The FDA has approved Merck & Co.’s under-the-skin version of Keytruda, reducing treatment time burden for patients while granting the world’s bestselling drug potential blockbuster revenue protection.
Friday’s approval for Merck’s Keytruda Qlex covers the solid tumor indications approved for the original intravenous formulation of Keytruda, according to the FDA.
With $8 billion in sales for the second quarter, Keytruda accounted for more than half of Merck’s total revenue during the period. As infused Keytruda is slated to lose patent protection in 2028, the subcutaneous formulation will be critical to the New Jersey pharma’s top-line stability.
For patients and doctors, Keytruda Qlex promises the benefit of convenience and reduced time spent during treatment, all with the same level of efficacy.
The infusion time for Keytruda is a little over half an hour, whereas the injection of Keytruda Qlex takes about one minute every three weeks, or two minutes for every six weeks, depending on the regimen.
“Just that time component and being able to give that back is really valuable for patients,” Marjorie Green, M.D., Merck’s head of oncology global clinical development, said in an interview with Fierce Pharma ahead of the FDA’s decision.
It also reduces the burden on healthcare providers and health systems because of the shorter preparation and administration time, she explained.
The treatment effect of Keytruda Qlex was proven in the MK-3475A-D77 study. Among patients with treatment-naïve metastatic non-small cell lung cancer (NSCLC), Keytruda Qlex showed similar body exposure compared to intravenous Keytruda in their respective combinations with chemotherapy. Besides comparable blood concentrations as measured by two primary pharmacokinetic endpoints, the two versions also showed no notable differences on efficacy outcome measures such as tumor response rate, progression-free survival or overall survival.
While the test was conducted in NSCLC, the FDA approval includes existing solid tumor indications for Keytruda. Merck is running a separate pivotal study in previously treated Hodgkin lymphoma and primary mediastinal large B-cell lymphoma in the hopes of covering Keytruda’s blood cancer indications.
Merck expects to switch 30% to 40% of Keytruda uses to the subcutaneous version in about 18 months to two years. The company expects the majority of adoptions to be in settings where Keytruda is used by itself or with an oral drug.
Keytruda has expanded into the treatment of several early-stage cancers, where it’s given as monotherapy following surgical removal of tumor tissues. Besides the adjuvant setting, Green also sees potential adoption for Keytruda Qlex in certain metastatic cancer indications, especially in cases where the use of chemotherapy infusions is confined to a short period.
Some of Merck’s new clinical trials will also start to incorporate the subcutaneous version. Green raised the example of a combination with the company’s oral KRAS inhibitor, MK-1084, in first-line NSCLC.
Before Keytruda Qlex, the FDA had already approved subcutaneous versions of its immunotherapy rivals: Roche’s Tecentriq and Bristol Myers Squibb’s Opdivo.
From an external competition perspective, Green argued that Keytruda Qlex can maintain the success of Keytruda, given that it has shown consistent efficacy while boasting the shortest administration time in the field.
Merck plans to launch Keytruda Qlex soon despite ongoing patent litigation with Halozyme Therapeutics around the human hyaluronidase protein that enables the drug’s subcutaneous delivery. The Merck product utilizes Alteogen’s berahyaluronidase alfa, which Halozyme alleges infringes its broad portfolio of modified hyaluronidase patents called Mdase. The U.S. Patent and Trademark Office has issued a post-grant review for a Merck challenge to some of Halozyme’s patents.
Given Merck’s heavy reliance on its top-selling PD-1 inhibitor, Keytruda Qlex has been tasked to ameliorate the expected Keytruda erosion beginning in 2029.
With Keytruda’s looming patent expiration and a lackluster performance of the HPV vaccine Gardasil, Merck has recently launched a sweeping cost-cutting initiative designed to save the company $3 billion per year by the end of 2027. Under that program, Merck will cut about 6,000 jobs, or 8% of its global workforce.