US government rights in patents on Molnupiravir, based upon funding of R&D at Emory University

Resource: KeiOnline

Molnupiravir, the oral pill that is showing promising results as a potential treatment for covid-19, was invented at Emory University with U.S. government funds. After more than six years of non-clinical testing, Emory licensed molnupiravir to Ridgeback Biotherapeutics to continue its development as a potential treatment for covid-19. The discovery and further research efforts made at Emory between 2013 and 2020 benefited from an estimate of $35 million dollars in government support. As a consequence of these investments, the U.S. government has rights in key molnupiravir patents.

This blog overviews the role of the U.S. government in the research and development leading to molnupiravir, as well as co-owner of key patents directed to this drug.

Emory conducted extensive non-clinical testing

Emory scientist George Painter started working on molnupiravir-like compounds in 2013 after he was approached by the Defense Threat Reduction Agency (DTRA). The DTRA was looking for a way to fight Venezuelan equine encephalitis, a deadly disease that causes brain swelling. Painter and colleagues at the Emory Institute for Drug Development (EIDD) screened for libraries of known antiviral drug compounds and identified a potential candidate named EIDD-1931. To improve in vivo pharmacokinetics, they created a prodrug based on the chemical structure of EIDD-1931. That prodrug,  originally called EIDD-2801, is now better known as molnupiravir.

From 2013 to 2020, EIDD researchers conducted extensive non-clinical testing to investigate EIDD-1931 and molnupiravir as potential treatments for infectious diseases. Among other findings, their experiments demonstrated that EIDD-1931 is effective in protecting mice from lethal Venezuelan equine encephalitis and inhibit Middle East respiratory syndrome CoV (MERS-CoV) with minimal cytotoxicity. EIDD scientists also showed that molnupiravir has broad anti-influenza virus activity in cultured cells and mice. Based on these findings, Emory decided to focus on molnupiravir as a clinical candidate. However, although they were primarily interested in influenza, Painter and other colleagues at Emory also believed that molnupiravir could treat coronaviruses.

When the covid-19 pandemic hit, the Drug Innovation Ventures at Emory (DRIVE) was getting ready to file an Investigational New Drug (IND) application to test molnupiravir in humans. At the time, their disease target was still influenza. However, as the urgent need for covid-19 therapeutics became evident their focus quickly shifted to SARS-CoV-2. But DRIVE concluded that they lacked the resources to scale up for covid-19 clinical trials, and in March 2020 Emory licensed molnupiravir to Ridgeback to continue its development. With Emory paving the way with extensive non-clinical data, Ridgeback was able to quickly receive FDA approval for testing in humans. The non-clinical testing led by Emory was a significant contribution, particularly because some have been skeptical about the safety profile of drugs in the same class as molnupiravir. Less than two months later Ridgeback entered into a collaboration with pharmaceutical giant Merck, which took over the clinical development and manufacturing of molnupiravir.

U.S. federal agencies funded the research made at Emory

In a recent interview, Ridgeback co-founder Wendy Holman stated that their company asked for but “never got government funding […]” to build manufacturing capacity around molnupiravir. Although she was specifically referring to manufacturing subsidies, that statement appears to be part of an effort to minimize the extensive U.S. government funding towards molnupiravir. Her company have also been omitting the role of the U.S. government for instance in press releases, where they have instead added phrases like “[s]ince licensed by Ridgeback, all funds used for the development of molnupiravir have been provided by Merck and by Wayne and Wendy Holman of Ridgeback.”

Simply stating that Ridgeback and Merck have been developing molnupiravir with their own funding neglects the fact that when both companies entered the picture Emory had already spent over six years researching this drug with U.S. government money. The first steps in the development of molnupiravir relied upon millions awarded by U.S. federal agencies to Emory. In particular, Emory benefited from four contracts awarded by the DTRA and the National Institute of Allergy and Infectious Diseases (NIAID). These contracts were: HDTRA113C0072 worth $499,792, awarded in September 2013; HDTRA115C0075 worth $9,766,440, awarded in September 2015; HHSN272201500008Cworth $3,360,106, awarded in June 2015 by the NIAID; and 75N93019C00058, awarded in September 2019 by the NIAID with a value of $15,891,151 at signing.

While those four contracts had a combined value of $29,517,489, the development of molnupiravir also benefited from additional funding through other sources. In fact, according to journal articles reporting findings about this drug the non-clinical experiments were also funded with several NIH grants including 5U19AI109680, 1U19AI142759, 5R01AI132178, R01AI108197, F31AI133952, T32AI112541, and DK065988. Probably taking those grants into account, George Painter himself estimates that in the 2013-2020 period federal agencies invested $35 million to research molnupiravir.

The U.S. government has rights in molnupiravir patents

One consequence of the extensive funding from federal agencies towards molnupiravir is the fact that the U.S. government has rights in key patents related to this drug.

Emory has five published U.S. applications directed to derivatives of n4-hydroxycytidine, the molnupiravir parent compound. Table 1 below summarizes those U.S. patent applications. The five applications name Emory scientist George Painter as one of the co-inventors. The Painter et al. applications disclose compound formulas, manufacturing processes, and methods of using certain n4-hydroxycytidine derivatives to treat diseases. One of the Painter et al. applications specifically discloses molnupiravir in one of the claims. That patent application also claims methods of treating “a human coronavirus infection” using molnupiravir.

Another application, 20210252033, discloses methods of using molnupiravir to treat SARS-CoV-2 specifically. That application, first filed in February 2020, is still pending.

Table 1. Emory U.S. patent applications directed to N4-hydroxycytidine derivatives 

publicationGOVTfile dateprioritystatuspatent id

All of the applications listed in Table 1 acknowledged government funding, either at the time of filing or via a subsequent amendment. Specifically, each of the Painter et al. applications acknowledge one or several of the contracts awarded by the DTRA and the NIAID. Moreover, on May 18, 2020, Emory executed respective confirmatory licenses to the DTRA and NIAID stating that the compounds and methods claimed in the 20200276219 application are subject inventions under 35 U.S.C. 200, et seq, the legal provisions pertaining to the Bayh-Dole Act. This means that the U.S. government co-owns molnupiravir and has rights to demand availability at a reasonable price.

