FDA Rejects Ruconest Label Expansion for HAE Swelling Prevention, Citing Need for More Clinical Data

FDA Rejects Ruconest Label Expansion for HAE Swelling Prevention, Citing Need for More Clinical Data

The U.S. Food and Drug Administration has rejected Pharming’s request to expand the label of Ruconest (conestat alfa) to include routine prevention of swelling attacks caused by hereditary angioedema (HAE).

In a complete response letter indicating it had finished its review of the company’s supplemental biologics license application, the FDA requested an additional clinical trial to further assess Ruconest’s effectiveness as a prevention therapy for HAE attacks.

“While today’s FDA decision is not what we were anticipating, we look forward to working with the FDA to generate additional clinical data required to enable access for patients to use Ruconest for HAE prophylaxis,” Bruno Giannetti, MD, PhD, chief operations officer of Pharming, said in a press release.

Ruconest is an engineered version of the C1 esterase inhibitor (C1-INH), a protein that is often absent or abnormal in HAE patients. When C1-INH is not working as it should, a pro-inflammatory protein fragment called bradykinin is produced in excess, causing blood vessels to dilate and fluid to accumulate in soft tissues.

The therapy is currently approved in the U.S., Israel, and Europe for the treatment of acute swelling episodes in adults and adolescents with HAE. But trials suggest it could also work as a preventive therapy for these patients.

Ruconest has been studied in two Phase 2 trials as a prevention for swelling attacks in HAE patients.

In the first study, called OPERA (NCT00851409), researchers examined if patients had fewer angioedema attacks during an eight-week period in which they received a weekly administration of Ruconest. The trial included 25 patients and also studied how Ruconest behaved in the body, including its metabolism, absorption, and excretion.

The second study (NCT02247739) was designed to determine if Ruconest, delivered weekly or twice weekly for four weeks, was better than a placebo at lowering the number of HAE attacks. Secondary measures included the treatment’s safety and the percentage of patients seeing at least a 50% reduction in the number of attacks.

The studies “showed consistent efficacy and safety results,” the company said. In the randomized trial, patients receiving Ruconest twice weekly experienced a mean of 2.7 attacks, while those on placebo had an average of 7.2 attacks, during the four-week period.

Adverse events were more common in Ruconest-treated patients, but headaches and colds were the most common side effects reported.

In January, the FDA deemed the application — which included data from both Phase 2 trials — complete enough to submit. But after a review of the application, the agency has decided that an additional trial is needed to further study Ruconest as a preventive therapy.

“We see this as a minor setback,” said Sijmen de Vries, MD, CEO of Pharming. “We will continue and have the resources to develop new innovative and more convenient administration options of Ruconest for acute treatment and prophylaxis of HAE to improve patient care.”