Noting that two of its COVID-19 vaccine candidates it has been developing with partners exhibited weaker immune response than other COVID-19 vaccines, Merck & Co. today discontinued their development. Two other candidates targeting SARs-CoV-2 will not be affected and the company will continue those development efforts.
The pharma giant said it is ending development of V590, on which it has partnered with IAVI, a nonprofit scientific research organization dedicated to addressing urgent, unmet global health challenges. Merck is also scrapping V591, which it acquired last year from Themis when Merck bought the company last year for an undisclosed price, transforming its Austrian collaboration partner into a wholly-owned subsidiary.
Merck said it acted after reviewing data from Phase I trials for both V590 and V591. Both vaccines were generally well tolerated, but generated immune responses “inferior to those seen following natural infection and those reported for other SARS-CoV-2/COVID-19 vaccines,” Merck said in a statement, without disclosing data or identifying those other vaccines.
Merck said it and its collaborators plan to submit the results of the Phase I studies for V590 and V591 for future publication in a peer-reviewed journal.
“We are resolute in our commitment to contribute to the global effort to relieve the burden of this pandemic on patients, health care systems and communities,” Dean Y. Li, M.D., Ph.D., president, Merck Research Laboratories, said in a statement.
V590 is based on Merck’s recombinant vesicular stomatitis virus (rVSV) platform, which uses an attenuated strain of vesicular stomatitis virus, a common animal virus that has been modified to express proteins that stimulate an immune response. Merck uses the rVSV platform in Ervebo, approved by the FDA in 2019 as the first vaccine designed to protect against Ebola Zaire virus.
V591 is a measles vector vaccine candidate engineered to express SARS-CoV-2 proteins on its surface, using a platform based on a measles virus vector Themis initially licensed from the Institut Pasteur—which had headed a COVID-19 vaccine consortium that included Themis and the University of Pittsburgh’s Center for Vaccine Research. The consortium has been awarded an initial $4.9 million by CEPI, the Coalition for Epidemic Preparedness Innovations.
Merck said it will continue to study the potential of the platforms behind V590 and V591, as well as “pursue broader pandemic-response capabilities.”
Addition through Acquisition
Remaining in Merck’s COVID-19 vaccine pipeline are two other candidates that the company added last year through acquisitions—and for which clinical programs and manufacturing scale-up is progressing, the company said.
One is molnupiravir (MK-4482), which joined Merck’s pipeline when the company acquired Ridgeback Biotherapeutics for an undisclosed price in a deal that closed July 1. Ridgeback remains a subsidiary of Merck and continues to partner on development of the vaccine.
Molnupiravir is an oral novel investigational antiviral agent now under study in mid- to late-phase trials in both hospital and out-patient settings that include:
- MK-4482-001, a 1,300-participant Phase II/III study in hospitalized adults with COVID-19 (NCT04575584)
- MK-4482-002, a 1,450-participant Phase II/III study in non-hospitalized adults with COVID-19 (NCT04575597).
- END-COVID, an estimated 80-participant study assessing molnupiravir on SARS-CoV-2 virus shedding in newly hospitalized adults with PCR-confirmed COVID-19 (NCT04405739).
- A Phase II study of an estimated 204 participants designed to compare molnupiravir vs. placebo as measured by infectious virus detection in symptomatic adult outpatients with COVID-19 (NCT04405570)
The primary completion date for the studies is May 2021, with Merck saying today it expected to release initial efficacy data in the first quarter, “which Merck plans to share publicly if clinically meaningful.”
MK-7110 is a potentially first-in-class investigational recombinant fusion protein designed to modulate inflammatory response to SARS-CoV-2, principally by targeting a novel immune pathway checkpoint.
Merck has cited interim results generated in September from a Phase III trial (NCT04317040) that showed a greater than 50% reduction in the risk of death or respiratory failure in patients hospitalized with moderate to severe COVID-19. Full results from the placebo-controlled study are expected in the first quarter, the company added.
Also last year, Merck added MK-7110 (formerly CD24Fc) to its COVID-19 arsenal when it purchased OncoImmune for $425 million in upfront cash, plus an undisclosed amount of additional payments tied to achieving regulatory and sales-based milestones. That acquisition was completed December 23, 2020.
Commitment from Washington
Last month, Merck received a commitment of $356 million from Operation Warp Speed—the Trump administration-launched effort to support development of COVID-19 vaccines and drugs—toward manufacturing and supply of approximately 60,000 to 100,000 doses of MK-7110 to the U.S. government through June 30, 2021.
Those doses will be packaged and ready to ship in the first half of 2021, should the FDA determine that MK-7110 meets statutory criteria for an emergency use authorization, the government said at the time.
Through Warp Speed, the Biomedical Advanced Research and Development Authority (BARDA) partnered with the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense and Army Contracting Command to make the $356 million available.
Earlier in 2020, Merck also received $38,033,570 in initial funding support from Operation Warp Speed for V590 through an agreement with BARDA.
Merck also said it plans to continue research collaborations focused on COVID-19. In April 2020, Merck and the Institute for Systems Biology launched a research collaboration designed to investigate and define the molecular mechanisms of SARS-CoV-2 infection and the resulting COVID-19, as well as identify targets for drugs and vaccines. Merck later announced research collaborations with Peptidream (in June 2020) and the Hackensack Meridian hospital system (in July 2020).
As a result of halting development of V590 and V591, Merck said it will take a charge against fourth-quarter earnings. The charge will be included in Merck’s generally accepted accounting principles (GAAP) results, but will not impact non-GAAP results.
Merck is set to release fourth-quarter and full year 20920 earnings results on February 4.
“We are grateful to our collaborators who worked with us on these vaccine candidates and to the volunteers in the trials,” Li added.