Bristol Myers celebrates 10 years of Opdivo with FDA approval for subcutaneous version

Almost exactly 10 years after the FDA’s initial FDA approval for Bristol Myers Squibb’s Opdivo as the first PD-1 inhibitor in the U.S., the agency has cleared an under-the-skin version of the cancer immunotherapy.

The Dec. 27 approval was granted to Opdivo Qvantig, which co-formulates nivolumab with recombinant human hyaluronidase, in nearly all existing solid tumor indications for intravenous Opdivo. Hyaluronidase is an enzyme that facilitates subcutaneous absorption of the active drug nivolumab.

The subcutaneous version could transform the way care is delivered to patients, as it allows providers to spend less time preparing and administering treatment, Wendy Short Bartie, Bristol Myers’ senior VP of U.S. oncology & hematology commercialization, said in an interview with Fierce Pharma ahead of the approval.

For healthcare facilities, Opdivo Qvantig could reduce burdens related to infusion capacity; for patients, it cuts the treatment time for receiving a checkpoint inhibitor from a 30-minute infusion to three to five minutes for an injection, Bartie said.

Before BMS’ offering, Roche’s PD-L1 inhibitor Tecentriq became the first checkpoint inhibitor to secure a subcutaneous approval from the FDA. Called Tecentriq Hybreza, the injection’s treatment time is about seven minutes. The two rivaling PD-1/L1 drugs both incorporate Halozyme’s recombinant human hyaluronidase-based subcutaneous drug delivery technology, ENHANZE.

Opdivo Qvantig’s average administration time of less than five minutes was observed in the Checkmate-67T trial, which was conducted among patients with kidney cancer. In the study, the subcutaneous formulation matched up to the IV on both co-primary pharmacokinetics endpoints as well as the key secondary endpoint of tumor response rate, with that measure favoring Opdivo Qvantig.

In one notable difference compared with IV Opdivo, the FDA-approved label for Opdivo Qvantig does not allow the subcutaneous drug to be used in combination with BMS’ CTLA-4 inhibitor Yervoy, which presents as an IV.

As a result, in combination indications in kidney cancer and advanced melanoma, where Opdivo treatment lasts longer than its therapeutic partner, the subcutaneous version can only be given after Yervoy dosing is concluded. For original Opdivo-Yervoy indications in first-line non-small cell lung cancer and esophageal squamous cell carcinoma, where the two immunotherapies are given together throughout treatment, use of Opdivo Qvantig is completely restricted.

BMS is “exploring opportunities to generate data” on Opdivo Qvantig and Yervoy combination therapy in NSCLC “to determine an appropriate dose that will ensure consistent efficacy and safety,” a company spokesperson told Fierce Pharma.

BMS expects Opdivo Qvantig will be a welcome addition in both academic and community treatment settings, Bartie said. Initial adoption is expected within monotherapy indications as well as combinations with oral meds, whereas utilization in regimens that involve other IV drugs may come later, she said.

The BMS exec specifically highlighted Opdivo’s use a perioperative treatment in early-stage NSCLC. Approved by the FDA in October, the indication allows Opdivo first to be used with chemotherapy—which comes as an IV—before surgery, and then as a monotherapy after surgery.

For the monotherapy maintenance period, the option of a subcutaneous drug is “incredibly attractive,” Bartie said.

In addition, kidney cancer serves as another area where patients could quickly begin utilizing Opdivo Qvantig. In that disease, Opdivo is approved alongside Exelixis’ oral tablet Cabometyx as a first-line treatment.

By BMS’ projection, about 30% to 40% of all Opdivo-eligible patients in the U.S. will eventually convert from the IV to the subcutaneous formulation.

As to whether Opdivo Qvantig can expand the patient population base for Opdivo, Bartie suggested that the drug’s growth will still mainly come from some key tumor types and potential new indications. She described the new offering as the “proverbial icing on the cake” that allows physicians a more efficient and easier route of administration. Nevertheless, the easier-to-administer trait may help Opdivo Qvantig reach certain community practices that have so far not used immunotherapy very much, she added.

With their own patent protection, subcutaneous delivery systems are considered a meaningful way to extend the sales runway of members of the blockbuster PD-1/L1 class. Besides BMS and Roche, Merck & Co. is not so far behind in this pursuit. The PD-1 leader in November touted a positive pivotal trial readout for its subcutaneous formulation of Keytruda, with regulatory filings underway in solid tumors.  

Besides Opdivo, BMS is working to turn its PD-1/LAG-3 fixed-dose combination of nivolumab and relatlimab into a subcutaneous therapy through the Relativity-127 trial.