Bayer’s Hyrnuo Wins FDA Approval for HER2-Mutated NSCLC, Joins Boehringer’s Hernexeos in the Space

The FDA has granted accelerated approval to Bayer’s new oncology offering Hyrnuo (sevabertinib) for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) that harbors HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations and has progressed after prior systemic therapy.

Lung cancer remains the leading cause of cancer-related deaths globally, with NSCLC representing more than 85% of all cases.

Around 80% of people diagnosed with NSCLC have typically already progressed to advanced stages, making treatment more challenging with limited treatment options. NSCLC comprises the vast majority of lung cancer cases worldwide, and a small subset (about 2% to 4%) are driven by activating mutations in the HER2 gene. These mutations are associated with poor outcomes using conventional therapies.

Related: Hernexeos (Zongertinib): First Oral HER2-Targeted TKI Wins FDA Nod in NSCLC

Hyrnuo is an oral, reversible tyrosine kinase inhibitor (TKI) designed to block aberrant HER2 signaling that drives tumor progression in this genetically defined group of patients. The drug is taken twice daily and represents a significant new option for patients whose disease has advanced despite prior treatments.

Boehringer Ingelheim’s TKI Hernexeos (zongertinib) beat out Bayer’s Hyrnuo by a few months in the approval race with an FDA nod in August in the same indication. Both drugs target the same mutations, but Bayer’s Hyrnuo is approved for locally advanced or metastatic non‑squamous NSCLC, while Hernexeos covers unresectable or metastatic disease.

“Globally, it is estimated that up to 84,000 people are diagnosed with NSCLC harboring a HER2 mutation each year,” said Christian Rommel, PhD, head of Research and Development at Bayer’s Pharmaceuticals Division.

“Today’s FDA approval of sevabertinib exemplifies this approach, delivering a targeted treatment specifically for patients with advanced HER2-mutant NSCLC. This significant milestone underscores our unwavering commitment to transforming cancer care by delivering meaningful therapies that have the potential to improve outcomes and extend survival for people living with cancer.”

The FDA’s accelerated approval of Hyrnuo is based on objective response rate (ORR) and duration of response (DoR) data from the ongoing Phase I/II SOHO-01 trial, which enrolled adults with locally advanced or metastatic HER2-mutant NSCLC who had received prior systemic therapy.

In the trial, among patients with HER2 TKD activating mutations who were naive to HER2-targeted therapy, a confirmed ORR of 71% was observed, including complete and partial tumor responses.

The median duration of response was 9.2 months, with many patients maintaining benefit for at least six months.

Responses were seen with a manageable safety profile, though common side effects included diarrhea, rash, paronychia, stomatitis and nausea.

Because the approval is accelerated, continued marketing of Hyrnuo will depend on verification and description of clinical benefit in confirmatory trials.

“The FDA’s approval of sevabertinib elevates the standard of care and provides a new treatment option for patients living with HER2-mutant NSCLC, which is a challenging disease with limited therapies available,” said SOHO-01 lead trialist, Xiuning Le, MD, PhD, The University of Texas MD Anderson Cancer Center, Houston, Texas, in a statement from Bayer. “Clinical results from the SOHO-01 trial showed that sevabertinib is effective with a manageable safety profile.”

The FDA also simultaneously cleared the Thermo Fisher Scientific Oncomine Dx Target Test as a companion diagnostic to identify patients whose tumors carry HER2 TKD activating mutations eligible for Hyrnuo therapy.

Hyrnuo is indicated for adults with locally advanced or metastatic non-squamous NSCLC with HER2 TKD activating mutations detected by an FDA-approved test and who have received prior systemic therapy.

The drug is taken orally, typically 20 mg twice daily with food until disease progression or unacceptable toxicity.

In Boehringer Ingelheim’s Lung‑1 Phase IIb trial, Hernexeos achieved an ORR of 75% among 71 patients who had previously received platinum-based chemotherapy but had not been treated with a HER2-targeted TKI or ADC. Notably, 58% of responders maintained their response for at least six months.

Bayer is now closely pursuing the same patient population, with both companies aiming to expand into the first-line treatment setting.

The list price for Hyrnuo is around $24,000 per month, compared to $21,172 for Hernexeos for one month of treatment.

At last month’s European Society of Medical Oncology (ESMO) congress, each company presented encouraging data from studies in treatment-naïve patients, showing largely comparable outcomes: Boehringer reported a 77% ORR, while Bayer’s Hyrnuo demonstrated a 71% ORR in a similar cohort.