Tag: molnupiravir

Categories : COVIDTags :

Paxlovid Ramped up and No ‘Red Flags’ for Omicron Yet

On By ModernMedia
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In the face of a renewed global surge in COVID cases, Pfizer has ramped up production of Paxlovid, even while the efficacy of Merck’s molnupiravir appears to be less than believed.

Pfizer is now expecting to make 80 million courses of Paxlovid by the end of 2022, Pfizer CEO Albert Bourla told CNBC, a significant increase over its earlier planned capacity of 50 million courses.

This news came after Merck reported the risk reduction in hospitalisation and death from its COVID antiviral, molnupiravir, fell from 50% in the interim analysis to 30% in the final analysis. The reduction came after results were updated with participants that became evaluable after the interim analysis. This drop has led to predictions of increased demand for Paxlovid, which has shown an 89% risk reduction in outpatients.

The increase in production comes just in time to fight the Omicron variant, for which South Africa is now better prepared, according to experts.

‘No red flags’
According to Professor Salim Abdool Karim, director of the Centre for the Aids Programme of Research in South Africa, the numbers appear to be on the rise across all continents, but as yet there are “no red flags” he said.

Omicron has been identified by South African scientists as a major driver of the spike in cases in Gauteng.

“We have been amazed at how fast the numbers are going up,” he said. “But we were not caught with our pants down. We expected and prepared for a fourth wave. [The scientists] gave us the best fighting chance by giving us information early. We didn’t know exactly when it would come and what it would look like,” Prof Karim said, speaking to the Daily Maverick.

While a number of mutations enable the variant to escape immunity, a clear picture of Omicron’s nature won’t emerge for two to four weeks, he cautioned.

Speaking about travel bans imposed on South Africa by Mauritius, Rwanda, Egypt and the Seychelles, President Cyril Ramaphosa said ahead of a West African tour: “I am concerned. Out of due respect to them, they have their own reasons. We would like to have a discussion with them in a way we prefer that they do not react like our former colonisers who are very quick to close Africa down,” Ramaphosa told journalists.

EU accelerates child vaccinations
EU President von der Leyen has said that vaccines for children aged five to 11 will be available in the bloc by December 13, a week ahead of schedule and that she is pushing for the consideration of mandatory vaccination. This comes amidst news that Omicron was detected in the Netherlands before its first detection in South Africa. Meanwhile, in Asia, South Korea has reported its first five cases of Omicron.

Categories : COVIDTags :

Enzymes Speed up Production of Molnupiravir for COVID

On By ModernMedia
Photo by Louis Reed on Unsplash

Molnupiravir is being developed for the treatment of COVID, which has been submitted for review by the US Food and Drug Administration, but large-scale production to treat COVID is still a challenge. Now, researchers have engineered enzymes to help manufacture the pill, resulting in a much shorter synthesis with a higher yield than current methods. The details of their work are reported in ACS Central Science.

The oral antiviral molnupiravir was originally developed to treat influenza, and works by causing viruses to make errors when copying their own RNA, introducing mutations that inhibit replication. Recently, interim phase 3 clinical trial findings indicated that molnupiravir reduced the risk of hospitalisation and death from COVID for newly diagnosed, at-risk patients, and that it had equal effectiveness against different SARS-CoV-2 variants. Researchers set out to develop a shorter, higher-yielding and sustainable way to synthesise the molecule.

The team came up with a three-step synthesis of molnupiravir from ribose, a sugar molecule. They identified enzymes or chemical treatments to sequentially add the appropriate chemical groups to ribose to generate the molecule. For the second step of the synthesis, the team identified bacterial enzymes that weakly catalysed the desired reactions. Using in vitro evolution, they greatly enhanced these enzymes’ activities. The new synthetic route, which also included a phosphate recycling strategy, was 70% shorter and had a seven-fold higher overall yield than the original route.

Source: American Chemical Society

Categories : COVIDTags :

New Drug Molnupiravir Halves COVID Hospitalisation Risk

On By ModernMedia
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Merck today announced that their investigational oral antiviral drug molnupiravir significantly reduced the risk of hospitalisation or death in a Phase III trial in at risk patients with mild-to-moderate COVID. 

Interim analysis showed that molnupiravir reduced the risk of hospitalisation or death by approximately 50%; 7.3% of patients randomised to receive molnupiravir were either hospitalised or died through Day 29 following randomisation, compared with 14.1% of placebo-treated patients. Through Day 29, no deaths were reported in patients who received molnupiravir, as compared to 8 deaths in patients who received placebo. Study recruitment is being stopped early due to these positive results, and the company plans to submit an application for Emergency Use Authorisation (EUA) to the U.S. FDA as soon as possible.

Molnupiravir is an oral form of a potent ribonucleoside analog that inhibits the replication of SARS-CoV-2. Molnupiravir has been shown to be active in several preclinical models of SARS-CoV-2, including for prophylaxis, treatment, and prevention of transmission. 

