Back in 2018, Bristol Myers Squibb’s Opdivo grabbed bragging rights as the first PD-1/L1 agent to land an FDA nod in small cell lung cancer. Fast forward to the end of 2020, and that indication is no more.
The New York pharma acknowledged defeat last week, withdrawing Opdivo's indication in SCLC that has progressed after platinum-base chemo and at least on other line of therapy.
The development came two years after the failure of two confirmatory studies, which were meant to turn Opdivo’s accelerated approval—earned in 2018—into a full one.
The original conditional nod was based on data from a phase 1/2 trial that showed a 12% response rate for the PD-1 inhibitor, with the effect lasting a median 17.9 months. But merely two months after that regulatory win, the phase 3 CheckMate-331 study found Opdivo wasn’t better than chemotherapy at extending patients’ lives in those who had failed on one round of platinum chemo.
The drug stumbled again a month later—this time in combination with its fellow checkpoint inhibitor Yervoy. At the time of the CheckMate-451 flop, industry watchers were skeptical that Bristol Myers could keep its approval.
As BMS pointed out, the SCLC treatment landscape has changed a lot since its 2018 approval, with the availability of more options across multiple lines of therapy.
Merck & Co.’s Keytruda landed the same third-line SCLC accelerated approval in June 2019 based on tumor shrinkage data. But then the pairing of Keytruda and chemotherapy failed to top solo chemo at helping patients live longer in newly diagnosed, extensive-stage SCLC in the phase 3 Keynote-604 trial.
By contrast, Roche’s Tecentriq, used in tandem with chemotherapy, was approved in the first-line SCLC setting after showing a 30% reduction in the risk of death over solo chemo. And AstraZeneca’s rival PD-L1 Imfinzi followed into the field last March with a 27% improvement for its chemo combo.
The FDA’s accelerated approval is designed to bring innovative drugs for serious conditions to the market faster based on surrogate trial endpoints. Drugs approved under this pathway are required to prove their benefits in confirmatory trials.
However, the agency seldom takes action after confirmatory trial failures. For example, Roche got to keep its Tecentriq approval in previously untreated bladder cancer patients ineligible for cisplatin chemo or patients who’ve had previous platinum therapy despite the IMVigor-211 letdown.
But in some cases—like Bristol Myers' with Opdivo in SCLC—a drugmaker may see no point in further marketing a failed drug even if the FDA doesn't make a move itself. In 2019, Eli Lilly pulled Lartruvo from the market for the treatment of advanced soft tissue sarcoma following the failure of the phase 3 Announce trial.