FDA Oncology Drug Advisory Committee Recommends 9-4 Against Approval
"Concerns Over Least Effective Treatment"
ORR 28% but Side Effects in 85%
Hanmi: "Adverse Reactions Also Seen in Other Cancer Drugs"
"Need for Diverse Treatment Options"
Molecular structure image of Hanmi Pharmaceutical's non-small cell lung cancer treatment drug 'Poziotinib'
[Asia Economy Reporter Lee Chun-hee] The Oncology Drugs Advisory Committee (ODAC), an advisory panel of the U.S. Food and Drug Administration (FDA), has determined that the benefits of Hanmi Pharmaceutical's new non-small cell lung cancer treatment drug, Poziotinib, do not outweigh the risks. With the FDA approval of Rolontis, a treatment for neutropenia, Hanmi Pharmaceutical's research and development (R&D) strategy aiming for two consecutive FDA new drug launches has hit a red light.
On the 23rd, Hanmi Pharmaceutical announced that it had received a recommendation regarding the accelerated approval of Poziotinib following the FDA ODAC public hearing. ODAC voted 9 to 4 the previous day (local time) 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.
This outcome was also anticipated following the release of related materials ahead of the ODAC meeting on the 21st (local time), where ODAC expressed strong 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 Poziotinib's efficacy, citing a low objective response rate (ORR) of about 28%, which refers to the proportion of patients who show a measurable reduction in tumor size among all patients. They directly compared this to the ORR of 58% for Enhertu (trastuzumab deruxtecan), an antibody-drug conjugate (ADC) anticancer drug recently approved domestically by AstraZeneca and Daiichi Sankyo. They also pointed out that the median duration of response (mDoR) for Poziotinib is 5.1 months, which is lower than Enhertu's 8.7 months.
ODAC also viewed the safety profile of Poziotinib as concerning. Among 368 patients receiving a daily 16 mg dose of Poziotinib, 85% experienced grade 3-4 adverse events, and 57% required dose reductions, indicating low drug tolerance. While the advisory committee noted that such side effects might be mitigated in alternative dosing groups, they emphasized the need for further analysis regarding the efficacy at this dosage.
Hanmi: "Side effects are predictable and manageable... Benefits clearly outweigh risks"
Poziotinib is a pan-HER2 anticancer drug that Hanmi Pharmaceutical licensed in 2015 to Spectrum Pharmaceuticals, a U.S. company that previously licensed Rolontis. It was developed as a second-line treatment for HER2 exon 20 mutation lung cancer patients, for whom no approved therapies currently exist. Spectrum submitted a New Drug Application (NDA) to the FDA in December last year. The Prescription Drug User Fee Act (PDUFA) date for the approval decision is set for November 24.
However, with this news, concerns are growing that conditional FDA approval for Poziotinib may be difficult. Hanmi Pharmaceutical explained that since Poziotinib is a second- or third-line treatment rather than a first-line therapy, and given the nature of anticancer drugs which often have side effects, the benefit-risk balance must be considered.
A Hanmi Pharmaceutical official emphasized, "The adverse reactions reported so far are also seen with other drugs," adding, "They are sufficiently predictable and manageable, and the benefits Poziotinib provides to patients clearly outweigh the risks." Regarding usefulness, the official said, "Lung cancer has a much higher mortality rate compared to other cancer types, so patients should be offered various treatment options. Poziotinib can be administered as a second- or third-line treatment for patients who do not respond to existing therapies, and as an oral medication rather than an intravenous (IV) injection, it offers convenience in administration, which highlights its utility."
Hanmi Pharmaceutical also stressed that the ODAC advisory opinion does not determine the FDA's final approval. Hanmi stated, "The recommendations following ODAC discussions are not binding on the FDA's final approval decision," and "The FDA will review all circumstances, including ODAC's recommendations, and decide on the final approval by November 24."
Tom Lee, President of Spectrum, also said, "The ODAC result is disappointing as there is a need for additional effective treatments for lung cancer patients with HER2 exon 20 insertion mutations who have prior treatment experience," adding, "We will carefully evaluate our options for Poziotinib ahead of the PDUFA date on November 24."
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