A new joint development program testing Eisai Co. Ltd.'s Lenvima (lenvatinib mesylate), an oral tyrosine kinase inhibitor, both alone and together with Merck & Co. Inc.'s anti-PD-1 therapy, Keytruda (pembrolizumab), across a dozen cancers could yield a multibillion-dollar payout for the Tokyo-based company while opening up new markets for both partners. The far-reaching deal completes a triplet of immuno-oncology-focused bets by Merck following earlier tie-ups with Astrazeneca plc last year and Ablynx NV in 2015.
Frank Clyburn, president of Merck's global oncology business line, told BioWorld the collaboration complements the company's overall strategy, "which is focused on the rapid advancement of innovative monotherapy approaches and synergistic combinations to help the broadest range of cancer patients.
"Business development is a priority for Merck and this collaboration is an example of how we're actively engaged in finding the best external science to further augment our pipeline and portfolio in a financially disciplined way," he said.
The companies pointed to Merck's commercial and medical expertise and Eisai's real-world evidence for Lenvima as factors that could expedite patient access to the drug, especially for hard-to-treat refractory cancers.
Shares of Eisai (Tokyo:4523) rose about 9.8 percent on Thursday to close at ¥6,126 (US$57.65), while Kenilworth, N.J.-based Merck shares (NYSE:MRK) held steady, closing at $54.76 on Thursday, up just 29 cents from their previous close.
The new agreement adds 11 potential indications across six cancer types to work already underway. Altogether, the efforts could yield up-front, option and regulatory and sales milestone payments of up to $5.76 billion assuming across-the-board success. Those payments include $300 million for Eisai up front and up to $650 million for certain option rights, as well as $450 million in reimbursement for R&D expenses. The partners will share profits equally, including from sales of Lenvima for currently approved indications. They will split expenses on the program, too.
New joint studies pursued by Merck with Eisai will evaluate combinations of Lenvima and Keytruda in endometrial cancer, non-small-cell lung cancer, hepatocellular carcinoma, head and neck cancer, bladder cancer and melanoma, as well as in a basket trial targeting multiple cancer types.
The companies are also pursuing a combination approach in renal cell carcinoma (RCC), an indication for which the drug combo has FDA breakthrough status following the phase Ib/II Keynote-146 study. That indication is the subject of an ongoing Eisai-sponsored phase III trial, called Study 307, which is comparing the currently approved combination, Lenvima plus everolimus, to Lenvima plus Keytruda. Also underway is a similar phase Ib study, Keynote-523, in Japanese patients with unresectable solid tumors and a phase Ib study of the combination in hepatocellular carcinoma in Japan and the U.S.
The synergy created by combining Lenvima and anti-PD-1 inhibitors has been suggested to be due to the reinforcement of the antitumor activity of anti-PD-1 inhibitors through Lenvima's stimulation of the immune system, a spokesperson for Merck told BioWorld. Furthermore, clinical and nonclinical studies have suggested that combining the drugs offers efficacy that not only exceeds either agent alone, but that is evidenced regardless of patient background such as prior treatment, PD-L1 expression, or the state of microsatellite instability, the spokesperson said.
The agreement between Eisai and Merck has echoes of the alliance formed last July between Merck and Astrazeneca covering the co-development and co-commercialization of Astrazeneca's oral PARP inhibitor, Lynparza (olaparib), for multiple cancer types. Launched with 14 indications in its sights, that deal carries up to $8.5 billion in total consideration, including $1.6 billion up front for Astrazeneca. Before that, Merck struck a separate immuno-oncology collaboration deal with Ghent, Belgium-based Ablynx, covering up to 17 Ablynx Nanobody programs against individual protein targets and target combinations. In June 2017, Ablynx said it had achieved a second milestone in the agreement, triggering a €2.5 million (US$3.1 million) payment from Merck. (See BioWorld, July 28, 2017, and July 31, 2017.)
Eisai has already made substantial progress with Lenvima on its own, securing approval to market it as a monotherapy for differentiated thyroid cancer in more than 50 countries, including the U.S., Japan and Europe. It has also obtained approval to market the therapy in combination with everolimus for the treatment of RCC patients who have failed previous anti-angiogenic therapy.
Eisai sales of Lenvima hit $194 million in 2017. Meanwhile, Merck's Keytruda raked in revenues of $3.81 billion the same year, more than doubling the $1.4 billion in sales that it generated in 2016, and making it Merck's second best-selling product after the diabetes therapy Januvia/Janumet (sitagliptin).