Bizengri gets FDA approval for advanced pancreatic cancer
Accelerated approval also covers NSCLC with NRG1 gene fusion
Bizengri (zenocutuzumab-zbco) is now approved in the U.S. as the first treatment for advanced pancreatic cancer and non-small cell lung cancer (NSCLC) harboring an NRG1 gene fusion, developer Merus said.
The U.S. Food and Drug Administration (FDA) granted accelerated approval to Bizengri for use in adults with advanced pancreatic adenocarcinoma or NSCLC that has progressed despite earlier treatment and is unresectable (meaning it cannot be removed with surgery) or metastatic (meaning it has spread to another part of the body).
Accelerated approval allows early access to promising medications for serious conditions lacking effective treatments. It also means that Bizengri’s continued availability is contingent upon further clinical trials demonstrating its safety and efficacy.
“The FDA approval of Bizengri marks an important milestone for patients with pancreatic adenocarcinoma or NSCLC that is advanced unresectable or metastatic and harbors the NRG1 gene fusion,” Alison Schram, MD, an attending medical oncologist at Memorial Sloan Kettering Cancer Center in New York, said in a Merus press release.
Schram, the principal investigator who’s leading the ongoing eNRGy trial (NCT02912949) that provided Phase 2 clinical data as the basis for approval filings, said, “I have seen firsthand how treatment with Bizengri can deliver clinically meaningful outcomes for patients.”
Targeting genetic alteration
An NRG1 fusion is a genetic alteration found in a small number of solid tumors, including those forming in the pancreas or the lungs. As a result of the gene fusion, too much or faulty versions of the growth factor NRG1 are produced. NRG1 can cause tumor cells to grow in an uncontrolled way by acting on a protein receptor called HER3, which needs HER2 to signal into tumor cells.
Bizengri is a dual-targeting antibody that binds both HER2 and HER3 protein receptors using Merus’ Dock & Block mechanism of action. It docks to HER2 on cancer cells, blocking HER3 from interacting with both the NRG1 fusion and HER2. This blocks the signals that these tumors, which don’t usually respond well to standard treatment options, use to grow and survive.
Given as an intravenous (into-the-vein) infusion over four hours, the recommended dose for Bizengri is 750 mg every two weeks until cancer progresses or side effects become intolerable.
“Bizengri is Merus’ first approved medicine based on our highly innovative and proprietary Biclonics technology platform,” said Shannon Campbell, the company’s chief commercial officer. “This approval is a testament to both our technology and strong execution as we continue to develop our multispecific platforms and pipeline.”
Bizengri’s approval drew on data from eNRGy, an open-label Phase 2 clinical trial designed to test Bizengri’s safety and efficacy in 30 adults with NRG1 fusion-positive pancreatic adenocarcinoma and 64 adults with NRG1 fusion-positive NSCLC whose cancer progressed following standard of care.
The main goal was to measure overall response rate (the proportion of patients with a partial or complete response to the treatment) and duration of response. For pancreatic cancer, the overall response rate was 40%, and duration of response ranged from 3.7 months to 16.6 months. For NSCLC, overall response rate was 33% with a 7.4-month median duration of response.
The most common side effects reported with Bizengri during clinical testing included diarrhea, muscle and joint pain, tiredness, nausea, infusion-related reactions, breathing difficulty, skin rash, constipation, vomiting, stomach pain, and swelling.
Bizengri carries a serious warning, known as a boxed warning, for potential harm to a developing fetus during pregnancy.
Edward Abrahams, PhD, president of the Personalized Medicine Coalition, said the Washington-based advocacy organization “applauds the approval of Bizengri.” Abrahams added that “in keeping with the growing number of personalized medicines on the market today, Bizengri offers the only approved NRG1+ therapy for patients with these difficult-to-treat cancers.”
Merus recently entered into a partnership with Partner Therapeutics, granting Partner exclusive rights to market Bizengri in the U.S. In return, the company receives an upfront payment, milestone bonuses, and royalties of up to 12% based on yearly sales.
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