The Biden Administration has leverage to address excessive pricing 

Perhaps one of the reasons why Ridgeback  is minimizing the role of the U.S. government in the development of molnupiravir is to avoid demands to make the drug available at a reasonable price. That kind of move has worked for companies like Novartis in the past. Yet, as a promising oral pill with many potential generic suppliers, the availability and affordability of molnupiravir will likely face intense scrutiny in the upcoming months.

Harvard and King’s College researchers Melissa Barber and Dzintars Gotham recently estimated the cost of production for molnupiravir. Based on a previously developed algorithm and public information they concluded that the cost of producing molnupiravir’s active pharmaceutical ingredients, including a 10% profit margin, is $19.99 a course.

In June 2021, Merck announced an agreement to supply the U.S. government approximately 1.7 million courses of molnupiravir for approximately $1.2 billion. KEI has obtained a copy of this contract, which is discussed in another blog published today. According to the contract, the U.S. government will pay $712 dollars per unit of molnupiravir, about 35 times the cost of production as estimated by Barber and Gotham.

With government rights in all of the Emory molnupiravir patent applications published to date, the Biden Administration has leverage to ensure that the prices for molnupiravir are reasonable. This is true even if Merck or other parties receive additional patents, because the U.S. government can use the world wide royalty free right in the granted patents in any compulsory licensing case under 28 U.S.C. 1498, to limit the liability of the U.S. government to compensate patent holders.

This leverage can be used to negotiate a better price in future supply agreements.

Posted in Uncategorized | Tagged , , , , , | Leave a comment

Merck and Singapore sign deal on COVID-19 antiviral pill

Source: Reuters

SINGAPORE, Oct 6 (Reuters) – Pharmaceutical company Merck announced on Wednesday a supply and purchase agreement with Singapore that will ensure it access to its experimental oral COVID-19 antiviral drug, the latest Asian country aiming to get supplies.

The drug Molnupiravir is designed to introduce errors into the genetic code of the coronavirus and would be the first oral antiviral medication for COVID-19. Merck is seeking approval from the U.S. Food and Drug Administration for the pill.

Singapore’s health ministry confirmed the deal though it declined to comment on the number of doses it purchased, citing commercial sensitivities.

The ministry said molnupiravir would be available for use after Merck, also known as MSD Pharma in Singapore, submitted data to the Health Sciences Authority (HSA) and gets authorisation for use in Singapore.

“The addition of molnupiravir to our portfolio of COVID-19 therapeutics ensures that we have a range of treatment options for different patient groups,” the ministry told Reuters in an email.

There is no molnupiravir clinical trial in Singapore, it added.

Australia has also bought the Merck pill, while Thailand, South Korea, Taiwan and Malaysia have been in talks to buy it. The Philippines hopes its trial of the pill would allow it access.

The rush to order the drug comes after data from interim clinical trials released on Friday indicated it could reduce by about 50% the likelihood of hospitalisation or death for patients at risk of severe COVID-19.

Singapore reported a record 3,486 new coronavirus cases on Tuesday as it deals with its biggest outbreak of the pandemic.

It has vaccinated 83% of its people against COVID-19.Reporting by Chen Lin; Editing by Martin Petty, Robert Birsel

Posted in Access to Medecines, Access to Medicins, COVID-19, Diseases/Therapies, Generics, India | Tagged , , , , | Leave a comment


Source: TheIntercept

The Covid-19 treatment molnupiravir was developed using funding from the National Institutes of Health and the Department of Defense.

A FIVE-DAY COURSE of molnupiravir, the new medicine being hailed as a “huge advance” in the treatment of Covid-19, costs $17.74 to produce, according to a report issued last week by drug pricing experts at the Harvard School of Public Health and King’s College Hospital in London. Merck is charging the U.S. government $712 for the same amount of medicine, or 40 times the price.

Last Friday’s announcement that the new medicine cut the risk of hospitalization among clinical trial participants with moderate or mild illness in half could have huge implications for the course of the coronavirus pandemic. Because it’s a pill — as opposed to monoclonal antibodies, a comparable antiviral treatment that is administered intravenously — molnupiravir is expected to be more widely used and, hopefully, will cut the death rate. In the first 29 days of the trial, no deaths were reported among the 385 patients who received the drug, while eight of the people who received a placebo died, according to the statement put out by Merck and Ridgeback Biotherapeutics, the two companies that are jointly launching it.

In addition to having huge implications for health, the pill could bring staggering profits to both Merck and Ridgeback Biotherapeutics. A small Miami-based company, Ridgeback licensed the medicine from Emory University in 2020 and two months later sold the worldwide rights to the drug to Merck for an undisclosed sum. Although Ridgeback remains involved in the development of the drug, some have described the deal as “flipping.”

Like the vast majority of medicines on the market, molnupiravir — which was originally investigated as a possible treatment for Venezuelan equine encephalitis — was developed using government funds. The Defense Threat Reduction Agency, a division of the Department of Defense, provided more than $10 million of funding in 2013 and 2015 to Emory University, as research done by the nonprofit Knowledge Ecology International has revealed. The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, also provided Emory with more than $19 million in additional grants.

Yet only Merck and Ridgeback will reap the profits from the new antiviral, which according to Quartz could bring in as much as $7 billion by the end of this year. After the announcement of the encouraging clinical trial results on Friday, Merck’s stock price climbed, while stock prices of some vaccine makers sagged. Despite its initial investment, the U.S. government seems to be facing a steep markup in prices. In June, the government signed a $1.2 billion contract with Merck to supply 1.7 million courses of the medication at the $712 price. The transaction is due to take place as soon as molnupiravir receives emergency use authorization from the Food and Drug Administration.

Reasonable Terms

Good government advocates are pointing out that because federal agencies spent at least $29 million on the drug’s development, the government has the obligation to ensure that the medicine is affordable. “The public funded this drug, and therefore the public has some rights, including the rights you have it available under reasonable terms,” said Luis Gil Abinader, senior researcher at Knowledge Ecology International.

In an interview on CNBC, Ridgeback co-founder Wendy Holman noted that the company asked for but “never got government funding” to help manufacture molnupiravir. A whistleblower complaint filed by Rick Bright, the former director of the Biomedical Advanced Research and Development Authority, or BARDA, in May 2020, described Ridgeback’s unsuccessful efforts “to secure approximately $100 million” from BARDA to develop the drug as a Covid-19 treatment. The company’s press release about the study results also noted that “since licensed by Ridgeback, all funds used for the development of molnupiravir have been provided by Merck and by Wayne and Wendy Holman of Ridgeback.”

