On Tuesday, June 25th, the U.S. Food and Drug Administration ("FDA") responded to the New Drug Application that Acer Therapeutics submitted to bring celiprolol (under the brand name Edsivo) to the U.S. as a treatment for vascular Ehlers-Danlos Syndrome ("vEDS"). In the response, the FDA declined the application, requesting a new trial to demonstrate the impact of celiprolol in vEDS.
We will make a series of posts that discuss the future of vEDS treatments, but we don't believe this recent decision is bad news. The good news is there may still be opportunities to get celiprolol for vEDS and - maybe even more exciting - the FIGHT vEDS team is following new research that may provide groundbreaking treatments in the next few years that could be more effective than celiprolol. We will be sharing some of those details in upcoming posts (subscribe here for updates) but today we'll break down the recent FDA decision.
THE HISTORY OF CELIPROLOL IN THE US
In December 2016, Acer Therapeutics made an agreement with French researchers to use their study data in Acer's FDA submission. In 2018, Acer submitted their application, which was accepted on December 26, 2018 with a priority review - meaning that the FDA would reply by June 25, 2019.
In their application, Acer relied primarily on two studies to provide evidence that celiprolol works:
The 2010 BBEST trial of 53 patients on celiprolol in Europe
The 2019 longitudinal study reviewing management and outcomes of vEDS patients at a single national referral center in Paris, France
The 2019 study came out on April 16, 2019. Although the research showed that vEDS patients in France were living longer, it wasn't clear what role celiprolol played (see our blog post breaking down that study). Acer's stock dropped ~20% following the publication of these data, indicating that many investors felt the research was not as compelling in support of celiprolol as they'd hoped.
On Tuesday, June 25, 2019 Acer received a complete response letter ("CRL") from the U.S. FDA regarding its application for Edsivo (celiprolol). The CRL says Acer will have to conduct an adequate and well-controlled trial to determine whether celiprolol lowers the risk of clinical events in patients with vEDS. Immediately following the news Acer's stock declined about 80%, which can be seen in the image below.
Source: Yahoo Finance
WHY THE RESPONSE MAKES SENSE
Although some were surprised by the FDA's decision - many believed the data from the trials was not sufficient to support an FDA approval. The 2010 BBEST trial has been criticized for the small sample size (53 patients) and the fact that initially these patients were not confirmed with a genetic test to ensure they had vEDS. In fact, during the course of the study the researchers learned that 20 of the patients enrolled did not actually have a COL3A1 mutation. This means that only 33 patients in this already small trial actually had a mutation in COL3A1, the gene that causes vascular EDS (see our research page to learn more about the BBEST trial).
The 2019 longitudinal study showed positive results but even the researchers that conducted the study concluded in their paper:
"It is difficult to formally assess this beneficial effect (the benefit of celiprolol on survival) in the absence of a placebo-controlled prospective trial."
It makes sense that the FDA required Acer to formally assess the benefit of celiprolol, as they did (see our research page to learn more about the 2019 longitudinal study).
WHERE DO WE GO FROM HERE?
Some vEDS patients wanting a treatment may be disappointed by this news, but don't be. We believe there is positive news on the horizon in light of the recent FDA decision:
The FDA has requested Acer perform a trial that once-and-for-all can demonstrate a positive effect of celiprolol, something that the vEDS medical community has debated for a decade
There is exciting research at Johns Hopkins that, once published, could provide exciting alternative treatments to celiprolol. The next step would be evaluation of the new treatment in a clinical research trial with vEDS patients
For those who were excited by celiprolol specifically, there may be ways to get access to the drug even without FDA approval
We will update you as we have more information on each of the items above - please subscribe to our website for updates.