Merck Shutters COVID-19 Vaccine Programs, Shifts Focus to Therapeutics

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Merck announced that it is going to stop developing its two COVID-19 vaccine candidates, dubbed V590 and V591, after poor responses in Phase I trials. They are shifting their attention to advancing two therapeutic drugs for COVID-19, MK-4482 and MK-7110.

Merck came late to the vaccine race when it acquired Austria-based Themis in May 2020. The same month, it partnered with Florida-based Ridgeback Therapeutics to develop MK-4882, which is an orally-available antiviral candidate. And in November, it acquired Maryland-based OncoImmune and its COVID-19 candidate CD24Fc (MK-7110) for $425 million in upfront cash.

In the Phase I trials, V590 and V591 were generally well tolerated, but the company reports that immune responses were inferior to what was observed in people who recovered naturally from COVID-19 infections.

“We are grateful to our collaborators who worked with us on these vaccine candidates and to the volunteers in the trials,” said Dean Y. Li, president, Merck Research Laboratories. “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.”

Merck has a history of successful vaccine development, so it was a bit surprising when they came so late to the COVID-19 vaccine arena. They chose a traditional approach of utilizing weakened viruses. The V590 leveraged technology from the company’s Ebola vaccine, and the V591 tech is based on a measles vaccine utilized in Europe. The company only finished recruiting volunteers for the Phase I study close to the end of 2020, while Pfizer-BioNTech and Moderna were at that time already reporting Phase III data and submitting packages to the U.S. Food and Drug Administration (FDA) for Emergency Use Authorization (EUA). Both companies’ COVID-19 vaccines are being dosed throughout the U.S. and Europe.

Nick Kartsonis, senior vice president of clinical research for infectious diseases and vaccines at Merck Research Laboratories, said the results of the Phase I trials were “disappointing, and a bit of a surprise.” Both vaccines created fewer neutralizing antibodies than other COVID-19 vaccines.

“We didn’t have what we needed to be able to move forward,” Kartsonis told Bloomberg in a Sunday interview.

The federal government’s Operation Warp Speed provided financial support to the develop of six vaccine programs, one of which was Moderna. Pfizer-BioNTech did not receive development support, although it did sign a contract to supply the vaccine. Merck was not one of Operation Warp Speed’s portfolio companies. Instead, it partnered with the International AIDS Vaccine Initiative (IAVI) and received some government research funding. Both of the vaccines were designed to be single shots, instead of the double shots of the Moderna and Pfizer-BioNTech vaccines. The Pfizer-BioNTech shots are given about 21 days apart and the Moderna about 28 days apart.

The other two therapeutics are MK-7110, formerly CD124Fc, which is picked up in the OncoImmune acquisition. It is a potentially first-in-class recombinant fusion protein that modulates the inflammatory response to the SARS-CoV-2 virus. It works mostly by targeting a novel immune pathway checkpoint. Interim data from a Phase III trial demonstrated a 50% decrease in the risk of death or respiratory failure in patients hospitalized with moderate to severe COVID-19. They expect a full data readout in the first quarter. In December 2020, Merck inked a supply deal with the U.S. government to advanced manufacturing and distribution of the drug.

The second drug, molnupiravir (MK-4482) is an oral antiviral drug being developed in collaboration with Ridgeback Bio. It is in an ongoing Phase II/III clinical trial in hospitalized patients as well as in out-patient settings. The studies are expected to wrap in May 2021, but Merck has plans for an initial efficacy data release in the first quarter.

Despite the enormous success seen with the Pfizer-BioNTech and Moderna vaccine programs, and other COVID-19 vaccines showing promise, such as Johnson & Johnson’s, the AstraZeneca-University of Oxford’s, which has been authorized in the UK, and Novavax’s, it is not universal. In December 2020, Sanofi and GlaxoSmithKline delayed the launch of their Phase III trial because of insufficient immune responses in older patients in their clinical trial. As a result, they pushed back any likelihood of it being available until the end of 2021, if at all.

The J&J Phase III trial of its vaccine may be ready for a data readout this week or next, potentially. On January 14, 2021, the company published interim Phase I/II data on the vaccine, noting it had created an immune response that lasted at least 71 days. The 71-day mark was associated with the interim data point in participants aged 18 to 55 years.

The data demonstrated that the vaccine induced an immune response and was generally well-tolerated. Neutralizing antibodies against SARS-CoV-2, the virus that causes COVID-19, were observed after a single vaccination in more than 90% of volunteers at Day 29 and 100% of the volunteers between the ages of 18 and 55 at Day 57.

A fourth vaccine, developed by AstraZeneca and Oxford University, has been authorized in the U.K., but is probably several months away from even submissions in the U.S. It was authorized on December 30, 2020, by the UK Medicines and Healthcare products Regulatory Agency (MHRA). Like the Pfizer-BioNTech and Moderna shots, it requires two doses three or four weeks apart.

The UK authorization was based on data from clinical trials performed in the UK and Brazil. The US-based trial is still ongoing. Interestingly, it was reported that in the U.S., some people in the trial became eligible to receive the Pfizer-BioNTech or Moderna vaccines.

Another vaccine in development, is Novavax’s. Australia’s Therapeutic Goods Administration (TGA) granted a provisional determination to the company’s vaccine this week, meaning the company can then apply for provisional registration, which is the step prior to submitting clinical data for provisional approval. Novavax is also running a separate UK trial, which completed enrollment of more than 15,000 volunteers. A data readout is expected this quarter. In the U.S., the Novavax trial began on December 28, 2020.