Failure of Phase II cannabidiol trial leads to loss for Zynerba

Zynerba Pharmaceuticals’ phase II trial for transdermal cannabinoid candidate missed all its endpoints, as it failed to hit a single goal or show a dose response raises big doubts about the drug’s prospects. This news eroded around 55% off Zynerba’s stock price. 188 enrolled adults with refractory epilepsy with focal seizures were randomized to receive one of two doses of ZYN002 or placebo. Zynerba hoped to show its cannabidiol gel cut focal seizures but ultimately it fell short of that goal. Participants who received the low dose of ZYN002 experienced an 18.4% median reduction in focal seizures. The figures for the high dose and placebo were 14.0% and 8.7%, respectively. That resulted in the trial missing its primary endpoint. The endpoint miss and lack of a dose-dependent response may point to the failure of the delivery system to generate the needed pharmacokinetic profile. The secondary endpoints brought no solace to Zynerba. ZYN002 failed to beat placebo against any of the secondary goals. That left Zynerba clinging to the safety data as the sole positive.

A midstage trial of MyoKardia aims to transform inherited heart disease symptoms

MyoKardia just announced that its experimental drug mavacamten improved heart function in patients with an inherited cardiac condition, with eight of 10 showing normal readings after treatment with the drug. It is the first major clinical test for the South San Francisco biotech’s lead drug candidate, which is partnered with Sanofi, and the top-line data had pushed shares up by a third in out-of-hours trading at the time of writing. Former Fierce 15 company MyoKardia says it is now working on the design of its next trial in patients with symptomatic, obstructive hypertrophic cardiomyopathy (oHCM) which could start later this year and potentially be the basis of a regulatory filing—something it hopes to discuss with the FDA “as soon as possible.” HCM is a genetic disorder affecting about one in 500 people in which a defect in the proteins that help control cardiac contraction cause the muscle wall in the heart to become thickened. In some patients, HCM is relatively benign, but if the wall thickening blocks the flow of blood in the heart, as is the case in oHCM, it can cause severe symptoms and sudden death.

Europe is being seen as first market for gene therapies by Bluebird Bio

Bluebird Bio plans to bring its gene therapies to market in Europe before the U.S., thanks to a favorable regulatory pathway. Bluebird’s head of Europe, Andrew Obenshain, told the Daily Telegraph that the company is already in negotiations with the EMA and the U.K.’s Medicine and Healthcare products Regulatory Agency (MHRA) on possible regulatory filings. The EMA’s adaptive pathways process—which allows new therapies to be approved in stages based on a stepwise collection of data—is a key part of that decision, as is the fact that the agency “works very closely with companies coming forward with new methodologies,” said Morgan. And with Brexit looming, it makes sense to discuss these plans with the MHRA separately. Two years ago, Bluebird—which targets severe genetic diseases and cancer—was hit hard when the NorthStar trial of lead therapy LentiGlobin failed to hit the mark in sickle cell disease and beta thalassemia, mainly because of variable patient responses to the treatment.

Disappointment on ex-Pfizer LDL drug data leads to loss on Gemphire stock

Gemphire Therapeutics has posted data on its oral inhibitor of cholesterol production. The phase 2b met its primary endpoint but also linked gemcabene to a smaller-than-hoped drop in LDL cholesterol, raising doubts about the commercial viability of the asset. Investigators enrolled 105 patients with elevated levels of LDL and randomized them to receive either gemcabene or placebo. Subjects continued to take statins and, in some cases, Merck’s Zetia. After 12 weeks, investigators assessed the change in each patient’s LDL-C from their baseline level. The 17.2% decline in LDL-C in the gemcabene arm bettered the 5.5% seen in the placebo cohort. But the placebo-adjusted decline of 11.7% is lower than seen in previous studies. An earlier, 8-week phase 2 linked gemcabene to placebo-adjusted declines of greater than 20%, although the participants in that trial had higher starting levels of LDL-C. Gemphire acknowledged the gap between data from the trials in its release of the top-line results.