Request for Supplement, Not Rejection
FDA Advisory Committee: "Risk > Benefit"
[Asia Economy Reporter Lee Chun-hee] Hanmi Pharmaceutical's non-small cell lung cancer treatment new drug 'Poziotinib' has had its U.S. approval put on hold.
On the 25th, Hanmi Pharmaceutical announced that its partner, Spectrum Pharmaceuticals, received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) the day before, stating that "Poziotinib cannot be approved at this time." The previous day was the deadline set by the FDA under the Prescription Drug User Fee Act (PDUFA) for the decision on Poziotinib's marketing approval.
Earlier, in September, the FDA Oncology Drug Advisory Committee (ODAC) issued a negative recommendation, raising concerns that approval might be denied, but for now, with the receipt of the CRL, the approval appears to be on hold. A CRL is a formal letter sent by the FDA after a comprehensive review of a New Drug Application (NDA), indicating that additional actions are required. In other words, while immediate approval is unlikely, the FDA intends to review the application again after the necessary supplements are provided.
Hanmi Pharmaceutical's neutropenia treatment 'Rolontis,' which had raised expectations for a second consecutive FDA approval within the year after receiving FDA approval in September, also received a CRL from the FDA in 2021. At that time, the FDA delayed approval due to the need for supplements related to manufacturing inspections.
Poziotinib is a pan-HER2 anticancer agent that Hanmi Pharmaceutical licensed to Spectrum, which had previously licensed Rolontis, in 2015. It was developed as a second-line treatment for HER2 exon 20 mutation lung cancer patients, for whom no officially approved treatments exist. Spectrum submitted a New Drug Application (NDA) to the FDA in December last year.
However, ODAC voted 9 to 4 that "the benefits of Poziotinib do not outweigh the risks." ODAC is an independent advisory committee composed of experts who review and evaluate data on the efficacy and safety of anticancer drugs. ODAC strongly expressed concerns about Poziotinib's efficacy, stating, "If granted accelerated approval, this would be the least effective targeted therapy for lung cancer approved to date."
ODAC questioned the efficacy by pointing out Poziotinib's objective response rate (ORR) of about 28%, which is low. They compared it to AstraZeneca-Daiichi Sankyo's antibody-drug conjugate (ADC) anticancer new drug 'Enhertu,' which has an ORR of 58%. They also noted that the median duration of response (mDoR) for Poziotinib is 5.1 months, lower than Enhertu's 8.7 months.
Furthermore, ODAC expressed significant concerns about Poziotinib's safety profile. Among 368 patients receiving 16 mg once daily dosing of Poziotinib, 85% experienced grade 3-4 adverse events, and 57% required dose reductions, indicating low drug tolerability. The advisory committee mentioned that while such side effects might be mitigated in alternative dosing groups, additional analysis is needed regarding the efficacy at the current dose.
Portion of the briefing document from the U.S. Food and Drug Administration (FDA) Oncology Drugs Advisory Committee (ODAC) mentioning the efficacy of Hanmi Pharmaceutical's non-small cell lung cancer treatment 'Pocetinyb'
Spectrum and Hanmi Pharmaceutical plan to disclose detailed information soon due to holidays and other issues. Spectrum stated that since the FDA notification coincided with the U.S. Thanksgiving holiday on the 24th (local time), detailed information will be released the following morning (the evening of the 25th Korean time). Hanmi Pharmaceutical also disclosed the receipt of the CRL first, considering that Spectrum's announcement would be made on Friday evening Korean time, and plans to share Spectrum's announcement domestically later.
© The Asia Business Daily(www.asiae.co.kr). All rights reserved.
