Acorda keeps the remyelination dream alive


Though hopes for treating multiple sclerosis by promoting remyelination might still be faint, the concept got another small boost yesterday from results of an extremely early trial of Acorda Therapeutics’ rHIgM22.

These came less than a month after Biogen Idec posted highly ambiguous phase II data from its anti-Lingo-1 antibody BIIB033 – which nevertheless prompted some analysts to attach huge sales forecasts to the project. Given such excitement attention now falls on April’s American Academy of Neurology meeting, where detailed efficacy data for both could be presented.

For now, however, nothing about the efficacy of rHIgM22 is known. All Acorda disclosed was that no dose-limiting toxicities or serious adverse events had emerged at any of five doses tested in a phase I trial of 72 patients with all clinical presentations of MS, of whom 55 got rHIgM22 and 17 got placebo.

The trial was relatively robust for a first-in-man study, having a double-blinded design, and Acorda has seen enough to start planning a bigger phase I trial, which it says will enrol actively relapsing MS patients. Biotech bulls will have to guess whether this will be followed by a traditional phase II trial or a pivotal programme.

Before then signs of efficacy will be keenly awaited. Mark Schoenebaum, an analyst at ISI Evercore, said biomarker and MRI data from 21 patients followed for six months would be particularly indicative of activity.

Full data will be presented at a future scientific meeting, Acorda said, and the American Academy of Neurology conference looks a likely candidate. This is the meeting at which Biogen says it will present further analyses of its phase II multiple-dose trial of BIIB033 (Biogen struggles to get the Lingo right, January 9, 2015).

Since BIIB033 failed to hit the primary endpoint in all comers, missed all secondary measures and had only an arguably positive effect in patients who complied with the protocol, supporters of the remyelination hypothesis will look for more evidence to back this approach.

Loss of myelin

The theory is that if nerve cells can be remyelinated MS can be reversed, since the disease is characterised by the loss of myelin sheaths around the cells’ axons.

That said, this might simply be a function of extensive nerve cell damage; there has been some suggestion that the problem is not lack of ability to remyelinate, but that remyelination becomes futile because inflammation has caused too great a loss of axons and neurons – an irreversible process once it is advanced.

The MAb BIIB033 targets Lingo-1, a CNS protein known to prevent myelination, while the mechanism of rHIgM22 has not been defined, though this MAb has improved remyelination in animal models. A separate project, GlaxoSmithKline’s histamine H3 receptor antagonist GSK239512, completed a phase II trial last September, but the UK group has not revealed any of the findings.

One caveat about reading too much into Acorda’s data is that its trial was not powered to detect significant differences in the exploratory clinical biomarker measures. Moreover, this was just a single-dose study; single doses of BIIB033 failed to show an effect in an earlier trial, and rHIgM22 is thought to have a shorter half-life than the Biogen project.

These doubts will not do much to diminish exuberance. Leerink analysts already see BIIB033 generating $3.4bn of sales in 2024, to which they apply an amazing 33% chance of success; Credit Suisse last year speculated that the project could be worth over $10bn.

The industry, too, is undeterred: Biogen recently moved a small-molecule remyelinating project in to the clinic, while last June Roche formed a partnership with Versant Ventures to develop small molecules against new remyelinating targets.

Notwithstanding the scant data, and some scepticism around the approach, there is no sign that the industry is about to give up on the remyelination holy grail.

To contact the writer of this story email Jacob Plieth in London at or follow @JacobEPVantage on Twitter

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