heart rate or history or cardiac disease, for example.
Pricing could also be a factor, but Celgene executives did not give any clues about this during a call to discuss the Ectrims data. Notably, Roche went in low with Ocrevus in spite of its impressive data, so again Celgene might find it hard to compete.
The Mizuho analysts do not see ozanimod as a game changer, but reckon it could have a place as a “safer Gilenya”. The project also has potential in other autoimmune disorders, with ulcerative colitis the next most-advanced indication.
The latest data are not a disaster for Celgene – but they are not the home run the company needed to justify the billions it spent on ozanimod.