The US Food and Drug Administration (FDA) has granted accelerated approval to Merus’ Bizengri (zenocutuzumab-zbco) for the treatment of metastatic non-small cell lung cancer (NSCLC) and advanced pancreatic adenocarcinoma with NRG1 gene fusions in patients who have had disease progression during or after prior systemic therapy.
The approval makes Bizengri the first and only treatment for cancers that have a NRG1 gene fusion. It also marks the first product approval for Netherlands-based Merus, which also has a US location in Cambridge, Massachusetts.
Zenocutuzumab-zbco is a first-in-class bispecific antibody that targets NRG1 fusions, a rare genetic driver implicated in several tumor types. It binds to the extracellular domains of the human epidermal growth factor receptors (HER) HER2 and HER3, which are expressed on the surface of cells, including tumor cells.
The drug inhibits HER2:HER3 dimerization to prevent NRG1 binding to HER3 and subsequent activation of the NRG1/HER3 signaling pathway, which promotes tumor growth and survival through the phosphoinositide 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) pathway. Bizengri also elicits antibody-dependent cellular cytotoxicity.
NRG1 fusions are rare but actionable genetic alterations, occurring in approximately 0.2 to 0.3 percent of NSCLC and 0.3 percent of pancreatic adenocarcinoma cases.
In a news release announcing Bizengri’s approval, Merus said it believes the approval fills an important need for patients with NRG1+ cancer who have not previously had treatment options approved to specifically target this driver.
The company also shared that it plans to make Bizengri 20 mg/mL injection for intravenous use available to patients in the coming weeks.
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“Bizengri is Merus’s first approved medicine based on our highly innovative and proprietary Biclonics technology platform and offers significant promise for patients with NRG1+ pancreatic adenocarcinoma and NRG1+ NSCLC,” said Shannon Campbell, chief commercial officer of Merus in a news release from the company.
Bizengri’s approval came earlier than its anticipated February 4, 2025, Prescription Drug User Fee Act (PDUFA) decision date. This was an extension of the original date as the FDA wanted more time to review additional information about chemistry, manufacturing and controls.
The FDA’s approval was based on results from the multicenter, open-label eNRGy trial that enrolled 30 patients with NRG1+ pancreatic adenocarcinoma and 64 patients with NRG1+ NSCLC that is advanced unresectable or metastatic and had disease progression on or after prior systemic therapy.
The therapy demonstrated an overall response rate (ORR) of 33 percent in NSCLC patients and 40 percent in those with pancreatic adenocarcinoma, with durable responses lasting six months or longer in a majority of responders.
Duration of response (DOR) in NRG1+ pancreatic adenocarcinoma patients treated with zenocutuzumab-zbco ranged from 3.7 months to 16.6 months. In NRG1+ NSCLC patients, the median DOR was 7.4 months.
Zenocutuzumab-zbco was generally well-tolerated in clinical trials. The most common side effects included fatigue, infusion-related reactions and gastrointestinal symptoms such as nausea and diarrhea. Serious adverse events were rare, occurring in less than five percent of patients, and were primarily related to infusion reactions.
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As part of the accelerated approval pathway, Merus is required to conduct confirmatory trials to verify the clinical benefits of zenocutuzumab-zbco. These trials are already underway and aim to provide additional data on the therapy’s efficacy and safety in a broader patient population.
Bizengri carries a boxed warning for the risk of embryo-fetal toxicity.
Merus said it plans to provide comprehensive support programs like PTx Assist to facilitate access and ensure proper use of the therapy in clinical settings.
The company had another win recently as it finally confirmed Partner Therapeutics as its commercialization partner for Bizengri.
Merus is also busy advancing its EGFR-LGR5 bispecific petosemtamab. At the start of the month, Merus shared Phase II data supporting petosemtamab’s potential to become a new standard of care for previously treated patients with recurrent or metastatic head and neck squamous cell carcinoma.
On Bizengri’s approval and the company’s future plans, Campbell said, “This approval is a testament to both our technology and strong execution as we continue to develop our multispecific platforms and pipeline, including our lead asset petosemtamab.”
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