Biogen Idec is firmly established as a multiple sclerosis powerhouse, but in recent months the attention of some of its more bullish followers has gone beyond even Tecfidera, Plegridy and daclizumab to fall on BIIB033, an early-stage anti-Lingo-1 antibody.
It is important to remember, however, that BIIB033 is an extremely high-risk project, which has yet to show clinical validation and is barely in phase II studies. This has not stopped Credit Suisse from speculating that it might be worth $10bn or more, on the strength of a mechanism – remyelination – that represents the holy grail of next-generation MS drug development.
The project is in two phase II studies, the more important of which, Synergy, does not read out until 2016. The second, Renew, is in acute optic neuritis, a condition that is sometimes the presenting sign of MS; like MS this is characterised by the loss of nerve cells’ myelin sheaths.
Still, the caution with which Biogen has spoken about BIIB033 is notable. So is the fact that it chose Wednesday’s financial call, during which it smashed forecasts, sending its stock up 11%, to rein back expectations.
Phase II readout had initially been expected this year, with analysts like ISI Group’s Mark Schoenebaum calling it one of the most important events of 2014. Biogen now says Renew will read out in 2015, while despite an interim analysis next year no data will be disclosed on Synergy until 2016.
|Phase II trials of anti-Lingo-1 MAb BIIB033|
|Renew||82 acute optic neuritis patients||100mg/kg iv vs placebo||NCT01721161||2015|
|Synergy||396 relapring-remitting MS patients||3-100mg/kg iv, on top of Avonex||NCT01864148||2016|
BIIB033’s purported mechanism tackles the neuronal demyelination that characterises MS; Lingo-1 is a protein expressed selectively in the CNS and known to prevent myelination.
As such, blocking Lingo-1 offers the possibility of actually repairing neuronal axons and myelin, in contrast to current MS treatments, which reduce clinical disease activity. Two other remyelinating approaches are in development: GlaxoSmithKline’s phase II histamine H3 receptor antagonist GSK239512, and Acorda Therapeutics’ rHIgM22, in phase I.
So, if you are an anti-Lingo-1 bull, what should you be looking for in next year’s Renew data? At best, some kind of evidence that BIIB033 is able to promote remyelination, which could provide a meaningful read-across to the later Synergy trial. At worst, of course, a serious toxicity signal could scupper the entire programme.
And why is Credit Suisse so bullish? If BIIB033 works it could become the gold standard, the analysts say, seizing as much as half the value of the total relapsing-remitting MS market with little or no competition; this might include the more advanced patients with secondary progressive disease, as well as primary progressive MS, an early-onset condition that accounts for 10% of MS cases.
Not only that, but the project could be used not only as monotherapy but also in combination with other drugs, such as Biogen’s Avonex, with which it is being dosed in the Synergy trial. This could serve as a lifecycle extension strategy for the company.
However, this is a big “if”. Despite impressive animal data, and phase I studies showing good tolerability, there is not yet any evidence that neuronal myelin can be regenerated in a real-world setting in MS patients. Yet this is what any investor willing to take a punt on the exploratory phase II studies of BIIB033 must bet on.
Credit Suisse does stress that this is a high-risk play, but speculates that “the Street underappreciates the magnitude of the reward”. EvaluatePharma consensus data see 2020 revenue of $111m, which should be expected to rise in the run-up to the Renew data.
Little wonder that Biogen has been urging caution; placing undue reliance on a single early-stage project in valuing a company with such a breadth of MS expertise seems to be a foolish tactic. That said, in the current market the exuberance is unlikely to die down any time soon.