Abinader was critical of Ridgeback’s failure to acknowledge the government’s initial investment in the drug before the company acquired it. “What they want to do, apparently, is to shape the narrative about who paid for the development of this drug in order to avoid demands from the public to make it available at reasonable prices,” he said.

In an emailed response to questions submitted to Ridgeback Biotherapeutics for this article, Davidson Goldin wrote, “Ridgeback has never received any government funding for molnupiravir and self-funded the development of this medicine for treating SARS-CoV-2 when the government did not provide financial support.” Merck did not respond to inquiries about this article.

No Strings Attached

Merck has promised to make molnupiravir accessible around the world and has already entered into licensing agreements with five Indian companies that manufacture generic drugs. “Merck has committed to providing timely access to molnupiravir globally, if it is authorized or approved, and plans to implement a tiered pricing approach based on World Bank country income criteria to reflect countries’ relative ability to finance their health response to the pandemic,” the company said in its announcement of the trial results on Friday. Indian companies are planning to price the drug at less than $12 for a five-day course, according to recent reports.

In the U.S., and likely in many upper-middle-income and all high-income countries, the price will be determined by the market. Noting that the treatment may be offered to people who are not yet severely sick with Covid-19, health advocates fear that will mean some in these countries will not be able to afford the new drug. “Offering someone a $700 treatment when they don’t yet feel that ill is going to mean that a lot of people are not going to take it,” said Dzintars Gotham, a physician at King’s College Hospital in London and a co-author of the report on the pricing of molnupiravir. According to the report, pricing molnupiravir at $19.99 would allow a company a 10 percent profit margin.

Melissa Barber, a doctoral candidate at the Harvard School of Public Health and co-author of the report on molnupiravir, said that, while its pricing is not as extreme as that of some other drugs, it will likely still place the antiviral out of reach of some who could benefit from it. “If you can’t afford medicine because it’s 1,000 times more than you can afford, or because it’s 100 times more than you can afford, it doesn’t matter,” said Barber. “Those are both bad.”

Barber and Gotham acknowledge that the $17.74 cost of producing a five-day course of the antiviral pills is an estimate but said that the algorithm they used, and have employed to estimate the production costs for hundreds of drugs, tends to result in overestimates in the long run.

Meanwhile, the prices that private companies charge for drugs tend to go up rather than down. “For all these deals that have happened for therapeutics or vaccines, the price has only increased as uncertainty has decreased,” she said. “One price is given and then, for the next sale, the price goes up. The price went up for other drugs and vaccines, so I would be very surprised if this price didn’t go up, too.”

The pricing differential should be grounds to demand a better price under the Bayh-Dole Act, according to Knowledge Ecology International’s Abinader. Bayh-Dole, passed in 1980, regulates the transfer of federally funded inventions into commercial property and allows the government to “march in” and suspend the use of patents that were developed with government funding if it determines that the products are excessively priced.

“The pressure for march-in rights around this drug is going to be huge,” predicted Abinader, who suggested that the government could use the law to lower the price of molnupiravir. “When the Biden administration negotiates another supply agreement with Merck, they should probably leverage those rights in order to get a better price,” he said.

According to Gotham, who is based in London, the short story of molnupiravir already sums up the best and the worst of the U.S. pharmaceutical system. “It’s a great coup that the American government funded some scientists to develop antivirals,” he said. “The great tragedy is that, after their great success, they just gave it away to private industry with apparently no strings attached.”

Posted in Access to Medecines, COVID-19, Diseases/Therapies, Drug prices, Drugs, Federally-funded drugs, Generic competition, Generics, India, Local Production, Public funded research | Tagged , , , , | Leave a comment

Merck’s molnupiravir will be a blockbuster drug during pandemic. What about endemic COVID-19?

The global market for oral COVID-19 antivirals will reach $6 billion after the pandemic transitions to endemic, Bernstein analyst Ronny Gal estimated. (FatCamera/Getty Images)

Source: FiercePharma

After showing a 50% reduction in the risk of hospitalization or death, Merck & Co. and Ridgeback Biotherapeutics’ molnupiravir looks on track to secure an FDA emergency use authorization and become a blockbuster earner during the pandemic. But what kind of longer-term market will the drug face once COVID-19 makes the likely shift from pandemic to endemic?

With the increasing number of people vaccinated, COVID-19 is gradually becoming more manageable. Once the public health crisis transitions to the endemic stage, the need for treatment will persist. That will leave a $6 billion global market for oral antivirals, Bernstein analyst Ronny Gal estimates.

Gal used the influenza market as the benchmark for his calculation and incorporated efficacy data from molnupiravir and COVID-19 vaccines. He now projects Merck—as the only company with positive clinical data—will take half of the endemic oral drug market, with Pfizer and Roche potentially sharing the rest if their contenders prove successful.

Molnupiravir’s 50% reduction in hospitalization and death risk came from the MOVe-OUT study in high-risk, unvaccinated adults. That profile description only matches about 15% of the U.S. population, Gal noted. Merck may argue that vaccinated, high-risk patients should also be eligible for molnupiravir, but, given the impressive protection already offered by the vaccine, the drug will have a hard time making that case, Gal said.

RELATED: Merck’s oral COVID-19 antiviral slashes hospitalizations, prevents deaths in phase 3, sparking race to file with FDA

However, Pfizer and Roche are running their trials differently, which could open up a broader market for oral antivirals. Pfizer has two studies for PF-07321332, used in combo with AbbVie’s HIV antiviral Norvir. One is similar to MOVe-OUT in high-risk patients to measure reduction in hospitalization or death. The other is in low-risk patients and evaluates alleviation of COVID symptoms as the primary endpoint. By comparison, Roche’s Atea Pharmaceuticals-partnered AT-527 is in phase 3 testing in a broader non-hospitalized population regardless of risk factors, and it’s also using improvement of symptoms as the primary goal.

Using Roche’s newer influenza drug Xofluza as an example, Gal suggested that Pfizer and Roche’s symptom alleviation trials have a relatively low efficacy bar to cross and gain approval.

Because vaccination have already significantly lowered hospitalization rate, “we believe the oral antivirals will be used broadly based on symptom alleviation and shortening of disease durations,” Gal wrote in an investor note Wednesday.

