Ablynx’s caplacizumab hits primary endpoint in phase 3

Shares in Ablynx rose 20% following the news. (Courtesy of Ablynx)

A phase 3 trial of Ablynx’s caplacizumab has met its primary endpoint. The trial linked the anti-von Willebrand factor single-domain antibody to a statistically significant drop in time to platelet count response, bolstering Ablynx’s pitch for approvals in the U.S. and Europe.

Investigators enrolled 145 patients with acute episodes of acquired thrombotic thrombocytopenic purpura (aTTP), a rare, non-hereditary condition characterized by low blood platelet counts with a mortality rate of about 15% when treated with therapeutic plasma exchange (PEX). Participants received either daily caplacizumab or placebo on top of daily PEX and immunosuppression until 30 days after the last plasma exchange. 

Ablynx developed caplacizumab to improve outcomes by blocking interactions between platelets and ultralarge von Willebrand factor multimers, which accumulate in aTTP patients and cause platelet aggregation.

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The phase 3 data suggest this has the desired effect. 

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Platelet counts of participants who received caplacizumab responded faster than those who took placebo, resulting in a statistically significant p value of 0.01. Ablynx is yet to provide further details about this primary endpoint, beyond saying “at any given time patients treated with caplacizumab 50% more likely to achieve platelet count response.”

Many observers expected the trial to hit its primary endpoint. In an earlier phase 2, caplacizumab triggered platelet responses in 3.0 days, as compared to 4.9 days for placebo. That result was good enough to support a filing for approval in Europe.

The high expectations for the phase 3 increased focus on the secondary endpoints, which are designed to go some way toward showing whether the shortened time to platelet response is significant clinically. Of the four secondary efficacy endpoints, Ablynx hit the top two on its list and missed the rest.

Caplacizumab’s effect on the percentage of patients with aTTP-related death, recurrence of aTTP or one or more major thromboembolic event landed in the success column. The clinical trial linked Ablynx’s drug to a 74% drop in these events, primarily because it outperformed placebo in terms of its effect on recurrences. 

That effect on the rate of recurrences was reflected in the other successful secondary endpoint. The proportion of patients with a recurrence of aTTP was 67% lower in the caplacizumab cohort, resulting in the trial hitting that secondary endpoint.

The trial missed the other two secondary endpoints, although caplacizumab’s performance against one of the measures couldn’t have been any better. That measure compared the numbers of patients in each arm who were refractory to the treatment. The caplacizumab cohort featured no refractory patients. But with the placebo group only containing three, the trial missed that endpoint with a p value of 0.057.

Caplacizumab also failed to statistically beat placebo against a fourth endpoint that looked at how quickly markers associated with organ damage returned to normal.  

The safety data echo those from the phase 2. As in that trial, more patients in the phase 3 who took the study drug experienced bleeding-related adverse events—66.2% versus 49.3%— but most cases were of mild to moderate severity.

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Ghent, Belgium-based Ablynx will use the phase 3 data to seek approvals of its wholly owned lead candidate in the U.S. and Europe. 

“These results strengthen our resolve to obtain marketing approval as quickly as possible so that caplacizumab rapidly becomes available to patients suffering from this severe disease for which there is currently no approved drug available,” Ablynx CEO Edwin Moses, Ph.D., said in a statement.

Shares in Ablynx opened up close to 20%.