Despite the challenges of being a biologic pioneer, Amgen Inc.'s melanoma drug, talimogene laherparepvec, or T-vec, garnered the support of two FDA advisory committees – with some caveats.

The Cellular, Tissue and Gene Therapies and Oncologic Drugs Advisory Committees voted 22-1 Wednesday that T-vec's overall risk-benefit profile supported traditional approval for the treatment of injectable, regionally or distantly metastatic melanoma.

It was the wording of the indication for the first-in-class oncolytic immunotherapy that drew the lone no vote and several of the caveats.

The data were clear, but the FDA's question was muddy, said Richard Sherry, a staff clinician at the National Cancer Institute. His concern was the broadness of the patient population represented in the indication when the data showed T-vec had the most significant effect in stage III and IVa melanoma.

"This is a chance to make a statement," he said. "This drug is not appropriate for the vast majority of patients with visceral disease."

Patrick Hwu, a melanoma professor at the University of Texas M.D. Anderson Cancer Center, supported approval without limiting the patient population. "I need as many arrows as possible in my quiver" to better treat patients, he said, noting that T-vec is among the least toxic cancer agents.

While he wouldn't use it blindly on patients, Hwu said he has patients he would treat with the drug. "Let physicians be professionals and make the best decisions" for their patients, he added.

Sherry shot back that no one outside the FDA and advisory committees will look at the clinical trial data to see which patients truly benefitted from T-vec.

While several other panelists agreed with Sherry that T-vec should be restricted to melanoma patients without visceral disease, they voted yes on approval. However, they recommended labeling restrictions and education programs for oncologists and patients.

Like Hwu, panelist Louis Diehl, a professor at Duke University Medical Center, voted an unequivocal yes, saying the patient testimony during a public hearing helped him focus on the benefit of the drug. Given how T-vec saved the patients' lives when their doctors had given up hope, he said he wouldn't want to take the drug out of the hands of oncologists or restrict its use to certain patient subgroups.

If approved, T-vec would be only the second therapeutic cancer vaccine approved by the FDA and the first approved to treat melanoma. But for panelist Grzegorz Nowakowski, an assistant professor at Mayo Clinic, the drug is just another modality in the oncologist toolbox. As a single agent, he doesn't think it will change the melanoma field, which has seen the approval of a number of new therapies since the phase III T-vec trial started in 2008.

Going forward, Hwu said, Amgen needs to look at T-vec in combinations, especially with some of the newer melanoma drugs.

In the briefing documents released before the adcom meeting, the FDA struck a critical tone, noting that T-vec showed a "strong trend" but missed statistical significance in overall survival (OS) in the phase III study in metastatic melanoma. Although OS was a secondary endpoint and T-vec met the primary endpoint of durable response rate in the randomized, open-label OPTiM trial, the FDA's penchant for a strong OS benefit is well known in the cancer community. (See BioWorld Today, April 28, 2015.)

Since T-vec is derived from an attenuated herpes simplex virus-1 isolate, the FDA also raised concerns about the potential for viral shedding and transmission. While the committees spent considerable time discussing the possibility, the panelists didn't seem overly concerned, describing it as low risk. Amgen is conducting a shedding study to shed more light on the issue.

The Thousand Oaks, Calif.-based company acquired T-vec, then known as Oncovex, in its $1 billion buyout in 2011 of Biovex Group Inc. (See BioWorld Today, March 21, 2013.)