Virus World

Merck announced it is stopping development of both of the current formulations of the Covid-19 vaccines the company was working on. Merck said Monday it will stop developing both of the current formulations of the Covid-19 vaccines the company was working on, citing inadequate immune responses to the shots. Work will continue on at least one of the vaccines, which is being developed in partnership with the International AIDS Vaccine Initiative (IAVI), to see if using a different route of administration would improve how effective it is. The announcement marks a shocking setback for one of the most storied vaccine makers, and will raise tensions around readouts expected soon from other companies, including Johnson & Johnson and the upstart NovaVax. Merck said it remains committed to research on Covid-19 and will focus on two treatments it is developing. One is an antiviral medicine against SARS-CoV-2, the virus that causes the disease. The other is a medicine aimed at helping hospitalized patients by reducing the immune system’s over-response to the virus; it has already shown promise in clinical studies. “We’re disappointed by this result,” Nick Kartsonis, a senior vice president for infectious disease and vaccines at Merck Research Laboratories, said in an interview with STAT. “But it also allows us to continue to focus on our therapeutic candidates and move those forward. And, you know, we are open to continue the work to see if we can address the pandemic in any way we can add value.”

The results from a Phase 1 trial, described briefly in Merck’s press release, were resoundingly disappointing. The hope was that Merck’s vaccines, which were unique because they used viruses that could replicate once they were in the body, would be long-lasting, one-dose vaccines. The virus used for the vaccine being developed with IAVI is the one used in Merck’s successful vaccine against Ebola. The other vaccine used measles virus, a type of vaccine Merck has manufactured for decades. Both vaccines, however, produced lower levels of antibodies against SARS-CoV, including binding antibodies and neutralizing antibodies, than is seen in the blood of individuals who have recovered from Covid-19. Kartsonis said it was difficult to compare results from different studies because researchers have used different assays to measure antibody levels. But it appears neither vaccine performed as well as the Pfizer/BioNTech and Moderna vaccines, which resulted in antibody levels several times above those seen in people who have recovered from Covid-19, and the AstraZeneca/Oxford vaccine, which led to antibody levels roughly equivalent to those seen in people who have recovered from Covid-19. There are biologically plausible explanations for why the vaccine Merck was developing in partnership with IAVI underperformed in the Phase 1 trial, IAVI President Mark Feinberg told STAT. The vaccine was administered by intramuscular injection; an oral or intranasal administration route might work better, he said. “While these data are disappointing, this is not the end of the program for us,” Feinberg said.

Merck Press Release (Jan. 25, 2021):

https://www.merck.com/news/merck-discontinues-development-of-sars-cov-2-covid-19-vaccine-candidates-continues-development-of-two-investigational-therapeutic-candidates/ 

AstraZeneca should still know by year-end whether its experimental vaccine protects people against coronavirus, as long as it is cleared to resume trials soon, its chief executive said on Thursday amid doubts over its rollout. Governments desperate to put an end to the COVID-19 pandemic which has caused more than 900,000 deaths and huge economic and social disruption during 2020 are pinning their hopes on a vaccine. However British drugmaker AstraZeneca suspended late-stage trials on its potential vaccine this week after an illness in a participant in Britain who was reported to be suffering from symptoms associated with transverse myelitis, a rare spinal inflammatory disorder. The World Health Organization (WHO) has flagged the AstraZeneca vaccine, which is being developed with the University of Oxford, as the most promising for coronavirus.

CEO Pascal Soriot said during an online event on Thursday that AstraZeneca (AZN.L) did not yet know the diagnosis of the participant who was ill, adding that it was not clear if the volunteer had transverse myelitis and more tests were needed. The diagnosis would be submitted to an independent safety committee and this would usually then say whether trials can be resumed, Soriot said, adding it was usual for such pauses. “It’s very common, actually, and many experts will tell you this,” Soriot said, adding: “The difference with other vaccine trials is, the whole world is not watching them, of course. They stop, they study, and they restart.” Shares in AstraZeneca fell on Wednesday after the trial halt raised doubts about the timeline for the vaccine’s rollout.

AstraZeneca would supply vaccines to countries at the same time to ensure a fair and equitable distribution, Soriot said, reiterating that the company was close to having capacity to produce 3 billion doses at sites set up around the world to prevent governments from restricting distribution. With up to 60,000 people set to participate in the study program, AstraZeneca’s CEO said the volume was typical of vaccine trials and large enough to spot rare side effects. “With this you are going to pick up very rare events.” he said, adding that a planned staggered launch, prioritizing at-risk groups, would provide further assurance for the masses that are set to be covered by government plans at a later stage. Serum Institute of India, one of AstraZeneca’s (AZN.L) development and production partners, said on Thursday it was joining the suspension, backtracking on remarks that it did not face any issues.

Transverse myelitis cases after a vaccination have been documented before, but concrete links between the condition and vaccinations have not been established, experts said. The U.S.-based Mayo Clinic concludes that the association so far is not strong enough to warrant limiting any vaccine. A 2009 review in the journal Lupus of nearly 40 years of English-language publications found 37 cases of transverse myelitis associated with hepatitis B vaccines, measles-mumps-rubella, diphtheria-tetanus-pertussis and others.  The vaccines remained on the market, Stephen Evans, a professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, said. Linking such an autoimmune response to a single factor like a vaccine is problematic, he said, given the number of immunological, hormonal or environmental factors at play. “It’s terribly difficult to be sure,” Evans said. 

RBC Capital Markets analyst Bryan Abrahams cautioned the trial participant’s condition must be thoroughly investigated. “Even a single case could possibly imply a rate or association higher in the study than what is normally observed sporadically” he wrote to investors, adding a one in 10,000 risk, if confirmed, would likely be unacceptable. BioNTech (BNTX.O), among the frontrunners in the vaccine race with partner Pfizer (PFE.N), echoed remarks by Soriot that clinical halts are a common feature of immunization trials. 

“Safety is a top priority,” its CEO Ugur Sahin told Reuters.