With a great demand for antivirals targeting early-onset COVID-19, Merck inked a sub-licensing deal with one of the largest pharmaceutical companies in Bangladesh to produce Molnupiravir (Lagevrio) for distribution to over 100 nations. The deal, part of the Medicine Patent Pool (MPP), has been structured to provide the controversial drug available at lower costs around the world. TrialSite has chronicled what some could consider the controversial journey of this experimental drug—from U.S. taxpayer financing, controversial study results, global distribution in the battle against Pfizer and importantly, generic drugs like ivermectin (and other repurposed approaches) for the lucrative, $10+ billion market for COVD-19 antivirals. 90%+ of COVID-19 cases are mild to asymptomatic and patients would benefit from easy to take oral antivirals to inhibit the progression of the viral infection.
TrialSite provides a brief breakdown of the deal, players, and implications.
What’s the objective of this deal?
Provide molnupiravir as an economical antiviral therapy for COVID-19 in over 100 low-and middle-income countries (LMICs).
What’s the Medicine Patent Pool (MPP)?
Backed by Unitaid, this internationally-focused group based in Geneva, Switzerland was founded in July 2010. Aiming to improve public health by providing lower-cost access to key therapies for HIV, TB, hepatitis C, and other conditions, the aim was to offer greater access to life-saving drugs in LMICs.Subscribe to the Trialsitenews “SARS-CoV-2” ChannelNo spam – we promise
The organization claims in its most recent annual report that in the first 10 years since its inception it has “brought life-saving impact across 148 countries” leading to over 18.55 billion doses of generic medicines to countries in need. The governing board is listed here.
How is MPP financed?
Unitaid is the primary financier with startup costs of $4 million to set up the organization in 2010. For more on the financing check out the latest annual report.
Has the group been successful thus far?
Some research indicates that the MPP offers the world greater generic diffusion in LMICs.
What kinds of partnerships does MPP have with WHO?
Toward the start of the pandemic back in 2020 MPP joined the WHO COVID-19 Technology Access Pool (C-TAP) as reported by WHO.
WHO launched CTAP to facilitate expeditious, equitable, and economical access to COVID-19 medical/health products by growing supply? The program was set up to hopefully become a “one-stop-shop for developers of COVID-19 therapeutics, diagnostics, vaccines, and other products to share their intellectual property, knowledge, and data, with quality-assured manufacturers through public health-driven voluntary, non-exclusive, and transparent licenses.”
Did Merck start ink deals prior to any approvals?
Yes. TrialSite reported that company executives crisscrossed the globe structuring supply deals with over 30 nations before evidence from the pivotal MOVe-OUT study was available. In one later press release, Merck announced they were producing (“at-risk”) 10 million courses by end of 2021 and at least 20 million courses for 2022.
By December 22, the company had already shipped products to 12 counties.
What did the pivotal MOVe-Out study reveal?
As reported by TrialSite in late November, Merck first release preliminary numbers showing superior results, then several weeks later issued another press release with adjusted findings. On Oct. 12, TrialSite reported on Merck’s submission of application for emergency use authorization (EUA) to the U.S. Food and Drug Administration (FDA) based on the promising data the company disclosed back on Oct. 1.
Merck shared that the MOVe-OUT study’s independent Data Monitoring Committee stopped the study as the planned interim data analysis of MOVe-OUT revealed molnupiravir reduced the risk of hospitalization or death by approximately 50%. They published that 7.3% of patients who received the drug were either hospitalized or died through Day 29 post-patient randomization (28/385) as compared to 14.1% of the placebo-treated patients (53/377).
Fast forward to Friday, Nov. 26, and the company’s most recent data revealed the risk of hospitalization or death from 9.7% in the placebo group (68/699) to 6.8% (48/709) in the molnupiravir for an absolute risk reduction of 3.0%—that’s right; the true risk reduction this drug affords for billions of dollars stands at 3%. TrialSite did commend the New Jersey drug producer for acknowledging the ARR figure.
Some safety concerns persisted especially for pregnant women or patients actively working to have children.
Are there any ethical questions with the drug?
In the controversial ivermectin debate, Merck took a proactive stance, declaring its own drug could be dangerous. Of course, it did this knowing billions of doses have been administered to fight parasitic diseases in the tropics—very successfully—as part of the Mectizan program. TrialSite suggests a confluence of interests organized a public relations campaign to taint or even vilify the use of ivermectin as a means of opening the COVID-19 early treatment antiviral market to pharmaceutical products including this one. TrialSite has written extensively on this topic—search the media site for stories on this matter. Merck knows very well that the drug (ivermectin ) has a very safe profile if prescribed by a licensed physician.
Importantly, TrialSite reported during the summer of 2021 that Merck received $356 million in U.S. taxpayer money by the end of 2020 to fund the development of COVID-19 fighting products. Moreover, by then, they secured $1.2 billion in guaranteed purchases by the U.S. government. Clearly, the impetus for the company was branded designer drugs over economic repurposed options.
Other initiatives raised some concerns as well. For example, TrialSite reported that the health agency of Vietnam’s biggest city, Ho Chi Minh City, set up a program distributing the drug as part of public health care—not part of a clinical trial. Much like the public health agency of Uttar Pradesh used ivermectin as part of a health kit, in Ho Chi Minh City the public health department used experimental molnupiravir.
What’s Molnupiravir status?
The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) issued an approval of the antiviral molnupiravir on November 4, 2021—the first major regulatory authority to issue an approval. A controversial move, this decision was based on preliminary, non-reviewed data.
Although there are health and safety concerns with this experimental drug (more below) the United States Food and Drug Administration (FDA) issued an Emergency Use Authorizations (EUA) on December 22, 2021.
On the concerns for safety TrialSite reported in October 2021, some scientists expressed concern that the drug could cause birth defects or even cancer.
What happened in India with this drug?
Of note Balram Bhargava, a high-level doctor in India’s apex medical research organization called Indian Council of Medical Research (ICMR) declared that despite the approval of the drug by this nation’s drug regulatory body—the Drugs Controller General of India (DCGI)—the drug had “major safety concerns.”
The Times of India and several other media in the world’s second-most populous nation report that an ICMR national task force focused on COVID-19 would opt to not recommend the antiviral drug molnupiravir in their clinical management protocol for COVID-19.
What’s the latest deal in Bangladesh?
Now, Merck has cut a deal with Incepta Pharmaceutical Ltd., one of the largest pharmaceutical companies in Bangladesh to produce the drug as part of the MPP.
What’s Incepta Pharmaceuticals’ background?
A “flagship pharmaceutical firm” for Bangladesh, the company formed in Dhaka back in 1999 and is now chaired by Abdul Muktadir. The company maintains a couple of major production facilities in Savar and Chamrai and manages 23 large depots through which the firm distributes drugs across this nation of approximately 165 million people. The company has supplier relationships with nearly 70 nations around the world. The company produces over 1100 products.