With a patent expiration still 4 years off, biosimilar makers are positioning themselves for a new biologic drug category, which may represent a greater opportunity than even adalimumab. Pembrolizumab (reference drug Keytruda®, manufactured by Merck) looms on the horizon, tantalizing the biosimilar community within a new oncology category.
Pembrolizumab is the 800-pound gorilla of the PD-1 inhibitor class of oncology biologics. PD-1 stands for the programmed cell death-1 receptor. The molecule prevents the interaction between the receptor and its ligand PD-L1, which then allows the body’s own cellular anti-tumor system to identify and kill tumor cells. Keytruda is indicated for the treatment of a multitude of tumors, including melanoma, non-small cell lung cancer (NSCLC), head and neck squamous-cell cancer, classical Hodgkin lymphoma, urothelial carcinoma, esophageal cancer, hepatocellular cancer, biliary tract cancer, renal-cell cancer, gastric cancer, cervical cancer, and well the list goes on. You get the idea that PD-1 inhibition is an extremely useful tool for oncologists. So much so, that Merck’s 2023 US sales revenues for Keytruda were $15.1 billion (a 19% increase over 2022 US sales) and some $25 billion worldwide. One estimate of annual sales by the 2028 Keytruda patent expiration is $34 billion. Interestingly, Merck’s main PD-1 competitor, Bristol Myers Squibb’s Opdivo®, is also set to lose patent protection in 2028, but it presently accounted for “only” $5.3 billion in US sales in 2023.
It is too early to guess who is leading the race to approve the first pembrolizumab biosimilar. However, a couple of major biosimilar developers are vying for pole position, based on their clinical trial progress.
Samsung Bioepis SB27. The company announced that the phase 3 clinical trial of SB27 was initiated in March (according to the listing for NCT06348199). The noninferiority study against Keytruda is a double-blind, multicenter study in over 600 patients with metastatic NSCLC. The estimated date for primary study completion is in September 2025. Assuming a positive result, a 351(k) filing may be possible in Q1-Q2 2026, with approval ahead of Keytruda’s patent expiration in 2028.
Sandoz GME751. Sandoz is getting two studies underway this month: a phase 1 study in patients with stage 2 and 3 melanoma and a comparative phase 3 study against the reference product in patients with metastatic NSCLC. The estimated completion date is late August 2026, which could result in biological licensing application in mid-2027 and an approval decision in mid-2028.
mAbxience MB12. mAbxience plans to complete its phase 3 trial in 174 patients with stage 4 NSCLC in December 2025. That could also put this pembrolizumab biosimilar in play for 2027. mAbxience is majority owned by Fresenius Kabi, with minority ownership by Teva. In an unsurprising development, on April 4, mAbxience announced a strategic licensing agreement with Teva for an investigational biosimilar in development “for the treatment of multiple oncology indications.” Their other oncology biosimilar candidate (MB11) has not been publicly disclosed, so we think the greater probability is that this applies to the company’s pembrolizumab biosimilar.
Other Potential Players. Formycon’s FYB206 has not yet reached clinical testing. Alvotech lists AVT33 as a pembrolizumab biosimilar that is in preclinical testing. Neuclone had announced a pipeline program for a pembrolizumab biosimilar in 2020, but there has been no update from the company. It has not yet launched a phase 1 study. Shanghai Henlius lists HLX17 on its preclinical pipeline, as well as several combination drugs, including PD-1s, targeting solid tumors. XBrane Biopharma had indicated an interest in its Xtrudane pembrolizumab biosimilar candidate but announced in November 2023 that it was terminating development.
BioXpress Therapeutics seemed to have a development program for its pembrolizumab biosimilar, but nothing has been reported on this for several years. Other manufacturers, like Biocon Biologics, have not disclosed their early-stage oncology candidates (though they have 2).
Other established biosimilar developers, like Coherus Biosciences and Bio-Thera Solutions, have their own proprietary PD-1 inhibitors in the pipeline. It would make little sense for them to have sought an entry into the Keytruda biosimilar sweepstakes.
Other Major Factors to Consider
Based on previous biosimilar approval experience, several factors will no doubt affect launch dates for these pembrolizumab biosimilar candidates.
Based on their extremely high sales figures, we must assume that the PD-1 inhibitors will become early targets for the Medicare Price Negotiation program. This could dramatically affect revenue estimates around the 2028 time frame.
Another important consideration is the probability for skinny label approvals. For example, Merck is actively investigating the use of Keytruda in other indications and in other drug combinations, which could delay certain patent expirations considerably. Finally, we’ve seen licensing arrangements that frequently delayed the launch of other biosimilars, and we anticipate this to also occur in the PD-1 inhibitor category. Potentially, this could result in big royalty revenues for Merck as well as 2029 launches, which may be a $20 billion bounty for the company.
