- Members of a Food and Drug Administration panel were split on Tuesday about whether a Pfizer Inc. cancer medication should gain approval for a new indication.
- The Oncologic Drugs Advisory Committee voted six in favor and six against Sutent's risk-benefit profile as an adjuvant treatment for adults with renal cell carcinoma (RCC) who are at high risk of their cancer returning after nephrectomy. The votes hinged on data from the Phase 3 S-TRAC study.
- In that clinical program, adjuvant Sutent significantly outperformed placebo in improving disease-free survival (DFS) for patients at high risk of recurrent kidney cancer after surgery. Yet, the drug — first approved in advanced RCC more than a decade ago — also carries with it a black box warning for liver toxicity.
Sutent (sunitinib) remains a strong source of income for Pfizer. The drug hit blockbuster status in 2016, just as it had each year since 2010. While such a track record would suggest the franchise is in its prime, there are some concerns.
The basic patents protecting the drug from generic competition in the U.S. and Europe, for example, run out in 2021. What's more, the FDA has approved a growing pile of treatments for kidney cancer since Sutent originally came to market, including Bristol-Myers Squibb Co.'s closely watched PD-1 inhibitor Opdivo (nivolumab) and Roche AG's powerhouse oncology offering Avastin (bevacizumab).
Pfizer blamed a relatively stagnant second quarter performance by Sutent on "competitive pressure in the U.S. and Europe and cost containment measures in certain developed international markets," in its most recent 10-Q filing. Revenue from the drug totaled $279 million during the quarter, down ever so slightly from the $285 million recorded for the same period in 2016.
A new indication, therefore, could buttress Sutent against market and exclusivity pressures.
Pfizer has focused its sights on the adjuvant setting for RCC. The company claims that up to 80% of clear cell RCC patients will have a nephrectomy or some kind of surgery to remove their tumors. Additionally, of the 15% of primary resected RCC patients deemed high-risk, about 60% will have their cancer come back and metastisize within five years of treatment, according to Pfizer.
Results from the S-TRAC trial showed that, following surgery and a year of treatment, high-risk RCC patients who took Sutent lived on average 6.8 years before their cancer came back, versus 5.6 years for those on placebo. While the trial's experimental arm had a 24% overall risk reduction compared to the control arm, it also had more instances of severe or life-threatening adverse events. Investigators noted grade 3 or higher adverse events in 63.4% of patients on Sutent and 21.7% of patients on placebo.
The dichotomy between Sutent's efficacy and safety surely contributed to the advisory committee's split vote.
The panel's central questions about Sutent all related to S-TRAC: whether treatment actually improved DFS, whether DFS was even the best endpoint to use, and whether the trial's results aligned with other studies evaluating the drug in the adjuvant RCC setting. Notably, Sutent failed to significantly improve DFS compared to placebo or sorafenib (the active ingredient in Bayer AG's Nexavar) in the Phase 3 ASSURE investigation.
It's uncertain how the panel's vote will affect the FDA's approval decision for Sutent in this new indication. Though the agency typically follows suit with advisory committee recommendations, a tie vote means there isn't a clear message being sent.
"We are encouraged by today’s productive discussion and look forward to working with the FDA over the next few weeks as they incorporate today’s discussion into their review and decision regarding SUTENT in this patient population," Mace Rothenberg, chief development officer of oncology for Pfizer's global product development unit, said in a Sept. 19 statement. "Sutent has long been a standard of care for the treatment of advanced RCC and we believe that this potential benefit can be extended into patients with high-risk of RCC recurrence, as demonstrated in the S-TRAC trial."
Pfizer filed an abbreviated New Drug Application for Sutent in May. The drug has a target action date scheduled for January.