RELATED: Merck and Ridgeback’s molnupiravir will be ‘complementary, but not a competitor’ to COVID-19 vaccines: analyst

In the U.S., influenza causes about 10 million to 15 million medical visits each year, accounting for about 30% of symptomatic cases, and about 80% of them eventually get a script for an antiviral, mostly Roche’s Tamiflu or its generic. 

All told, Gal assumed a slightly higher penetration of treatment for COVID than influenza, estimating 40% of all symptomatic COVID infections will be treated with an oral antiviral.

Then the question is the overall number of diagnosed cases. Compared with the high, 90% effectiveness of COVID vaccines, influenza vaccines are much less effective at 40% or below and are adopted less. But the coronavirus is much more infective than influenza. Taking these factors together, Gal’s team figures there would be about 60% as many COVID infections a year as there are flu infections. So that would translate into about 18 million overall COVID cases in the U.S. each year.

RELATED: Buyers clamor for Merck’s COVID-19 antiviral molnupiravir, but pricing is already controversial

In terms of pricing, Merck already has a deal with the Biden administration to supply 1.7 million courses of molnupiravir to the U.S. government for $1.2 billion. That’s about $700 per course. Merck said it expects to make 10 million courses of the drug by the end of 2021, meaning $7 billion in revenue.

Even though that’s the pandemic price before the data readout, Gal argued that the sticker will likely be kept same for the postpandemic world. As for Roche and Pfizer, Gal expected they will adopt a lower, $300-per-treatment price for their drugs, given they could have broader labels. It would still be a nice price; Xofluza costs about $150 after showing about a one-day improvement in time to symptom relief, Gal noted.

All told, Gal estimates a $6 billion global market for oral antivirals beginning in 2023. Of those, Merck could take away $3 billion, and Roche and Pfizer will split the remainder. Gal assigned the two latecomers lower market share at the moment after adjusting for the risks of failure.

Posted in Access to Medecines, Access to Medicins, COVID-19, Diseases/Therapies, Drug prices, Drugs, Generics, India, Uncategorized | Tagged , , , , | Leave a comment

Explained | Molnupiravir, Merck’s new drug to treat COVID-19

Source: The Hindu

Data shows drug halves chances of hospitalisation in patients with mild to moderate disease.

Pharmaceutical major Merck and Ridgeback Biotherapeutics announced via a press release on October 1 the early results from Phase-3 trials that its anti-viral drug molnupiravir halved the chances of hospitalisation in COVID-19 patients with mild or moderate disease.

Placebo trials involve testing a drug on thousands of people, in which some of them get the drug and some — who are in a placebo group — do not. In the placebo arm, 53 patients of 14% were either hospitalised or had died, whereas in the group that got the drug, 28 — or 7.3% — were hospitalised or succumbed to the infection.

After 29 days of monitoring, no deaths were reported in patients who received molnupiravir, as compared to eight deaths in those who received placebo.

Several noted clinicians have said that these are promising results, and what is particularly encouraging is that molnupiravir is a pill, unlike other drugs — with similar efficacy — used in COVID-19 treatment, which needs to be administered intravenously.

Gilead Sciences, the makers of Remdesivir, too have recently reported better data, compared to last year, on the efficacy of their treatment in mild to moderate COVID-19 patients, but it continues to be an intravenous medicine.

Is molnupiravir a breakthrough for COVID-19 treatment?

While the hospitalisation-avoidance rates are reassuring, there is still much that is unknown about molnupiravir. Complete phase-3 trial data is pending, a publication in a peer-reviewed medical journal is awaited that will explain the process of the trial in the degree of detail that will inspire more confidence among practitioners and drug authorities everywhere.

The company will soon be submitting data to the United States Food and Drugs Administration for a review, after which the drug may be approved for emergency use authorisation. So far, it being a drug that can be administered as pills as part of a five-day regimen is its biggest strength.

The drug has so far been tested only in patients with mild-to-moderate COVID-19, had started treatment within five days of testing positive and had at least one risk factor that increased their risk for severe disease. These include obesity, older age (>60 years), diabetes mellitus and heart disease.

Another positive factor is that recruitment for the phase-3 trial, that originally envisaged recruiting 1,500 patients for testing the drug’s potency, was halted early by an independent data monitoring committee because the data appeared so encouraging that it would be unethical to delay making the drug more widely available.

About 40% of participants had their genomes sequenced to detect the specific variant they were affiliated by and molnupiravir reportedly demonstrated “consistent efficacy” across viral variants Gamma, Delta and Mu.

Adverse events in molnupiravir and placebo groups were 35% and 40%, respectively and incidence of drug-related adverse events were 12% and 11%, respectively. Fewer subjects discontinued study therapy due to an adverse event in the molnupiravir group (1.3%), compared to the placebo group (3.4%).

How does molnupiravir work?

The company name for molnupiravir is ‘EIDD 2801’ the ‘E’ indicating it was developed at Emory University. Antiviral drugs, and this includes the much-in-demand Remdesivir, work by inhibiting the process by which the virus replicates. In the case of molnupiravir, when tested on cultured cells, it works by altering critical enzymes that are necessary for the virus to begin replicating in the body’s host cells.

A key challenge has been that many such antivirals, following a similar mechanism, are not effective as oral pills. However, the Merck pill reportedly appears to have overcome this barrier and adds to its promise as a ‘game-changing’ pill amid the COVID-19 crisis.

Dean Li, Merck’s head of research and development, told medical news website Statnews that the name molnupiravir was also a tangential reference to the weapon of Thor, who is one of the Avengers and a fictional hero of the Marvel Comics Universe. Thor’s hammer is called Mjolnir. “This is a hammer against SARS-CoV-2 regardless of the variant,” said Li. The suffix ‘-avir’ is a common one used for anti-viral drugs

What are the next steps for the drug?

Presumably on the back of encouraging data from Phase-1 and Phase-2 trials, Merck has reportedly begun production of the drug in large numbers. In its statement, it said it expected to produce 10 million courses of treatment by the end of 2021, with more doses expected to be produced in 2022.

Earlier this year, Merck entered into a procurement agreement with the U.S. government, under which Merck will supply approximately 1.7 million courses of molnupiravir to the U.S. government, upon EUA or approval from the U.S. FDA.

