Another checkpoint inhibitor has entered the fray, as Checkpoint Therapeutics has passed the FDA’s checkpoint with its PD-L1 inhibitor cosibelimab.
The FDA has approved cosibelimab under the brand name Unloxcyt for the treatment of metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC that’s not curable by surgery or radiation, the agency announced Friday.
While Unloxcyt is the first PD-L1 inhibitor approved to treat CSCC, PD-1 inhibitors such as Regeneron’s Libtayo and Merck & Co.’s Keytruda are already available in the indication.
Unloxcyt’s approval was backed by tumor shrinkage data from a study coded CK-301-101. Among 78 patients with metastatic CSCC, Unloxcyt registered a 47% response rate by independent central review. Among 31 patients with locally advanced disease, the response rate was 48%.
The median duration of response was not reached in the metastatic group and was 17.7 months in the locally advanced cohort. Among patients who responded, 54% experienced responses of at least 12 months in the metastatic group, compared with 20% in the locally advanced group.
Depending on the metric being assessed, Unloxcyt’s results show stronger or weaker points compared with Keytruda’s or Libtayo’s data from their own trials. While cross-trial comparisons carry inherent flaws, Libtayo’s label shows that the first PD-1 therapy approved for CSCC had 77% of responders still in remission for at least a year in a combined CSCC cohort encompassing both metastatic and locally advanced patients.
For Keytruda, the Merck behemoth’s 35% overall response rate in the metastatic CSCC setting was below Unloxcyt’s showing. But Keytruda’s 47.2-month median duration of response in the locally advanced cohort appeared markedly better than Unloxcyt’s.
Differences observed from these cross-trial comparisons don’t bear much significance as baseline patient characteristics and patient follow-up times are different. In a longer follow-up (PDF) of study CK-301-101 shared in September, Unloxcyt’s estimated 12-month duration of response probability shot up to 75.4% and 88.2% in metastatic and locally advanced patients, respectively.
The FDA’s approval for Unloxcyt has vaulted Checkpoint Therapeutics to the commercial stage. The Massachusetts biotech had to wait an extra year and work out a complete response letter related to issues at a contract manufacturer to reach this milestone.
“This approval marks Checkpoint’s transformation to a commercial-stage company, with the opportunity to compete in a U.S. market estimated to exceed $1 billion annually,” the company’s CEO, James Oliviero, said in a statement Friday.
CSCC is the second most common form of skin cancer in the U.S., with about 40,000 new diagnoses of advanced cases each year, according to Checkpoint.
Oliviero argued that Unloxcyt offers a new option by binding to PD-L1 rather than PD-1, and that its demonstrated ability to induce antibody-dependent cell-mediated cytotoxicity is another potential differentiating factor versus existing therapies. However, neither mechanistic feature seems to have translated into a meaningful clinical efficacy advantage.
Without a clear differentiator from those incumbents, Unloxcyt might have a difficult time winning share as a PD-1/L1 latecomer. Just consider Coherus BioSciences’ Junshi Biosciences-partnered Loqtorzi. In October 2023, the PD-1 inhibitor became the first FDA-approved agent for recurrent or metastatic nasopharyngeal carcinoma. In the third quarter of this year, Loqtorzi’s net sales came in at just $5.8 million.
Checkpoint intends to commercialize Unloxcyt “through one or more potential partnerships or other type of corporate development transaction to enable a potential launch in 2025,” a media aide told Fierce Pharma.
The company won’t share Unloxcyt’s price for now but said it “may be set at or near parity with other approved anti-PD-(L)1 therapies.”
Elsewhere, Checkpoint plans to submit applications to the European Medicines Agency and the U.K.’s Medicines and Healthcare Products Regulatory Agency as soon as possible, perhaps “through a potential partner with an established commercial infrastructure in Europe,” the media aide said.