Merck to hunt emergency authorization for oral Covid-19 therapy

A nurse tends to a Covid-19 patient at SSM Health St. Anthony Hospital in Oklahoma City on August 24, 2021.

Nick Oxford | Reuters

Merck and Ridgeback Biotherapeutics plan to apply for emergency approval for their oral antiviral treatment for Covid after the drug shows “compelling results” in clinical trials.

The drug molnupiravir reduced the risk of hospitalization or death in patients with mild or moderate cases of Covid by around 50%, the companies said on Friday. Molnupiravir is given orally and works by stopping the coronavirus from replicating in the body.

An interim analysis of a Phase 3 study found that 7.3% of molnupiravir-treated patients were hospitalized within 29 days. Of the patients who received a placebo, 14.1% were hospitalized or died on day 29. No deaths were reported in patients receiving molnupiravir within the 29-day period, while eight deaths were reported in placebo-treated patients.

All 775 study participants had laboratory-confirmed symptomatic Covid-19 and were randomly assigned molnupiravir or a placebo within five days of symptoms.

Each participant was unvaccinated and had at least one underlying factor that placed them at a higher risk of developing a more severe case of the virus. The most common risk factors included obesity, over 60 years of age, and diabetes or heart disease.

The phase 3 part of the study was conducted in more than 170 locations in countries such as the United States, Brazil, Italy, Japan, South Africa, Taiwan, and Guatemala.

The study showed that molnupiravir’s effectiveness was not influenced by the time when symptoms appeared or the patients’ underlying risk factors. It was also shown to be consistently effective in treating all variants of Covid, including the widely used and highly transferable delta expansion.

Side effects were similar in the molnupiravir and placebo groups, with approximately 10% reporting adverse events. Only 1.3% of the molnupiravir group discontinued therapy because of an adverse event – less than the 3.4% of the placebo group who did.

Recruitment for the study will be terminated prematurely based on the positive results on the recommendation of an independent data monitoring committee and in consultation with the US Food and Drug Administration.

Merck is also testing molnupiravir in a separate global phase 3 study to evaluate its effectiveness in preventing the spread of Covid in households.

“Profound Effect”

Robert M. Davis, CEO and President of Merck, said in a press release on Friday that the company would do everything possible to get molnupiravir to patients as soon as possible.

“With these compelling results, we are optimistic that molnupiravir can become a key drug in the global effort to fight the pandemic,” he said.

Wendy Holman, CEO of Ridgeback Biotherapeutics, added, “As the virus continues to be widespread and the therapeutic options currently available are infused or require access to a health facility, antiviral treatments can be taken at home to help people with Covid-19 from the To keep disease away hospital urgently needed. “

“We are very encouraged by the results of the interim analysis and hope that molnupiravir, if approved for use, can have a profound impact on the control of the pandemic,” she said.

Authorization to use in an emergency

Merck said Friday it plans to apply for emergency approval for the drug in the US as soon as possible. The company also plans to file regulatory filings with other international drug regulatory agencies.

If approved by regulators, molnupiravir could be the first oral antiviral drug for Covid. Currently used antiviral treatments, such as Remdesivir, are administered intravenously.

Merck has already started production of molnupiravir. The pharmaceutical giant expects to produce 10 million treatment cycles by the end of 2021 and more doses in 2022.

The company agreed earlier this year to ship approximately 1.7 million molnupiravir courses if it receives FDA emergency or full approval.

Merck has also entered into supply and purchase agreements with other governments for the drug – pending regulatory approval – and is in talks with other governments regarding the supply of molnupiravir.

The company plans to implement a tiered pricing approach based on World Bank income criteria to ensure molnupiravir is available worldwide. Merck previously announced that it had entered into non-exclusive, voluntary licensing agreements for molnupiravir with generic drug companies to facilitate access to treatment for low- and middle-income countries. Approvals or emergency approvals from the local supervisory authorities are also pending for these agreements.

Profit sharing

Ridgeback received an upfront payment from Merck as part of the company’s development of molnupiravir. The company is also eligible for contingent payments based on development and regulatory approval milestones.

Profits from the collaboration will be shared equally between Merck and Ridgeback.

Vaxart shares plunge on weak antibody response to oral vaccine

An experiment Coronavirus The orally taken vaccine showed promising results in an early clinical trial of 35 healthy adults from South San Francisco Vaxart said Wednesday. Despite the results, Vaxart’s stock fell about 57%.