The New York Times reports that a course of treatment for the drug could cost $700 (₹50,000 approx.). This is cheaper than the monoclonal antibody therapy, which while being more effective, is a more involved treatment and is not as convenient as popping a pill. Though vaccine availability has improved, hundreds continue to die every day — some despite vaccination — and so an effective drug continues to be very much in demand.

Additionally, Merck has entered into supply and purchase agreements for molnupiravir with other governments worldwide, pending regulatory authorisation, and is currently in discussions with other governments. It is also in talks with generic drug manufacturing companies in 100 low and middle companies to accelerate production.

molnupiravir is also being evaluated for whether it can help prevent transmission of virus, or as prophylaxis, in MOVe-AHEAD, a global, multicentre, randomised, double-blind, placebo-controlled Phase-3 study, which is evaluating the efficacy and safety of molnupiravir in preventing the spread of COVID-19 within households.

Posted in COVID-19, Drug prices, Drugs, Generics, India, Uncategorized | Tagged , , , , | Leave a comment

Whose intellectual property is Bharat Biotech’s publicly funded Covaxin? India deserves an answer

If it turns out that the ICMR or the government owns the rights, the Indian public has the right to know how these were leveraged during a pandemic.

Source: Scroll

On Saturday, the pharmaceutical company Bharat Biotech officially announced the sale prices for its Covid-19 vaccine, Covaxin. State governments will have to pay Rs 600 per dose while private hospitals will have to pay Rs 1,200 per dose. These prices, fixed far above the corresponding rates announced by the Serum Institute of India for its vaccine, Covishield, has surprised observers for many reasons.

The Serum Institute could cite royalty payments to the Swedish-British firm AstraZeneca from which it has licensed its vaccine as a potential reason for higher prices. But Bharat Biotech does not have to pay any royalty for Covaxin. Covaxin is, in large measure, a product of publicly funded research in India.

It is based on the SARS-CoV-2 strain, which was isolated in the National Institute of Virology in Pune. This institute functions under the Indian Council for Medical Research. The ICMR had transferred this strain to Bharat Biotech for development and manufacture.

statement from the ICMR on May 10, 2020, had explained the collaboration in the following words:

“Work on vaccine development has been initiated between two partners. ICMR-NIV will provide continuous support to BBIL [Bharat Biotech] for vaccine development. ICMR and BBIL will seek fast-track approvals to expedite vaccine development, subsequent animal studies and clinical evaluation of the candidate vaccine, which will be fully indigenous to India.”

An ICMR official told the media, “ICMR and BBIL are jointly working for the pre-clinical as well as clinical development of this vaccine.” The ICMR also announced that it had selected 12 institutes to conduct clinical trials of the vaccine.

These are the only details available in the public domain on the collaboration between the ICMR and Bharati Biotech, but they demonstrated that Covaxin is the product of a close collaboration between the two entities.

However, we do not know anything yet about the extent of public investment in basic research, isolating the SARS-CoV-2 strain and other related interventions. As such, one is unable to gauge the share of public investment in the total amount spent to design, develop and manufacture the vaccine.

But there are a few other indicators that tell us that the ICMR’s involvement and control in developing the vaccine was indeed considerable. First, on July 3, the contents of a letter written by ICMR Director General Balaram Bhargava to the institutions managing the clinical trials, with a copy marked to Bharat Biotech, was reported in the press.

The letter said:

“It is envisaged to launch the vaccine for public health use latest by 15th August 2020 after completion of all clinical trials. BBIL [Bharat Biotech International Limited] is working expeditiously to meet the target, however, final outcome will depend on the cooperation of all clinical trial sites involved in this project.”

The letter warned:

“Kindly note the non-compliance will be viewed very seriously. Therefore, you are advised to treat the project on highest priority and meet the given timelines without any lapse.”

Clearly, the government of India was interested in hastily releasing Covaxin on Independence Day 2020 even before it completed even the basic clinical tests. It was applying pressure on the partner institutions, including Bharat Biotech, to complete their tasks before a fixed date.

Many questions

On what authority did the ICMR director general write such a letter? Surely, the ICMR must have had some control over the processes leading up to the development of the vaccine. What was the exact nature of that control? Unfortunately, we do not know.

Secondly, on April 17 this year, the government of India allowed three new firms to produce Covaxin, including the Haffkine Institute in Mumbai. On what authority did the government of India provide licences to produce Bharat Biotech’s Covaxin to these entities? Was it a simple administrative approval from the government or was it a letter of permission from the owner of the vaccine’s intellectual property rights?

Surely, the government of India had some authority to give such an approval, especially when it had not invoked any provisions of compulsory licensing. What was that authority? Unfortunately, we do not know.

In sum, opacity marks the contracts and agreements surrounding the ICMR’s relationship with Bharat Biotech. There is no information in the public domain on who owns the intellectual property rights for Covaxin. In an important article on the subject, Anupriya Dhonchak and Anik Bhaduri ask this precise question.

They cite the provisions of the Union government’s General Financial Rules, 2017, for funding sponsored projects or schemes. The rules state that on the completion of the projects “…a stipulation should be made in such cases that the ownership in the physical and intellectual assets created or acquired out of such funds shall vest in the sponsor”. What was the stipulation in the contract between the ICMR and Bharat Biotech? Unfortunately, we do not know.

There is an indirect method we can use to judge if public money was involved in the research leading to the development of the vaccine. We could review the declarations of financial support in the research papers published on the vaccine till now. According to Bharat Biotech, there have been six international peer-reviewed journal publications on Covaxin till now. A summary of these six publications and the financial acknowledgements listed are given in the table below.

On reviewing these papers, we find that in four out of the six papers, financial support from either the Ministry of Health and Family Welfare or the National Institute of Virology, Pune, or the ICMR is clearly acknowledged. All the six papers were co-authored by scholars from Bharat Biotech and the ICMR/National Institute of Virology. In five of the six papers, the ICMR Director General Balaram Bhargava was himself a co-author.

These six papers did not provide any information on the amounts involved in the financial supports. However, they do provide unequivocal evidence that public money was indeed spent towards the research that resulted in the successful development of the vaccine.

