Merck Suggests More IO/ADC Combos To Come Under Oncology Strategy
Executive Summary
The company laid out a three-pronged strategy focused on immuno-oncology, antibody-drug conjugates as well as small molecules, with four programs set to enter pivotal trials this year.
Fresh off a raft of data presentations at the American Society of Clinical Oncology’s 2023 meeting, Merck & Co., Inc. laid out an oncology product development strategy in which immuno-oncology and antibody-drug conjugates (ADC) will play a leading role, along with small-molecule drugs.
Executives from the company assembled for a 5 June investor event in Chicago to lay out how the company plans to remain competitive in an oncology field that has become increasingly crowded with approved IO and ADC drugs as well as pipeline candidates.
Three-Pronged Oncology Development Strategy
Merck Research Laboratories chief medical officer Eliav Barr illustrated how quickly Merck’s oncology pipeline has grown in recent years, particularly in the wake of the US Food and Drug Administration’s initial approval in 2014 of PD-1 inhibitor Keytruda (pembrolizumab), which has a label that has racked up a slew of new cancer indications in the years since.
“It’s an extraordinary move from a world where we were once just Keytruda or Keytruda and a couple of friends to a multipolar pipeline that includes a tremendous number of exciting candidates,” he said. “Keytruda really laid the foundation for improving outcomes in patients with cancer.”
He pointed out 20 drugs in the company’s pipeline, divided into immuno-oncology agents, ADCs and small molecules.
On top of Keytruda itself, immuno-oncology agents include a subcutaneous version of the drug, MK-3475A (pembrolizumab/hyaluronidase), as well as candidates that target CTLA4, LAG3, TIGIT, ILT4 and CD27, along with the Moderna, Inc.-partnered individualized neoantigen therapy, V940/mRNA-4157. ADCs include the anti-ROR1 drug zilovertamab vedotin, the LIV1-directed ladiratuzumab vedotin and two undisclosed ADCs in the clinic.
Senior vice president and head of late oncology development Marjorie Green highlighted four programs in particular, namely V940, the anti-TROP2 ADC MK-2870 and two small molecule drugs, the LSD1 inhibitor bomedemstat and the CYP11A1 inhibitor MK-5684, as beginning registration-directed studies in 2023.
Data presented at ASCO on 5 June from the Phase IIb randomized KEYNOTE-942 trial combining V940 with Keytruda in patients with resected high-risk melanoma showed a 65% reduction in the risk of distant metastasis or death compared with Keytruda alone (HR=0.347, p=0.0063). (Also see "Could Moderna/Merck Cancer Vaccine Succeed Where Others Have Flopped?" - Scrip, 16 Apr, 2023.)
For MK-2870/SKB-264, which Merck is developing under a partnership with China-based Kelun-Biotech that the two announced in December 2022, the company also presented Phase II data in non-small cell lung cancer (NSCLC) at the meeting.
Data for that drug showed a 44% partial response rate, albeit in a small sample of 43 patients and only in Chinese hospitals, with Chinese NSCLC patients tending to more EGFR-driven disease amenable to chemotherapy agents like that ADCs such as MK-2870 deliver to tumors. (Also see "ASCO 2023 – Trop2 Could Validate Merck’s Savvy Deal With Kelun" - Scrip, 4 Jun, 2023.)
The drug could emerge as a competitor to Gilead Sciences, Inc.’s approved anti-TROP2 ADC, Trodelvy (sacituzumab govitecan-hziy), for which the company also presented long-term overall survival (OS) data from the Phase III TROPiCS-02 study in HR-positive/HER2-negative metastatic breast cancer, showing a 3.3-month improvement in OS compared with chemotherapy, with median OS of 14.5 months and 11.2 months in the respective arms.
“We believe [MK-2870] has the potential to benefit patients across multiple tumor types and across multiple lines of therapy,” Green said.
Gilead took control of Trodelvy when it acquired Immunomedics in 2020 for $21bn, with the drug playing a starring role as a “pipeline in a product,” a term that reflects a drug with potential in a range of indications, a strategy that Green alluded to as well with regard to MK-2870. (Also see "Gilead Buys Pipeline-In-A-Product With $21bn Immunomedics Deal" - Scrip, 13 Sep, 2020.)
Barr noted that the company was in a position to explore further combinations of immuno-oncology drugs with ADCs, following the FDA approval in April of the first such combination, Keytruda with Seagen Inc. ’s Padcev (enfortumab vedotin-ejfv) in first-line treatment of locally advanced or metastatic urothelial carcinoma among patients ineligible for cisplatin-containing chemotherapy. (Also see "Merck’s Keytruda And Seagen’s Padcev Become First PD-1/ADC Combo To Win US Approval" - Scrip, 4 Apr, 2023.)
“We strongly believe that this is going to be the first of a whole plethora of IO plus ADC combinations that will help patients,” Barr said.
Merck is clearly aiming to remain a leader in the development of ADCs despite its apparent decision to walk away from an acquisition of Seagen, a company that Pfizer Inc. has since offered to buy for $43bn. (Also see "Seagen, With Two Big Pharma Bidders, Nearly Lost Both" - Scrip, 17 Apr, 2023.) ADCs in development got a lot of attention at the ASCO meeting. (Also see "Antibody-Drug Conjugates Take Their Place On The ASCO 2023 Stage" - Scrip, 30 May, 2023.)
Criticism Of IRA
Merck’s investor event came one day before the company filed a lawsuit against the US government over Medicare drug-pricing negotiation policies stemming from the Inflation Reduction Act (IRA). The news got a lot of attention because Merck is the first company to sue over the IRA, though other companies could follow. One of Merck’s more mature products, the diabetes medication Januvia (sitagliptin), is expected to be part of the first round of drug price negotiations with the Centers for Medicare and Medicaid Services. (Also see "Merck & Co. Files First IRA Suit, Signaling Industry Is Ready To Fight" - Scrip, 6 Jun, 2023.)
Perhaps unsurprisingly, Merck Research Laboratories president Dean Li criticized the IRA, alluding to the five to eight years it can take to do early-stage cancer trials such as KEYNOTE-671 – the study of Keytruda in neoadjuvant/adjuvant NSCLC. That study took eight years following US Food and Drug Administration approval to run. One of the industry’s big arguments against the IRA is that it would dampen enthusiasm for investing in new cancer drugs.
“What is really surprising to me is the lack of energy around the fact that right at the moment that you can grasp victory, it’s in your hands, you’re going to grab defeat,” he said.