Although the headline advises against getting too excited, this may be the most exciting news we have heard so far.
On October 1, 2021 (U.S. time), the world’s second-largest vaccine manufacturer, Merck & Co., Inc. (known as MSD, and as “Merck” in the United States and Canada), announced that interim Phase 3 data for Molnupiravir, an investigational oral anti-SARS-CoV-2 drug co-developed by the company and Ridgeback Biotherapeutics for the treatment of patients with mild-to-moderate COVID-19, demonstrated a reduction in the risk of hospitalization and death by approximately 50% compared to the placebo group.
The announcement sent shockwaves through the market. Following the release of the news, Merck (MRK.N) saw its intraday gain exceed 12% on Friday, before closing up 8.44% at $81.45 per share. This marked the stock's largest intraday surge since 2009, bringing its market capitalization to $206.2 billion. Furthermore, the news appeared to buoy the broader U.S. equity market, as all three major indices rebounded on Friday: the Dow Jones and S&P 500 both rose by more than 1%, while the Nasdaq ended a five-day losing streak.
While some rejoiced, others worried, as this major news from MSD triggered a widespread decline in vaccine stocks—Novavax fell 12.21%, Moderna fell 11.37%, BioNTech fell 6.67%, Gilead Sciences fell 1.85%, AstraZeneca fell 0.63%, and Pfizer fell 0.26%.
MSD and Ridgeback stated that they will submit an application for Emergency Use Authorization (EUA) to the U.S. Food and Drug Administration (FDA) as soon as possible, and will also submit applications globally. If approved, molnupiravir will become the world's first oral antiviral drug for COVID-19.
Anthony Fauci, America’s top infectious disease expert and director of the National Institute of Allergy and Infectious Diseases, explained to *The New York Times*: “I woke up in the morning not feeling well, with a loss of smell and taste, and a sore throat. I called my family doctor and said, ‘I have COVID, please give me a prescription.’” This means that in the future, individuals with confirmed infections will be able to take medication at home without having to queue at hospitals, which is also a boon for those who fear injections.
In the Phase III trial, MSD and Ridgeback applied strict eligibility criteria for enrolled patients, who were required to have mild to moderate disease (within 5 days of symptom onset), be unvaccinated, and possess at least one high-risk factor associated with poor disease prognosis, such as advanced age, obesity, diabetes, or underlying comorbidities like heart disease. Pregnant women were excluded.
Based on the trial results, on day 29 post-randomization, the rate of hospitalization or death in the molnupiravir treatment group was 7.3% (28/385), with no deaths reported. In contrast, 53 patients in the placebo group were hospitalized or died (53/377), accounting for 14.1%, with 8 deaths. The data indicate that molnupiravir reduced the rate of hospitalization or death by 50% (p = 0.0012). This demonstrates that molnupiravir can effectively reduce the mortality rate among patients with these high-risk factors.
Image source: WeChat Official Account “Armstrong Biologics News”
In the trial, physicians will prescribe molnupiravir to patients in the treatment group. After receiving the tablets in the ward, patients will take 4 tablets twice daily for a 5-day course of treatment.
Dean Li, Head of Global Research and Development at MSD, said in an interview: "The name Molnupiravir is indeed fitting—it is named after Mjölnir, the hammer of Thor. This drug is a hammer against the novel coronavirus, no matter what variants it evolves into."
He stated that, based on the trial data, this drug is equally effective against SARS-CoV-2 variants, including the Gamma, Delta, and Mu variants. This will curb the spread of the novel coronavirus.
MSD stated that it aims to produce 10 million treatment courses of the drug by the end of this year and plans to scale up production next year. However, the drug remains costly. Under the agreement between MSD and the U.S. government, once the medication receives Emergency Use Authorization (EUA), the U.S. government will purchase 1.7 million treatment courses for $1.2 billion, equating to approximately $700 per course. Nevertheless, this price represents only one-third of the cost of Regeneron’s monoclonal antibody therapy. Although its efficacy may not match that of monoclonal antibodies—which are primarily administered via intravenous infusion and require patients to visit hospitals or clinics—the drug offers a more accessible treatment option.
MSD stated that its goal is to benefit the global community, and it has entered into licensing agreements with five Indian generic drug manufacturers to accelerate the supply of the drug to over 100 low- and middle-income countries. It will adopt a "tiered pricing approach," setting drug prices to reflect each country's ability to pay.
However, MSD has not yet disclosed the adverse effects of molnupiravir, nor has it undergone peer review. Dean Li has, however, promised to release additional data at a later date.
However, in a WeChat group, an analysis shared from "Tongxieyi", an exchange and value-sharing platform focused on innovative drug development, appears quite plausible. The analysis suggests that for molnupiravir, the strategy from patient selection criteria to clinical endpoints, and further to regulatory submission based on interim analysis results, seems designed to validate data reliability in order to expedite the drug approval process.
Screenshot from: Tongxieyi
According toReport from the WeChat Official Account "New York Time", Molnupiravir is not a newly developed drug; it originated in a laboratory at Emory University in 2013, where researchers initially aimed to treat equine encephalitis virus infections. However, subsequent testing revealed that, as a broad-spectrum antiviral agent, it can inhibit the replication of various RNA viruses, including influenza viruses, SARS and MERS (Middle East Respiratory Syndrome) viruses, Ebola virus, and respiratory syncytial virus. In March 2020, Miami-based Ridgeback Biotherapeutics secured the licensing rights for the drug. Two months later, Merck stepped in to co-invest in its development. Prior to this, MSD's own two COVID-19 vaccine development programs had ended in failure.
As the tables turn, MSD has regained its presence in the fight against the COVID-19 pandemic. Citing forecasts from multiple Wall Street analysts, The New York Times reported that the drug is expected to generate $10 billion in annual revenue for MSD and Ridgeback Biotherapeutics.
However, considering the U.S. government’s “America First” policy on vaccine distribution and its various poor performances over the past year, we clearly cannot expect it to be willing to share Molnupiravir with us.
To forge iron, one must be strong oneself; the R&D of domestic COVID-19 therapeutic drugs must also be accelerated.