The FDA has issued a complete response letter (CRL) to Spectrum Pharma for poziotinib, its pan HER2 inhibitor for a form of lung cancer, according to South Korea’s Hanmi Pharma, which originally developed the drug.
Hanmi reported the FDA’s rejection of the marketing request first, as the CRL emerged during the Thanksgiving holiday in the US and the Korean company wanted to eliminate “unnecessary misunderstandings” about the timing of the disclosure, given the time difference with the US, according to a Korea Biomedical Review Report.
Spectrum is expected to make an announcement later today, but the CRL was widely anticipated as the FDA’s Oncology Drugs Advisory Committee (ODAC) voted 9-4 against approving poziotinib in September, saying that the benefits of poziotinib do not outweigh its risks.
Spectrum has filed for accelerated approval of poziotinib as a second-line treatment for patients with non-small cell lung cancer (NSCLC) with a HER2 exon 20 insertion mutation, but the FDA remains unconvinced by the phase 2 data presented. in support of the medicine.
In review papers published ahead of the ODAC meeting, the agency questioned what it described as marginal efficacy in clinical trials of the drug, high toxicity rates and concerns about the dose selected for the study.
The phase 2 ZENITH20 trial showed an objective response rate (ORR) of 28% with a median duration of response of about five months, and 12% of patients had to discontinue therapy due to side effects.
The FDA began its standard 10-month review of poziotinib in February, with the Prescription Drug User Fee Act (PDUFA) date for a decision falling directly on the Thanksgiving holiday.
He also said he was concerned about a delay in starting a confirmatory trial of the drug, called PINNACLE, which
Spectrum has since also reported results with poziotinib as a first-line treatment for NSCLC with HER2 exon insertion mutation 20, an aggressive form of lung cancer with no approved therapies.
Up to 4% of lung cancer cases have HER2 mutations, with HER2 exon 20 changes being the most common form. However, current drugs targeting HER2 have yielded disappointing results in NSCLC despite their effectiveness in HER2+ breast and gastric cancers.
Spectrum licensed worldwide poziotinib rights – excluding Korea and China – from Hanmi in 2015.
There was better news for the partners earlier this year when Spectrum secured FDA approval for Rolvedon (eflapegrastim) to treat adults with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with febrile neutropenia.
The drug, also developed by Hanmi, was launched last month in a market that Spectrum estimates is worth about $2 billion a year.