Celiprolol Treatment Linked to Improved Survival in vEDS Patients

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by Santiago Gisler |

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Marfan Foundation

The therapy celiprolol increased the survival rate and possibly lowered annual incidence of arterial events in patients with vascular Ehlers-Danlos syndrome (vEDS), according to results of a long-term study announced by Acer Therapeutics.

The results were published in the Journal of the American College of Cardiology, in an article titled “Vascular Ehlers-Danlos Syndrome Long-Term Observational Study.

vEDS is considered the most severe EDS disease subtype. Patients with vEDS can experience ruptures, such as colonic perforation (when the tissue of the colon tears) or arterial rupture (when the wall of an artery tears). The disease currently has no approved treatment options.

Acer Therapeutics is developing a potential therapy called Edsivo (celiprolol) for the treatment of vEDS. Celiprolol is used to treat hypertension (high blood pressure), and it is thought to be of benefit to vEDS patients by reducing blood pressure in vessels most prone to dissection and rupture, and by promoting normal collagen synthesis in blood vessels.

In 2015, the U.S. Food and Drug Administration (FDA) granted Edsivo orphan drug designation for the potential treatment of vEDS.

Now, researchers described the long-term outcomes of a cohort of 144 vEDS patients followed at the French National Referral Center for Rare Vascular Diseases in Paris, France, between 2000 and 2017. Median follow-up was 5.3 years. All patients had mutations in the COL3A1 gene (disease-causing mutations).

After an initial medical exam, patients received celiprolol (up to 400 mg/day or more) together with usual care.

At the study’s start, half the patients were not receiving regular treatment, and one-third were taking celiprolol. By the end of the study, the majority of the patients (90.3%) received celiprolol alone or in combination with other therapies.

Results showed that patients treated with celiprolol had better survival (80.7%) compared with non-treated patients (48.5% survival) after 11.1 years of follow-up. Furthermore, a dose-dependent effect on survival was observed — patients treated with a median dose of 400 mg/day had a significantly higher survival rate than those receiving 217 mg/day.

According to Michael Frank, MD, clinical investigator from the Paris group and first author of the study, “the higher overall survival in patients treated with celiprolol in this long-term study in COL3A1-positive vEDS patients appears to correlate with the significant event-free survival advantage that was reported” in previous studies, he said in a news release.

The researchers also found a lower hospitalization rate for arterial events during the time of the study in which most of the vEDS patients received celiprolol, suggesting that the treatment could reduce the incidence or severity of arterial complications.

No serious adverse effects associated with the therapy were reported. Regarding the treatment dose, 62.5% of the patients remained at the maximum tolerated dose throughout the follow-up, while 3.5% (five patients) reduced the dosage because of fatigue.

“We are pleased to see this publication from the vEDS clinical investigator group in Paris which provides patients and physicians with a greater understanding of this chronic disease, including data suggesting a positive impact of celiprolol, which has a unique pharmacological profile,” said William Andrews, MD, chief medical officer of Acer.

Acer is in the process of getting its therapeutic candidate Edsivo (celiprolol) approved by the U.S. Food and Drug Administration for the treatment of vEDS.