For any chance of commercial success, Colucid Pharmaceuticals’ migraine project lasmiditan needs to win approval without a cardiovascular warning on the label. Phase III data released yesterday suggest that this could well be in the company’s grasp.
Colucid intends to launch the product itself in the US, tapping in to migraine patients with cardiovascular problems who therefore cannot take triptans. However, while the data seem to confirm a benign CV profile, efficacy looks comparable at best to this now-generic class (see table).
The company clearly does not see this as a problem, and if regulators are comfortable with the safety profile the drug could be launched with a meaningful differentiator. The use of triptans is restricted in patients with CV risk factors – Colucid claims that three quarters of migraine patients in the US also have CV risks – while almost half of patients do not respond to the treatment.
Lasmiditan is triptan-like in that it targets a serotonin receptor, although it hits a different site and does not cause vasoconstriction – the cause of the triptans’ CV effects. It acts in the trigeminal nerve pathway, rather than the blood vessels like the triptans.
Efficacy looks similar to the triptans, however, and arguably weaker when compared with a triptan plus naproxen, a widely used combination to boost painkilling effects.
|Samurai trial||Cochrane Review|
|Primary endpoint||Lasmiditan 100mg||Lasmiditan 200mg||Placebo||Sumatriptan plus naproxen*||Placebo|
|Percentage of patients migraine headache pain free at two hours||28%||32%||15%||27-50%||7.7-18%|
|*Range over three studies.|
Still, this efficacy is probably sufficient to win approval, and the Samurai study reported yesterday was undoubtedly a success. As the table above shows the primary endpoint was hit, as was the secondary endpoint of percentage of patients free of the most bothersome symptoms at two hours, also with p<0.001.
Most of the side effects were nervous system-related, with dizziness, paraesthesia and somnolence being the most prevalent. Importantly there was no significant difference in the CV symptoms between the groups – 82% of patients randomised had these risk factors, so the absence of any signal will be taken as a strong safety indicator.
This must now be confirmed in a second very similar phase III trial, Spartan, due to yield results next year. And then most importantly, the FDA must concur with a benign safety profile, to help the company’s marketeers overcome the apparent lack of any efficacy advantage.
Despite the strong results, regulators will look closely at this application. On top of the climate of intense scrutiny of any possible CV danger in novel drug mechanisms, trial design could be an issue.
Although the pivotal programme is being run under an SPA, the Spartan and Samurai only tracked responses after one dose; the sort of patients who will use this drug will typically be reaching for the pill bottle several times a month.
The competitiveness of this highly genericised market is of course another headwind for Colucid, even before considering the advent of the anti-CGRP agents that are approaching the market. Although they are being developed largely for the prophylactic market, this big pharma-backed segment should not be overlooked (Marginal migraine benefit puts Amgen and Novartis in pole position, June 9, 2016).
Investors were happy to ignore all of this yesterday, however, and Colucid’s valuation more than doubled to $380m. The prospect of an inevitable fund raising was seemingly not enough to cap the enthusiasm; the company ended the second quarter with $42m in the bank, enough to last until mid-2017.
It will need to top up the coffers to get through the regulatory process and prepare for launch. Although, without a clean label, these efforts will surely come to naught.