Yesterday’s phase II failure of Biogen’s anti-Lingo-1 antibody opicinumab lays bare the company’s reliance on high-risk CNS projects, and show just how lacklustre its late-stage R&D pipeline is.
It is remarkable how much value investors had baked into opicinumab, a multiple sclerosis project, but then management had done little to rein in expectations. Biogen’s market cap lost 13%, or $8bn, yesterday, and the question now is how the group can restock its pipeline, with licensing or acquisition likely topping investment bankers’ wish lists.
The argument in favour of business development will also have been strengthened by recent plans to spin out Biogen’s haemophilia business. At the end of the first quarter the group was sitting on $3.6bn of gross cash.
As it stands the failure of opicinumab follows that of Biogen’s Alzheimer’s disease project aducanumab, whose underwhelming efficacy coupled with a worrying side effect of vasogenic oedema prompted a sharp stock price fall a year ago.
Opicinumab’s phase II Synergy trial failed to hit its primary endpoint, a multiple measure of physical function, cognitive function and disability. A secondary endpoint focusing on disability progression was also missed, though safety – featuring in several secondary measures – was in line with previous studies, Biogen said.
The sellside seems to have been relatively cautious on opicinumab, as shown by EvaluatePharma’s consensus sales forecasts of just $323m in 2022; Leerink did not even include the anti-Lingo-1 MAb in its model, though at the height of the bull market Credit Suisse had suggested that the asset could be worth $10bn.
Yesterday’s share price collapse shows the buyside’s reliance on bullish whisper numbers, and hopes might have been fuelled by early data on Acorda Therapeutics’ rHIgM22, which like opicinumab aims to remyelinate the axons of patients’ nerve cells – seen as the holy grail of multiple sclerosis therapy.
There appear to be now only two other clinical assets aiming to do this: Abbvie’s anti-RGMa MAb ABT-555, and GlaxoSmithKline’s histamine H3 receptor antagonist GSK239512. Vertex has previously investigated Lingo-1.
But Glaxo’s phase II data were mixed, and there was negative precedent for opicinumab itself: the project last year failed in optic neuritis, an indication that was seen by some as a proxy for multiple sclerosis, since it too is characterised by loss of myelin sheaths.
Nevertheless, Biogen at the time worked hard to dress the data up as a success, focusing on an intent-to-treat analysis that it claimed was positive even though its p value was above 0.05 (Biogen struggles to get the Lingo right, January 9, 2015).
It is easy to say in hindsight, but more investors should have taken the hint back then that multiple sclerosis success was a long shot.
For now opicinunmab has not been discontinued, and Biogen stresses that because of the complexity of the result it will take some time to analyse. A presentation at the Ectrims congress in September is possible.
Biogen did say opicinumab showed a “complex, unexpected dose-response”, which might hint at higher dosing – if there are no dose-limiting toxicities. The Synergy trial tested four doses up to 100mg/kg, and the overall data could also influence development of Biogen’s oral remyelinating agent, BIIB-061, just finishing phase I studies.
It is noteworthy, however, that beyond opicinumab and aducanumab only two of Biogen’s R&D projects have 2022 sales forecasts in the hundreds of millions: Zinbryta and Ocrevus, both for MS.
While Biogen’s rival Celgene splashed out $7.2bn on Receptos last year Biogen’s most significant recent move was a relatively small licensing deal with Mitsubishi Tanabe Pharma for MT-1303. The added pressure from opicinumab’s failure could force Biogen to open its chequebook.
|Synergy||419 MS pts, 3-100mg/kg on top of Avonex||NCT01864148|