PublicationJournalAcknowledgement of financial support
Phase 2 Human Clinical Trial LancetSupported and funded by BB; co-authored by scholars from BB and ICMR
Phase 1 Human Clinical Trial
The LancetSupported and funded by BB; co-authored by scholars from BB and ICMR
Neutralization of UK Variant
Journal of Travel MedicineSupported and funded by Ministry of Health and Family Welfare, New Delhi and ICMR; co-authored by scholars from BB and ICMR
Hamster Efficacy Study
CelPressSupported and funded by ICMR; co-authored by scholars from BB and ICMR
Non-Human Primate Efficacy Study by BB and ICMR; co-authored by scholars from BB and ICMR
Preclinical Safety and Immunogenicity and funded by BB and ICMR; co-authored by scholars from BB and ICMR
Source: Note: All references to support from NIV, Pune, are represented as from ICMR in this table.

Given that taxpayer’s money was involved in the agreement, it is only appropriate that the Union government makes all the related documents public. If indeed the government or the ICMR holds the intellectual property rights for Covaxin, yet another question would arise. Despite the intellectual property rights being in public ownership, why was one company – Bharat Biotech – provided an exclusive licence for manufacture? Why was not non-exclusive licences provided to multiple manufacturers to produce the vaccine?

It is also important to note that Bharat Biotech later signed its own exclusive agreements with firms like Ocugen for the supply of 100 million doses of Covaxin in the United States. Does the ICMR get a share of Bharat Biotech’s profits from such arrangements if it has a stake in the intellectual property rights? Unfortunately, we do not know.

Indeed, the experience with the ICMR and Bharat Biotech reminds one of the ways in which the Oxford-AstraZeneca vaccine went from being a public vaccine to a private vaccine in the United Kingdom. Reports show that 97% of the funding for the Oxford-AstraZeneca vaccine came from public sources, such as the government departments of United Kingdom, scientific institutes in the United Kingdom and United States, the European Commission and various charities. Yet, Oxford University backed out of its pledge to maintain an open licence for the vaccine and signed an exclusive licence agreement with AstraZeneca.

As is well known, AstraZeneca went on to sign another exclusive agreement with the Serum Institute of India for the same vaccine to be distributed in India under the name Covishield. Thus, the Oxford-AstraZeneca vaccine became a tool for private profiteering out of public investments

India should not allow the same fate to befall Covaxin.

The immediate step in India should be a transparent publication of all agreements and intellectual property-related information on Covaxin. The ICMR and the Ministry of Health and Family Welfare should take a lead in this matter. If it turns out that the ICMR or the government of India owns the intellectual property rights over Covaxin, the Indian public has the right to know how these intellectual property rights were leveraged for public welfare amid the pandemic.

R Ramakumar is Professor, Tata Institute of Social Sciences, Mumbai.

Posted in Access to Medecines, COVID-19, IPR, Patents, Vaccines | Tagged , , | Leave a comment

[Economic Times] White House considering supporting India, S Africa move at WTO on COVID vaccines: Report

Originally Published here:

The White House is considering supporting a move by India and South Africa before the World Trade Organization on emergency temporary waiver of some Trade-Related Aspects of Intellectual Property Rights

(TRIPS) rules so that greater supplies of COVID-19 vaccines, treatment, and diagnostic tests can be produced globally, a media report has said.

Such a positive consideration by the Joe Biden administration comes after more than 60 lawmakers, mostly progressives, and a large number of rghts and non-profit pharma bodies have approached the White House to support the move of India and South Africa along with hundreds of other nations that have urgently gone to the WTO seeking a time-limited waiver of the TRIPS agreement.

The previous Trump administration had opposed such a move. The Indian Embassy here has also reached out to several lawmakers, including the members of the Indian Caucus, advocacy groups and administration in this regard. The temporary TRIPS waiver would allow countries and manufacturers to directly access and share technologies to produce vaccines and therapeutics without causing trade sanctions or international disputes.

“The White House is weighing whether to suspend intellectual property protections for Covid-19 vaccines and treatments, in response to pressure from developing nations and subsequent support from progressive lawmakers, according to three sources familiar with the matter,” CNBC news said.

According to the news report, the White House convened a meeting of deputy-level policymakers on March 22, but they reached no final decision. “The view is ‘We’re not safe until the world is safe,’ one of the sources said of the support from progressives on Capitol Hill.”

At a news conference early this month, Congressmen Rosa DeLauro, Jan Schakowsky, Earl Blumenauer, Lloyd Doggett, Adriano Espaillat, and Andy Levin urged President Joe Biden to support an emergency temporary waiver at the WTO as requested by countries led by India and South Africa.

The lawmakers said in the coming times more than 60 US representatives would collectively write to Biden to announce support for the TRIPS waiver proposed by India and South Africa at the WTO.

The temporary TRIPS waiver would allow countries and manufacturers to directly access and share technologies to produce vaccines and therapeutics without causing trade sanctions or international disputes, they said.

House Speaker Nancy Pelosi has also written a letter to Biden in this regard supporting the cause of the progressive members of her party, who now enjoy considerable influence in the Democratic Party.

CNBC said the move would allow other countries to replicate existing vaccines. The United States has so far approved three vaccine shots:

one developed by American company Pfizer and German-based BioNTech, another produced by U firm Moderna and the third made by American company Johnson & Johnson, it said.

“As part of rebuilding our alliances, we are exploring every avenue to coordinate with our global partners and are evaluating the efficacy of this specific proposal by its true potential to save lives,” USTR spokesman Adam Hodge told CNBC.

Pharma companies and the US Chambers of Commerce have opposed any move to support India and South Africa at the WTO.

Read more at:

Posted in Uncategorized | Leave a comment

International Research Organizations Support WTO TRIPS Waiver for COVID-19

Over 250 organizations and prominent researchers and experts, representing millions of researchers, educators, libraries, and support organizations globally, call for reduction of copyright barriers to COVID-19 prevention, containment and treatment

Download the full statement (PDF)

Washington, DC — For the first time today, research and education organizations around the world are joining the call for the World Trade Organization (WTO) to temporarily suspend its rules on intellectual property where needed to support the prevention, containment and treatment of COVID-19. 

Their statement, released today, calls particular attention to the need to include copyright rules within the waiver. 

Supporters of the Statement are holding an online public event and press conference Monday March 22, 9am EDT / 1pm UTC ( Register to join). 

PIJIP is sponsoring this event as part of a program of activities exploring the human right to research and its application in international copyright law and policy, supported by the Arcadia Fund’s Open Access Program . 

