A Boehringer Ingelheim drug now has FDA approval as an earlier treatment for lung cancers expressing a certain genetic signature, a regulatory decision handed out under the agency’s new pilot program to accelerate the review of medicines deemed important to public health or national security.
The drug, zongertinib, brand name Hernexeos, is an oral small molecule inhibitor of a protein called HER2. Last August, the FDA granted accelerated approval for the once-daily tablet as a second-line treatment for advanced cases of non-small cell lung cancer (NSCLC) with HER2 mutations. The Thursday regulatory decision permits use of the drug as a first-line treatment.
HER2-positive cancers can be aggressive, often spreading to other places such as the brain. FDA-approved targeted therapies are already available to treat cancers with this mutation. Enhertu, the Daiichi-Sankyo and AstraZeneca-partnered antibody drug conjugate, has several approvals for such cancers. But this drug is administered as an intravenous infusion. As an oral small molecule, Hernexeos offers patients less burdensome dosing. As a first-line treatment, it has an advantage over Enhertu, whose approval in NSCLC is as a second-line or later treatment.
The label expansion for Hernexeos is based on the results a single-arm, open label study that enrolled 72 patients with advanced cases of HER2-positive NSCLC who had not received a prior systemic therapy for advanced disease. Results showed a 76% overall response rate. Of those who responded to the therapy, 64% had a duration of response of six months or longer; 44% had a duration of response of 12 months or longer.
In an interview last month during the J.P. Morgan Healthcare Conference in San Francisco, Brian Hilberdink, Boehringer’s president, U.S. human pharma, said the company had submitted Hernexeo’s FDA application under the agency’s Real-Time Oncology Review pilot program, which streamlines reviews by allowing companies to submit data on a rolling basis. Last November, the FDA named Hernexeos as one of six additional therapies awarded a Commissioner’s National Priority Review Voucher (CNPV), which cuts the standard review time of 10 to 12 months down to one or two months.
The review period does not start until the FDA accepts the filing as complete. Hernexeos’s voucher covered first-line use of the drug for advanced HER2-positive NSCLC. Without the voucher, Hilberdink estimated the drug would receive a mid-year 2026 regulatory decision in this indication.
Hilberdink said Boehringer did not request or apply for a voucher. The FDA notified the company that Hernexeos was on a short list of candidates, and then later that the voucher had been granted. Hilberdink said the selection of Hernexeos for a voucher reflected the FDA’s recognition of the need to bring patients more therapies for lung cancer, specifically advanced HER2-positive NSCLC, which has limited treatment options.
“Being able to get both second-line and now first-line with the commissioner’s voucher approval on Phase 1 data, I think just speaks to the fact that the agency is trying to find ways to get these oncology treatments approved much quicker,” Hilberdink said.
Additional clinical research is ongoing that could support further expansion of Hernexeos’s label. Hilberdink said Boehringer is studying the drug in breast cancers with the HER2 mutation. That would continue the competition with Enhertu, which has first-line approval in this indication. Hernexeos also offers the potential for addressing other types of tumors carrying the mutation. The voucher awarded to Hernexeos can only be used once and does not apply to additional indications Boehringer is pursuing for the drug.
To date, the FDA has awarded 18 vouchers under the CNPV program. The first voucher recipient to win an approval was an extended-release formulation of Augmentin, an antibiotic from USAntibiotics that could help address antibiotic shortages. But speedy review from a voucher is no guarantee of a positive outcome. Two weeks ago, the FDA rejected Disc Medicine’s bitopertin for treating the rare blood disorder erythropoietic protoporphyria. The regulator asked Disc to provide more data from another clinical trial.
Photo: Mohammed Haneefa Nizamudeen, Getty Images