Vaxart scientists divided volunteers between the ages of 18 and 54 into three groups. The first group received two low doses of the vaccine – called VXA-CoV2-1 – 29 days apart, while the remaining groups received a single low or high dose.

The vaccine, contained in a small tablet, produced a type of T cell responsible for killing virus-infected cells in about 75% of the volunteers who received a single low or high dose. It is said that the reported responses are higher than those in Modern and Pfizers Vaccinations.

However, neutralizing antibodies were not detected in volunteers after a single dose, Vaxart said. Researchers believe that the antibodies play an important role in the defense of cells against the virus. The company said it is currently testing second-dose antibody responses after antibodies were detected in two-dose volunteers’ nasal swab samples.

Isaac Bogoch, an infectious disease specialist and professor at the University of Toronto, said the company’s shares could fall after the first dose due to the lack of neutralizing antibodies.

“The immune response is diverse,” he said, adding that one aspect of the immune response is to make antibodies, especially neutralizing antibodies. “While it is great to see that there seems to be a decent T-cell response, the lack of antibodies detected is problematic and can reduce the effectiveness of this vaccine.”

The company said no serious adverse events were reported in the Phase 1 study, with side effects generally being mild. Volunteers reported common side effects such as headache and fatigue, and there was a “slight increase” in the high-dose group of loose stool cases, the company said.

The data will be presented on Wednesday afternoon at the New York Academy of Sciences symposium.

“The most exciting thing about the [phase one data] is that we can get a very, very strong T-cell response even after one dose, “Sean Tucker, Vaxart’s chief scientific officer, told CNBC in a telephone interview, adding that T-cells do compared to antibodies fighting the virus is likely to be “underestimated”.

The biotech company said the vaccine has the potential to provide better protection against current and emerging strains of the virus than existing vaccines. Moderna, Johnson & Johnson, and Novavax have said in the past few days that their vaccines may be less effective against B.1.351. highly contagious strain found in South Africa. US officials have raised concerns that Covid may continue to mutate and defy the protection of existing vaccines.

Vaxart’s vaccine contains DNA instructions for making the spike protein that allows the virus to enter human cells, as well as instructions for making the N protein, which is involved in other processes. Tucker said the inclusion of the N protein could cause the vaccine to retain its ability to work against emergent strains.

Many other vaccines under development chose spike protein as a “primary target,” he said. “But the problem with that [spike] Protein it definitely mutates more over time. We also added the N protein, which is highly conserved in the virus. “

According to Vaxart, the vaccine is the only oral tablet in the US that has been tested in humans. Similar technology is being used to develop vaccines against influenza and norovirus.

The company was investigated and investigated by the federal government late last year for allegedly exaggerating its involvement in Operation Warp Speed, former President Donald Trump’s vaccines and treatments program. It said in a press release in June that “Vaxart’s Covid-19 vaccine was selected for US government’s Operation Warp Speed,” which rocketed its stocks.

However, it found that the company had received no federal government funding for vaccine doses and was only participating in preliminary U.S. studies to identify potential areas for potential Warp Speed ​​partnership and support. according to the New York Times.

Tucker told CNBC the company is in talks with the US and other governments to find possible ways to collaborate on its vaccine.

If Vaxart’s vaccine goes through other clinical trials and US approval, it could offer advantages over needle-based vaccines.

Dr. Paul Offit, a member of the FDA’s Advisory Committee on Vaccines and Allied Biological Products, said that an orally taken vaccine may be better accepted by the public who may be afraid of needles. Two US-approved Covid-19 vaccines – from Pfizer and Moderna – are injected into the arm and require two injections three to four weeks apart.

Vaxart said his vaccine is stable even at room temperature and does not require a freezer, which means it “can be stored and delivered to mass populations around the world”. For comparison: Pfizer’s vaccine is a must stored in ultra-cold freezers that keeps it between negative 112 and negative 76 degrees Fahrenheit. Moderna vaccine must be delivered between 13 and 5 degrees Fahrenheit.

Vaxart said the vaccine also doesn’t require any special medical training and can be taken at home. This will help comply with social distancing guidelines while relieving the burden on the health system.

The company said it was still critical whether it was single- or two-dose therapy.

A phase 2 study is expected “in the next few months,” Tucker said. In its “Fastest Accelerated Timeline,” the company expects Phase two and three studies to be completed by early 2022.

– CNBCs Hugh Son contributed to this report.