In another swift, early-to-market move,Bristol-Myers Squibb Co.’s Opdivo has become the first checkpoint immunotherapy to secure FDA approval in kidney cancer.

The agency approved Bristol’s PD-1 inhibitor Opdivo (nivolumab) on Nov. 23 for advanced renal cell carcinoma, after prior treatment with angiogenic therapy.

The approval came only a week after Bristol announced FDA had accepted the sBLA for priority review, which also had breakthrough status, setting a March 16, 2016 user fee date. From the mid-September submission, the agency cleared the supplemental indication in about nine weeks.

The agency is well-acquainted with the drug, which has had four approvals in the past 16 months. Its previous approvals as a single agent have all also significantly ahead of the user fee deadlines, the longest at five months, but the latest is the fastest.

Another Sign Of Bristol's Lead In Immuno-Oncology

With the members of the PD-1/L1 family looking so similar, sponsors need to differentiate their products on grounds other than a molecule’s particular characteristics – and one important way of doing so is getting to the market first.

Bristol introduced the first checkpoint inhibitor to the market, the CTLA-4 inhibitor Yervoy (ipilimumab) in March 2011. Opdivo was approved first in Japan, but Merck’s Keytruda cut Opdivo in line to win the first US PD-1 approval in September 2014, albeit launching without overall survival data. Following approval in December 2014 for melanoma, with overall survival data, Opdivo became the first PD-1 inhibitor approved for non-small cell lung cancer, for the squamous type, in March 2015 and quickly overtook Keytruda sales ([A#00150803019]). The drug trailed slightly behind Keytruda for non-squamous NSCLC but emerged with a broader label, for use regardless of PD-L1 expression, upon approval in early October, well ahead of a Jan. 2 user fee date ([A#14151009003]).

Bristol also claimed the first approval of a combination of cancer immunotherapies, with the September clearance of Yervoy and Opdivo for front-line melanoma, and Yervoy was cleared for adjuvant treatment of melanoma, the first approval of a checkpoint immunotherapy in that setting ([A#00150105011]).

Opdivo brought in $305m in the third quarter and a new indication promises to further enhance sales ([A#14151027011]).

All of the sponsors of checkpoint inhibitors have been looking to expand use into multiple tumor types and kidney cancer has been one of the earliest targets because, like melanoma, it has been known to respond to immunotherapy approaches. However, the kidney cancer market opportunity in and of itself is expected to be modest relative to other tumor types. In a bullish immuno-oncology report in 2015, Morningstar Research analyst Damien Conover estimated the indication will account for only $2bn out of a total $33bn in 2022, and that Bristol would take a 60% share in kidney cancer.

Merck’s anti-PD-1 Keytruda (pembrolizumab), which is approved for melanoma and lung cancer, is in Phase I/II for renal carcinoma. Roche’s PD-L1 inhibitor atezolizumab is in Phase III for renal cancer and is expected to be submitted soon for lung and bladder cancers.

Entering The Market With Survival Advantage

Opdivo and Pfizer Inc.’s Torisel (temsirolimus) are the only FDA-approved therapies proven to improve overall survival, FDA’s Richard Pazdur, director of the Office of Hematology and Oncology Products, said in a statement announcing the approval.

The filing was supported by a Phase III study of 821 patients with advanced renal cell carcinoma who had failed treatment with an angiogenic agent. Overall survival for those on Opdivo was 25 months versus 19.6 months for a comparator arm on Novartis AG’s Afinitor (everolimus).

“This effect was observed regardless of the PD-L1 expression level of patients’ renal cell tumors,” FDA noted.

The objective response rate with Opdivo was also much better at 21.5% vs. 3.9%.

Bristol Gets First Mover-Advantage, Again, With Opdivo Kidney Cancer Approval

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