FDA advisory committee votes down Spectrum's lung cancer hopeful in wake of efficacy concerns

After an almost yearlong wait, Spectrum Pharmaceuticals has received a pretty clear hint about whether the FDA will approve its lung cancer drug. Unfortunately, it's unlikely to be the answer the company wants.

The FDA's Oncologic Drugs Advisory Committee (ODAC) met Thursday to review Spectrum's oral tyrosine kinase inhibitor Pozenveo, also called poziotinib, for patients with previously treated locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring the human epidermal growth factor receptor exon 20 insertion mutation.

The committee—an independent panel of experts that advises the FDA on product approvals but doesn’t dictate final decisions—voted 9-4 that Pozenveo’s benefits don’t outweigh its risks. The FDA's thinking was made clear in a document released ahead of the committee's meeting, which cited concerns regarding dosing and efficacy.

“If granted accelerated approval, this would be the least effective targeted therapy for lung cancer approved to date,” the document reads.

The FDA pointed to Pozenveo’s objective response rate (ORR) of 28% and median duration of response (mDOR) of 5.1 months in a confirmatory trial. The agency compared this to Daiichi Sankyo and AstraZeneca's Enhertu, which the FDA approved for the same indication last month after demonstrating a 58% ORR and 8.7 month mDOR.

The agency also cited Pozenveo’s “poorly tolerated safety profile,” as 57% of patients had to undergo dose reductions and 85% experienced severe or life-threatening side effects. Spectrum’s stock dropped by 38% over the course of Tuesday, the day the document was released, with trading halted altogether on Thursday.

“We are disappointed by the outcome of the ODAC meeting, as patients with NSCLC HER2 exon 20 insertion mutations are in need of additional effective and safe therapies,” Spectrum CEO Tom Riga said in a Sept. 22 release. “We plan to carefully evaluate our options for this program as we approach the November 24, 2022, PDUFA date.”

The rejection comes after Spectrum scored its first FDA approval earlier this month in the form of Rolvedon, an injection that reduces the incidence of infection tied to neutropenia in cancer patients receiving chemotherapy. 

Despite the success, Spectrum isn’t new to FDA rejections. Rolvedon, previously known as Rolontis, was knocked back by the agency last year due to manufacturing deficiencies. This January, the company cut 30% of its staff and reorganized its pipeline to focus on Rolantis and Pozenveo at the expense of its early-stage pipeline.