Leaders in education, research and copyright 

Over 100 organizations and more than 150 international academics and other experts are releasing the statement, which is being delivered to the World Trade Organization today. The signatories include the largest library and education federations in the world. The sponsors include Education International, representing over 30 million teachers globally; and the International Federation of Library Associations and Institutions (IFLA), which represents over 1,500 library and research institutions in over 150 countries. 

Download the full statement (PDF)

Read a more detailed press release with statements from supporters

Posted in Uncategorized | Leave a comment

Compulsory License instances and research synthesis

South Centre: Scope of Compulsory License and Government Use of Patented Medicines

South Centre has published a brief on various instances of compulsory licenses and government use licenses issued until March 2, 2021.

To meet public health needs, such as in the current COVID-19 emergency, governments can
use compulsory licenses and government use as a tool for procurement and import of
patented medicines.

These mechanisms are provided for in most laws worldwide. The WTO TRIPS Agreement,
as reaffirmed by the Doha Declaration on TRIPS and Public Health, recognises the right of
WTO members to grant compulsory licenses and their freedom to determine the grounds
upon which such licenses may be granted.

The South Centre Publication can be accessed here:

The table below from the above publication gives a list of compulsory licenses issued relating to COVID-19 medical technologies.

Instances of Compulsory License/Government Use License for COVID-19 related drugs

Knowledge Portal on innovation and access to medicines: Compulsory Licensing Research Synthesis

The literature on compulsory licensing in the pharmaceutical sector is rich. Although most of the literature provides information on legal provisions and discusses compulsory licensing from a theoretical perspective, knowledge portal’s research synthesis focuses on empirical studies of implementation of such licenses and their economic and political impacts, as well as on the possibilities associated with issuing compulsory licenses beyond the legal provisions contained in patent laws.

The research synthesis can be accessed here:

Posted in Uncategorized | Leave a comment

[Jacobin] Finland Had a Patent-Free COVID-19 Vaccine Nine Months Ago — But Still Went With Big Pharma

Originally posted here:

Ilari Kaila and Joona-Hermanni Mäkinen

“We felt it was our duty to start developing this type of alternative,” says professor Kalle Saksela, chair of the Department of Virology at the University of Helsinki. “Back in the spring, I still thought that surely some public entity will get involved and start pushing it forward. Turns out that no situation is urgent enough to compel the state to start actively pursuing something like this.”

Saksela’s team has had a patent-free COVID-19 vaccine ready since May 2020, which they dubbed “the Linux of vaccines” in a nod to the famous open-source operating system that also originated from Finland. The work is based on publicly available research data and predicated on the principle of sharing all new findings in peer-reviewed journals.

The research team includes some of Finland’s scientific heavyweights, such as Academy professor Seppo Ylä-Herttuala of the A. I. Virtanen Institute, a former president of the European Society of Gene and Cell Therapy, and academician Kari Alitalo, a foreign associated member of the National Academy of Sciences in the United States. They believe their nasal spray, built on well-established technology and know-how, is safe and highly effective.

“It’s a finished product, in the sense that the formulation will no longer change in any way with further testing,” Saksela says. “With what we have, we could inoculate the whole population of Finland tomorrow.”

But instead of exploring the potential of intellectual property–free research, Finland, like other Western countries, has continued to follow the default policy of the last several decades: to lean fully on Big Pharma.

In the mainstream narrative, the first-generation COVID-19 vaccines from Pfizer, Moderna, and AstraZeneca are typically presented as an illustration of how markets incentivize and accelerate vital innovation. In reality, the fact that the profit motive is the overriding force shaping medical research has been devastating — particularly in a global pandemic. The Finnish vaccine provides a striking case study of the many ways in which the contemporary patent-based funding model has slowed down vaccine development, and how it currently hampers the possibility of conducting effective mass-inoculation campaigns.

Private Intellectual Property

The need to discover the next breakthrough proprietary product has many corrosive effects on research. It incentivizes companies to conceal their findings from each other and from the wider scientific community, even at the cost of human health. The intellectual property–free “open-source” model aims to reverse this and turn research into a multilateral collaborative effort rather than a race to invent and reinvent the wheel.

When it comes to COVID-19 specifically, the stalling impact of the contemporary funding model is felt most acutely at the final stages: getting the finished product approved and into use. Whatever time was lost during the early days of the pandemic due to lack of collaboration and trade secrets, virologist Saksela points out, is relatively insignificant. In fact, the development of all first-generation COVID-19 shots has been straightforward.

“The background research was finished in an afternoon, which then set the direction for all of them,” Saksela says. “Based on what we already know about SARS-1 and MERS, it was all quite obvious — not some triumph of science.” Instead of introducing an inactivated or weakened germ into the human body, the new coronavirus shots train our immune system to respond to a “spike protein” — in itself, harmless — which forms the characteristic protrusions on the virus’s surface.

The widely shared understanding of this mechanism predates the pharmaceutical companies’ contributions. This raises questions about the impact of patent-driven research on the end product. To what extent is the work guided by medical efficacy, and how much is based on the need to retain proprietary ownership?

“Different biotech firms would slap the spike protein onto some type of delivery mechanism, whether it was RNA technology or something else,” Saksela explains. “And typically, the choice is based on what applications they have a patent on, whether it’s the best option or not.”

The Finnish vaccine uses an adenovirus to carry the genetic instructions for synthesizing the spike protein. One of its practical advantages is that, unlike with RNA technology based on lipid nanoparticles, it can be stored in a regular fridge, potentially even at room temperature. This makes for easier and cheaper delivery logistics with no requirement for ultra-cold storage. Beyond its stability and the convenience of nasal administration, the vaccine may have other superior qualities to many currently on the market, Saksela’s team believes. “In order to fully stop the virus from spreading and to get rid of new mutations, we need to induce sterilizing immunity,” meaning that the virus no longer replicates within the body of an otherwise healthy person. Preliminary animal and patient trials seem to confirm that the nasal spray accomplishes this. “With about half the people who are exposed, even if they’re symptomless, you find that the virus is still present in the upper respiratory system. So even if it’s on the way out, it still gets to run amok through the front door, making your immune system into a training partner of sorts.”

But if the vaccine is as good as advertised, what’s holding it back? Outside of Big Pharma and venture capital, few mechanisms remain to secure funding for the large-scale patient trials necessary to carry a vaccine past the finish line. Patents are state-sanctioned monopolies that hold the promise of potentially massive returns on investment. The contemporary funding model of pharmaceutical research is almost entirely pinned on that expectation, and this is where an intellectual property–free medical product runs into serious roadblocks.

