US-based Spectrum Pharmaceuticals Inc. (Nasdaq: SPPI) announced last week that its New Drug Application (NDA) for poziotinib, a treatment for previously treated locally advanced or metastatic non-small cell lung cancer (NSCLC) with HER2 exon 20 insertion mutations, received a complete response letter (CRL) from the US FDA. The CRL cited insufficient trial data and suggested that a randomized controlled trial would be necessary to secure approval.
Partnership and Development
Spectrum is the US partner for poziotinib’s originator, South Korea-based Hanmi Pharmaceutical Co., Ltd (KRX: 128940), under a 2015 license deal. In China, the rights to the drug are held by Luye Pharma Group Ltd (HKG: 2186) following a USD 20 million license agreement in 2014. Luye and Hanmi initiated a Phase II trial for poziotinib in China in 2019, according to data from clinicaltrials.gov.
Clinical Trial Data
Spectrum was seeking accelerated approval for poziotinib based on data from the Phase II single-arm ZENITH20 trial (NCT03318939), which recruited over 600 patients across the United States and Europe. The drug was administered as a once-daily dose of 16 mg, achieving an objective response rate (ORR) of 27.8% (95% CI, 18.9%-38.2%), a median duration of response (DOR) of 5.1 months (95% CI, 4.2-5.5), and a median progression-free survival (PFS) of 5.5 months (95% CI, 3.9-5.8).
Company Response
The CRL was anticipated after the FDA’s Oncology Drugs Advisory Committee (ODAC) voted 9-4 against recommending poziotinib in September, citing safety concerns and insufficient efficacy benefits. In response, Spectrum stated it would “immediately deprioritize the poziotinib program,” including a 75% reduction in R&D staff. The company will instead focus on the commercialization of Rolvedon (eflapegrastim), another drug licensed from Hanmi that was approved to treat chemotherapy-induced neutropenia in September and is viewed as a potential USD 2 billion drug.-Fineline Info & Tech
