With biosimilar competition heading toward Keytruda, Merck & Co.  on Tuesday launched a subcutaneous version of the flagship cancer medication that analysts believe will significantly offset a looming patent expiration.

Delivered under the skin in one or two minutes — as opposed to a half-hour infusion — Keytruda Qlex is expected to gain traction quickly, although not nearly as fast as the original’s pending decline. Qlex has been approved for 38 of the solid tumor indications addressed by the original.

The best-selling drug in the world, Keytruda pulled in almost $29.5 billion last year, representing almost half of Merck’s total sales. According to market intelligence firm Evaluate, annual sales are slated to peak at almost $32.7 billion in 2026.

But the downhill slide should start in 2027. After a shallow impact at first, the average analyst forecast has sales dwindling to just over $7 billion by 2032.

Qlex, though, should be running by then too. Analysts forecast sales will rise steadily and hit more than $7 billion that year. While the total for the two versions likely won’t match the original’s massive peak at that point, proceeds from the subcutaneous shot will soften the blow for Merck, said Alicia Heesen, advisory services consultant at Managed Markets Insight and Technology.

“This is an obvious game changer,” Heesen said. 

Factoring in Qlex, the anticipated revenue for 2028 and 2029 “doesn’t even look like a sharp decline anymore,” she added. “This will extend their market share and increase potential revenue over the next five years post-loss of exclusivity.”

On top of its sales potential, the shot is a “significant improvement for patients,” said Cathy Pietanza, vice president of global clinical development at Merck Research Laboratories.

“I’ve seen patients wait long hours in the infusion clinic or days for an appointment,” Pietanza said. “Keytruda Qlex provides a big advancement in cancer care because it gives patients their time back and it decreases the burden on the healthcare system.”

A yearslong journey

First approved for melanoma in 2014, Keytruda proved a force to be reckoned with across tumor types and went on to secure approvals for dozens of new indications. 

Merck’s effort to develop a subcutaneous version began before Pietanza joined the company in 2019. While results ultimately showed the pharmacokinetic availability of the drug, Merck had something else in mind to make Qlex even better.

The company partnered with South Korea’s Alteogen in 2020, securing access to hyaluronidase, an enzyme designed to allow large-volume subcutaneous administration of biologic drugs like Keytruda. The new delivery technology gave Merck the option to administer the injection every three or six weeks with one vial per dose rather than two pre-filled syringes, Pietanza said.

Bristol Myers Squibb’s Opdivo and Roche’s Tecentriq, both fellow immunotherapies that work similarly, have received subcutaneous approvals. But Keytruda Qlex is likely to have the biggest footprint due to the outsized success of its original concoction.
 
The goal of Merck’s phase 3 pivotal study of Keytruda Qlex was non-inferiority to the original version of the drug, and the subcutaneous shot had a 45% overall response rate in non-small cell lung cancer while the original Keytruda showed 42%.

The study was accompanied by a “switching trial” designed to determine patient preference, where patients began with one version or the other, switched halfway, and then afterward chose which version to continue, said J. Thaddeus Beck, oncologist and medical director of the Highlands Oncology clinical trials office in Arkansas.

Patients preferred the subcutaneous form, Beck said. And while Qlex significantly alters the patient experience, it’s also changing the physical layout of Highlands’ infusion center, he said.

“We’re remodeling offices and changing the way we design and approach new construction to create a whole section specifically for subcutaneous administration,” Beck said. “Sort of a fast track part of the infusion center.”

The payer factor

Merck expects about 30% to 40% of patients to make the switch from IV to subcutaneous based on patient profiles and availability, Heesen said. That’s because about 60% to 70% of Keytruda-treated patients use the medicine in combination with another IV drug, which would make the transition unnecessary, she added.

But that’s enough to draw patients into a regimen that requires just one or two minutes of therapy, making them unlikely to want to go back to a 30-minute IV made available by biosimilars. The switch is sensible for payers, as well, Heesen argues.

“Payers aren’t going to want to start paying hospitals for the chair time when a minutes-long regimen is available,” she said.

Merck has said it will price Qlex at parity with Keytruda, which is listed at about $12,000 for a 3-week course.

A report provided via email by MMIT found that a quarter of payers “are likely to prefer the new subcutaneous version over the existing IV version due to its cost efficiency, ease of use and variety in site of care options.”