A Cancer Driven by Ultra-Rare Mutation Gets Its First FDA-Approved Therapy

A rare type of cancer affecting the bile ducts of the liver now has its first FDA-approved targeted treatment, an intravenously infused medicine from Partner Therapeutics.

The Friday regulatory decision for the drug, Bizengri, permits its use for treating adults whose cholangiocarcinoma has progressed on or after a prior systemic therapy. The cancer must be driven by NRG1 gene fusions, the genetic signature addressed by the Partner drug. To be eligible for treatment, patients must first be tested to identify the NRG1 gene fusion.

About 8,000 cholangiocarinoma cases are diagnosed in the U.S. annually, according to the American Cancer Society. The five-year survival for this cancer is about 10% for cases that start within the liver; for cholangiocarcinoma that starts outside the liver, five-year survival is about 13%.

Cholangiocarcinoma can be driven by several types of genetic mutations. Lexington, Massachusetts-based Partner says NRG1 gene fusions are found in fewer than 1% of cholangiocarcinoma cases. Furthermore, NRG1 mutations occur in patients who are negative for other cancer drivers, leaving them without any approved targeted therapy. Bizengri is a bispecific antibody designed to bind to the cancer-driving HER3 receptor in order to prevent its interaction with NRG1 gene fusions.

Standard first-line cholangiocarcinoma treatment is chemotherapy, which comes with significant toxicity. Second-line chemo combinations lead to objective responses in about 5% of patients, according to Partner. Bizengri provides eligible cholangiocarcinoma patients with an alternative.

The FDA approval was based on the results of an open-label clinical trial that enrolled 22 patients with advanced cases NRG1 fusion-positive cholangiocarcinoma. In the 19 participants evaluable for efficacy, the overall response rate was 36.8%. The duration of response ranged from 2.8 to 12.9 months. Adverse effects reported in the trial included infusion-related reactions, diarrhea, and muscle pain.

The FDA’s approval of Bizengri for cholangiocarcinoma was particularly fast, handed out under the Commissioner’s National Priority Voucher (CNPV) pilot program. This program accelerates regulatory review of products addressing a national health interest, such as an unmet need in cancer, shaving the standard review of about 10 months down to one or two. Partner announced it submitted Bizengri’s application for FDA review on April 14, but said nothing about the CNPV program. Last Wednesday, Partner announced it had received a voucher. On Friday, the FDA announced the approval of Bizengri in cholangiocarcinoma, making it the seventh product approved under the CNPV program.

“We did not proactively apply for the voucher and rather we were encouraged to apply for it by the FDA,” Partner Chief Development Officer Pritesh Gandhi said in an email.

Bizengri was initially developed by Merus, which received accelerated FDA approval for the drug in 2024 as a treatment for pancreatic adenocarcinomas and non-small cell lung cancers that are positive for NRG1 gene fusions, making it the first drug for cancers driven by this genetic signature. Just prior to that FDA decision, privately held Partner licensed rights to commercialize Bizengri for NRG1-positive cancer in the U.S. Merus received an upfront payment, though the amount was undisclosed. Milestone and royalty payments will be paid to Genmab, which acquired Merus last year in an $8 billion deal.

Bizengri is Partner’s second commercial asset. In 2018, the company licensed global rights to sargramostim, brand name Leukine, from Sanofi. Initially approved in 1991, Leukine promotes the growth and activation of white blood cells to fight infections. Its approved uses include treating or preventing infections in patients with certain blood cancers and in patients undergoing bone marrow transplants.

Illustration: libre de droit, via Getty Images