Zeno Gets Breakthrough Therapy Designation for NRG1+ Pancreatic Cancer

The FDA granted Zeno a Breathrough Therapy Designation for certain patients with pancreatic cancer after the drug showed promise in clinical trials.

The Food and Drug Administration (FDA) granted a Breakthrough Therapy Designation to Zeno (zenocutuzumab) for the treatment of patients with advanced, unresectable (unable to be surgically removed) or metastatic NRG1 fusion pancreatic cancer that has gotten worse with a prior systemic therapy and has no other satisfactory treatment options, according to a press release from Merus N.V., the pharmaceutical company manufacturing the drug.

The FDA grants Breakthrough Therapy Designation to drugs for serious or life-threatening conditions that could lead to better outcomes than what is already available. In doing so, the agency agrees to expedite the review of the drug and to help guide its development toward a potential Biologics License Application, which allows a drug to be introduced to the market.

“We believe the compelling clinical data for Zeno in NRG1-positive cancer, and Breakthrough Therapy Designation, provide the opportunity to further engage with the FDA to expedite the review of a potential (Biologics License Application) submission,” Dr. Bill Lundberg, president and chief executive officer of Merus, said in the press release.

The Breakthrough Therapy Designation for Zeno is based off findings from the ongoing phase 1/2 eNRGy trial and Early Access Program (EAP), each of which are investigating the safety and cancer-fighting capabilities of Zeno in NRG1-positive cancer. So far, approximately 175 patients with NRG1-positive cancers have been treated with Zeno.

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According to data from eNRGy that was presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, 34% of patients experienced a response from treatment with Zeno, meaning that their tumors shrunk or disappeared, and the average duration of response was 9.1 months. This data was pooled from a group of 79 patients with different solid cancers — all of which harbored an NRG1 fusion.

This finding, ““compares very favorably to the alternative treatment options in this setting, typically palliative chemotherapy,” said lead study author, Dr. Alison M. Schram, of Memorial Sloan Kettering Cancer Center, to ASCO.

The majority of side effects seen among the 208 patients treated with the recommended dose of Zeno were mild (grade 1 or 2). Patients most commonly experienced diarrhea (21%), infusion-related reactions (15%) and fatigue (12%). Five percent of patients experienced moderate to severe (grade 3 or 4) side effects.

Zeno works by inhibiting the neuregulin (NRG)/HER3 tumor-signaling pathway, which is essential to the growth and survival of cancer cells.

For eNRGy and EAP, Zeno is being administered as a single agent (without any other accompanying drugs), but the press release also mentioned that more research is currently underway, evaluating Zeno plus androgen-deprivation therapy — Xtandi (enzalutamide) or Zytiga (abiraterone) — for patients with castration-resistant prostate cancer, regardless of their NRG1 status.

The current Breakthrough Therapy Designation comes after a January 2021 Fast Track Designation for Zeno in the setting of solid tumors with NRG1 fusions and a July 2020 Orphan Drug Designation for patients with pancreatic cancer.

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