All 775 patients had laboratory-confirmed mild-to-moderate COVID, with symptom onset within 5 days of study randomization and were required to have at least one risk factor associated with poor disease outcome at study entry. Across all key subgroups, molnupiravir reduced the risk of hospitalisation and/or death; efficacy was unaffected by timing of symptom onset or underlying risk factor. Additionally, based on the participants with available viral sequencing data (approximately 40% of participants), molnupiravir demonstrated consistent efficacy across viral variants Gamma, Delta, and Mu.

The incidence of any adverse event was comparable in the molnupiravir and placebo groups, as was incidence of drug-related adverse events, and the drug was well tolerated.

In addition, molnupiravir is being evaluated for post-exposure prophylaxis in MOVe-AHEAD, a global, multicenter, randomised, double-blind, placebo-controlled Phase III study, which is evaluating the efficacy and safety of molnupiravir in preventing the spread of COVID within households. 

Source: Merck

Categories : COVIDTags :

Molnupiravir Works by Inducing Mutations in SARS-CoV-2

On By ModernMedia

Researchers have shown that the antiviral drug molnupiravir, currently in clinical trials as a COVID treatment, works by inducing mutations in SARS-CoV-2 which prevent the coronavirus from replicating further.

Since the onset of the corona pandemic, researchers have been developing various vaccines and drugs to varying degrees of success. Previous studies have shown why the antiviral drug remdesivir, the first one approved against COVID, has a rather weak effect on the virus. “Remdesivir does interfere with the [viral] polymerase while doing its work, but only after some delay. And the drug does not fully stop the enzyme,” said Max Planck Director Patrick Cramer. 

Molnupiravir was originally developed to treat influenza and in preliminary clinical trials, the compound is promising against SARS-CoV-2. “Knowing that a new drug is working is important and good. However, it is equally important to understand how molnupiravir works at the molecular level in order to gain insights for further antiviral development,” explained Cramer. “According to our results, Molnupiravir acts in two phases.”

Induced RNA mutations halt replication
Molnupiravir, an orally available drug, becomes activated through metabolisation in the body. When it enters the cell, it is converted into RNA-like building blocks. In the first phase, viral RNA polymerase incorporates the building blocks into the virus’ own RNA. However, unlike remdesivir, which merely slows the viral RNA polymerase, molnupiravir does not interfere with its copying functions. Instead, in the second phase, the RNA-like building blocks connect with the building blocks of the viral genetic material. “When the viral RNA then gets replicated to produce new viruses, it contains numerous errors, so-called mutations. As a result, the pathogen can no longer reproduce,” explained Florian Kabinger, a doctoral student in Cramer’s department.
Molnupiravir also appears to do this for other viruses “The compound could potentially be used to treat a whole spectrum of viral diseases,” said Höbartner, a professor of chemistry at the University of Würzburg. “Molnupiravir has a lot of potential.” 
Currently, molnupiravir is in phase III studies, where it is being tested on a large number of patients and is being evaluated for safety. The US government has already secured 1.7 million doses, at a cost of US$1 billion. However, working out at a cost of nearly US$600 per dose, it will not be cheap.

The researchers published their findings in Nature Structural & Molecular Biology.

Source: Max Planck Institute

Categories : COVIDTags :

Molnupiravir Performs Well Versus COVID in Early Trials

On By ModernMedia

Pharmaceutical giant announced on Saturday that its antiviral drug molnupiravir significantly reduced viral load in COVID patients.

Delivering the information to infectious disease experts, the company said that the drug caused the drop in viral loads five days after administration to COVID patients.

“At a time where there is unmet need for antiviral treatments against SARS-CoV-2, we are encouraged by these preliminary data,” said Wendy Painter, chief medical officer of the US firm, Ridgeback Biotherapeutics, which developed the drug in concert with Merck.

Merck had stopped development of two vaccine candidates earlier on, but has been pressing ahead with two possible treatments for COVID.

The experimental drug, also known as EIDD-2801, is currently in its Phase 2a trials. It would need to complete the third phase trials to gain approval. Molnupiravir was originally developed to treat influenza viruses, and its mechanism of action is thought to be through inducing RNA transcription errors in viruses, leading to a transcription catastrophe. This mechanism also inherently creates a significant barrier for viral escape from the drug.

The clinical trials enrolled 202 participants with COVID, who were not hospitalised. There were no safety alerts for the drug, and the four serious adverse events that did occur were not considered to be associated with the drug, Ms Painter said.

William Fischer, lead investigator of the study and a professor of medicine at the University of North Carolina said that these were promising results, adding: “If supported by additional studies, (they) could have important public health implications, particularly as the SARS-CoV-2 virus continues to spread and evolve globally.”

The company is testing another drug in clinical trials, MK-711, preliminary results for which have indicated a 50% drop in viral load in mild and severe COVID patients.

Source: Medical Xpress