A Phase III clinical trial requires tens of thousands of human subjects and would cost around $50 million. But considering that despite Finland’s relative success in controlling the virus, the country has already had to borrow an additional €18 billion ($21 billion) to get by, the sum starts to look more like a drop in the ocean — adding up to about one quarter of a percent of the pandemic-induced public debt so far. The number becomes absurdly small when contrasted with the loss of life and economic devastation around the globe.

The State Paves the Way for Private Profit

This situation is especially absurd when we consider that so-called private pharmaceutical research is itself majority public funded. Moderna received $2.5 billion in government assistance and still attempted to fleece buyers with exorbitant prices. Pfizer has boasted not having taken any taxpayer money, but the PR campaign has little to do with reality: the vaccine is based on applications of public research developed by the German firm BioNTech, which has been additionally supported by the government to the tune of $450 million.

These numbers are only the tip of the iceberg when we consider the capital that countries pour annually into universities, scientific institutions, education, and basic research. This is how the body of knowledge and know-how that underlies all innovation is built.

“For instance, we have these new types of biological drugs, related to vaccines in a technical-scientific sense, produced with the same kind of DNA technology, where the pricing is comparable to extortion,” Saksela says. “It’s very sad. Whatever is the largest sum you can extort from a person or the state dictates the cost. And of course, they’re ultimately based on publicly financed research, just as is the case with vaccines.”

In other words, we are paying for the same shot twice: first for its development, then for the finished product. But there might be even a third price tag, since governments have agreed to assume responsibility for the potential side effects of coronavirus shots. This is a typical dynamic between large corporations and states: profits are private, risks are socialized.

“And yet, when I’ve tried to advocate for Finland to develop its own vaccine, this is the main argument I’ve kept hearing: that you need to have an entity with broad enough shoulders to take on the risk,” Saksela says. “But that’s all empty talk, turns out, since the companies are demanding, and receiving, freedom from any liability.”

The current patent monopoly–based system is a relatively recent development, not some unavoidable side effect of capitalism. Until as recently as the late 1940s, governments primarily funded medical research, while the role of pharmaceutical companies was confined mostly to manufacturing and selling drugs. Nowadays, governments support companies in the form of various subsidies and monopolistic privileges.

The damage goes well beyond shortages and high prices. For one, stopping a disease in its tracks is bad business. In one famous instance, the biotech company Gilead saw its profits fall in 2015–16 as a result of its new hepatitis C drug — because it ended up fully curing most patients. The same perverse incentive structure has sabotaged efforts to create preemptive vaccines, despite urgent calls from public health experts for the last twenty years.

By investing in predictive research, the outbreak could have been stopped in China. In an interview with the New York Times, professor Vincent Racaniello of Columbia University’s Department of Microbiology and Immunology puts it bluntly: “The only reason we didn’t is because there wasn’t enough financial backing.” Disease ecologist and public health expert Peter Daszak agrees: “The alarm went off with SARS, and we hit the snooze button. And then we hit it again with Ebola, with MERS, with Zika.”

Unfortunately, there aren’t many signs yet of political leaders waking up. There is a desperate shortage of vaccines, while pharmaceutical companies struggle to keep up even with their own production estimates. This is a direct result not only of the sanctity of patents, but of how the game is rigged against solutions created outside the profit-driven system. Because vaccines can only be produced in laboratories owned or authorized by the patent holders, most of the world’s pharmaceutical factories lie idle. An emergency solution proposed by India and South Africa, backed at the World Trade Organization by a majority of the world’s governments, sought to suspend intellectual property rights on COVID-19 shots. Rich countries, led by the United States and the European Union, categorically refused.

Meanwhile, wealthy nations have made the lion’s share of all vaccine preorders. Ethics aside, this is a catastrophic way to combat a pandemic. Inadequate amounts of vaccines are being produced to begin with and distributed based on wealth rather than a sane public health policy. Even the rich countries end up shooting themselves in the foot as the virus is allowed to keep spreading and mutating over most of the globe.

Inadequate amounts of vaccines are being produced to begin with and distributed based on wealth rather than a sane public health policy.

Within this global hierarchy, Finland is among the more privileged countries. But the bottleneck in vaccine production is having an adverse effect on everyone, Finns included. As Professor Saksela emphasizes, it is crucial to start taking preparedness seriously, both on the national and global levels. The world is far from getting the current pandemic under control, and the grim fact is that the next one is only a matter of time.

“That it’s all left up to market forces is a sign of the current times,” Saksela says. “Whether that’s a wholly wise approach should at least be carefully considered.”

Social-Democratic Paradise?

Finland is often portrayed in international media as a Nordic dreamland. During the pandemic, its new left-wing government has further boosted the country’s progressive image. One might expect such a government to be the most obvious advocate of publicly financed and freely shared vaccine technology. But the last few decades — the era of neoliberalism — have cast a long shadow.

Mirroring a general trend among its counterparts, the ruling Social Democratic Party began to remodel itself in the 1990s after Tony Blair’s New Labour and the Clinton Democrats. In 2003, Finland’s national vaccine development program was discontinued, after 100 years in operation, under a Social Democratic minister of health, making way for multinational drug companies.

Though the vaccine has received much attention in Finnish media, with an opposition much more hostile to the public sector than the parties in power, there is little debate about it within the political establishment. And in lieu of direct state funding, Saksela and his partners have received advice from the Ministry of Social Affairs and Health: to establish a startup and begin courting venture capitalists.

Saksela is hopeful they might yet secure the necessary funding. But it has meant embracing, at least in part, the topsy-turvy logic of market-driven medical research: however good or lifesaving your product is, unless you intend to make money, it will be very hard to get off the ground.

“A Phase III trial will still yield intellectual property around our vaccine that we believe to be potentially profitable,” Saksela says, “even if it’s not exploitatively profitable.”

Ilari Kaila is a Finnish-American freelance writer, journalist, and composer who currently teaches at the Hong Kong University of Science and Technology and blogs at Limited Hangout.

Joona-Hermanni Mäkinen is a Helsinki-based educator and writer researching economic democracy and economic history.

Posted in Uncategorized | Leave a comment