Written by Michael Ehrman

(Reuters) – US drugmaker Merck & Co hopes to secure a patent for a new $20 billion formulation of the cancer immunotherapy Keytruda that can be injected under the skin, allowing it to shield the best-selling drug from expected competition by 2028.

For many years, Merck has relied on Keytruda to fuel its growth. The treatment, which was approved in 2014, harnesses the body’s immune system to fight cancers with dramatic results. Against advanced lung cancer, it has resulted in a five-year survival rate in about a quarter of people compared to 5% of people historically.

But key patents on Keytruda will begin expiring in 2028, opening the door to biosimilars — near copies of expensive biological drugs whose complex molecules implanted inside living cells make it impossible to manufacture identical copies.

Merck is testing in clinical trials two versions of the drug that can be injected under the skin, a rapid-fire alternative to an injection, the current delivery method in which patients receive an injection into a vein at a health office once every three or six weeks. The company reported early data from one of those trials last year.

While Merck has revealed that it is developing subcutaneous versions of Keytruda, it has not previously said that it expects the new formulation to become the most widely used version of the drug after its introduction and a driver of growth towards the end of the decade. .

If successful, a senior Merck executive told Reuters, Merck could begin marketing the new formulation within a few years. It expects it to fuel Keytruda’s growth as it gains approvals in early-stage cancers. Keytruda now accounts for more than a third of Merck’s sales.

Merck’s chief financial officer, Caroline Lichfield, said in an interview, using terminology for standards under US law determining patentable technologies.

“The hands of that patent will start ticking from the time we get this patent.”

Eliav Bar, Merck’s chief medical officer, told Reuters that while some patients were more likely to receive the original formulation if it was given along with chemotherapy or other intravenous drugs, the subcutaneous formulation can replace the intravenous version for most patients.

“Theoretically it could replace everywhere you currently use Keytruda,” Barr said.

Drug patents have a guaranteed exclusivity of 20 years after a patent is obtained under US law, but sometimes companies are able to add additional patents that extend their exclusivity.

For example, the initial patent for Abbvie’s arthritis drug Humira expired in 2016, but the drug won’t face US competition until 2023, in part because the company ultimately received more than 130 patents protecting the drug.

Merck’s patents on the subcutaneous version of Keytruda could protect that formulation until at least 2040, according to Tahir Amin, co-founder of the drug patent monitoring group, the Medicines, Access and Knowledge (I-MAK) initiative.

“It’s the way drug companies now use this system — it’s all about taking up as much space as possible, making it difficult for anyone to get in,” Amin said. “Ketruda will be the next Humira by all accounts.”

Asked if it was motivated more by patent issues than by medical need, Merck said it is constantly focused on improving Keytruda and getting it to more patients.

Merck said it may seek patents for innovations in how the drug is used, its formulation, size and dosing schedule and combinations with other drugs.

“These patent applications, if granted, may provide varying degrees of protection after 2028. However, we will continue to point to late 2028 as the most likely time frame for biosimilars to enter the market,” Merck said in a statement.

Do patients prefer the shots?

Convincing doctors and hospitals to adopt the new formula before biosimilar competition arrives could help Merck protect more Keytruda revenue for longer, analysts said, but this is uncertain. On average, they expect Keytruda’s revenue to reach $30 billion in 2026 and $35 billion by 2028, according to Refinitiv data.

“Theoretically, in the US, they can convert all of the market, depending on how quickly they can bring it to market,” said Mizuho analyst Mara Goldstein.

However, BMO Capital’s Evan Seigerman said private insurers in the US may refuse to pay for the more expensive brand-name product and prefer the biosimilar infusion version. However, he believes the new formula could allow the company to keep up to 20 percent of Keytruda’s revenue in the 2030s.

Two physicians interviewed by Reuters said they were not convinced that the new route of administration represented a significant enough clinical improvement over intravenous infusions to justify the additional systemwide health care costs that might be the result of Merck’s new patent.

“I don’t think it will improve the safety or efficacy of the drug,” said Dr. Shailender Bhatia, an oncologist at Fred Hutchinson Cancer Center in Seattle.

Merck’s Barr said the drug’s easier-to-use formulation could help patients’ health by keeping them on Keytruda and on schedule, and could prevent high-risk cancer patients from spending long times in hospital settings where they could be exposed to other ailments.

“From a quality-of-life perspective and from a patient perspective, this would definitely be beneficial,” Barr said.

This view is supported by clinical studies which have found that patients prefer subcutaneous injections over intravenous injections which can be time consuming and invasive.

The extent to which hospitals and clinicians adopt this method can reflect how they will be affected financially by the change.

Hospitals are usually paid less than long-term intravenous injections. This could be offset to some extent if the drug’s price was higher, since providers receive a fee for a percentage of the drugs a doctor administers, according to Lisa Molloy, chief pharmacy officer at Northwell Health Hospital System in New York.

Merck said it would not speculate on the expected price of the pipeline products. The list price for an infusion is about $185,000 a year, though the drug may cost less with company discounts.

Transferring patients to subcutaneous drugs also opens up spots in injection centers for additional patients, Molloy said of Northwell.