On March 18, Shanghai Fosun Pharma (Group) Co., Ltd. (hereinfollowing referred to as Fosun Pharma) announced that its holding subsidiary Shanghai Fosun Pharma Industry Development Co., Ltd. (hereinfollowing referred to as Fosun Pharma Industry) and the drug patent pool organization (hereinfollowing referred to as MPP) authorized the production of the generic version of Pfizer’s oral COVID-19 drug nirmatrelvir and the supply of nirmatrelvir/ritonavir combination packaging to 95 low- and middle-income countries covering approximately 53% of the world’s population Sign the Sublicense Agreement.
According to the content of the license agreement, MPP granted Fosun Pharma a non-exclusive sub-license to use relevant patents and know-how for the production of nematevir APIs and finished preparations, as well as the combination packaging with ritonavir (hereinfollowing referred to as this license). ). Under this license, the production facilities of related products need to be approved by SRA (Strict Regulatory Authority, that is, a strict regulatory agency, including members of the International Council for Harmonization of Technical Requirements for Human Medications (ICH), or ICH observers and regulatory agencies related to ICH members, etc.) Or qualified by the World Health Organization Prequalification (WHO PQ).
Nematevir/ritonavir combination package is a combination package of oral Covid-19 therapy for the treatment of adults with mild to moderate novel coronavirus pneumonia (COVID-19) with high risk factors for progression to severe disease. Nirmatavir (preparation) (Nirmatrelvir, namely PF-07321332) is a new coronavirus main protease (MPRO, also known as 3CL protease) inhibitor, Ritonavir (Ritonavir) is an HIV-1 protease inhibitor agents and CYP3A inhibitors. Administration in combination with low doses of ritonavir helps slow the metabolism or breakdown of nematevir, allowing it to remain active in the body for a longer period of time at higher concentrations to help fight the new coronavirus.
Pfizer’s nematevir tablet/ritonavir tablet combination packaged product (PAXLOVIDTM) received emergency use authorization from the U.S. Food and Drug Administration in December 2021 and conditional approval from the European Medicines Agency in January 2022. In February 2022, it received special approval from the Japanese Ministry of Health, Labour and Welfare, and in February 2022, it received emergency conditional approval from the China National Medical Products Administration. At present, the drug has been approved for marketing in more than 50 countries around the world.
Wu Yifang, Chairman and CEO of Fosun Pharma, said, “We are delighted to have reached an agreement with the Drug Patent Pool Organization to jointly improve the global availability of COVID-19 treatment drugs. As an enterprise that actively undertakes social responsibilities, Fosun Pharma takes innovation and research and development as the core driving force of enterprise development, and with the help of our global operation network, it is committed to solving unmet clinical needs, and strives to improve the global popularity of new crown treatment drugs. The accessibility and affordability of low-income countries or regions continue to contribute to the global fight once morest the epidemic and save more lives.
Since the global outbreak, researchers around the world have been developing a drug for COVID-19, hoping it might be taken outside the hospital to relieve symptoms, speed up recovery and avoid hospitalization, according to an early report from Sohu Medicine. However, the current COVID-19 treatment drugs must be administered intravenously or by injection, which is relatively inconvenient to use.
Pfizer said in the second half of last year that clinical studies of its candidate drug PF-07321332 showed that it might reduce the risk of hospitalization and death in patients with mild to moderate new coronary pneumonia by 89%, and hoped that the US FDA and other regulatory agencies around the world would approve the use of the drug.
On February 12, 2022, the official website of the State Drug Administration of my country issued an announcement stating that the import registration of Pfizer’s new coronavirus treatment drug neimatevir tablet/ritonavir tablet combination package (ie Paxlovid) was conditionally approved.
Who can use Paxlovid?
Paxlovid consists of nematevir and ritonavir, the former inhibits the replication of viral proteins, and the latter increases the drug concentration of the former and prolongs the action time. The drug is currently approved for the treatment of adults with mild to moderate new coronary pneumonia or children over 12 years old with high risk, such as new coronary pneumonia patients with advanced age, chronic kidney disease, diabetes, cardiovascular disease, and chronic lung disease. The drug is not approved for the treatment of hospitalized patients with severe or critical Covid-19, nor is it approved for pre-exposure or post-exposure prophylaxis of SARS-CoV-2.
The drug, taken within 3 days following the onset of symptoms, and used continuously for no more than 5 days, can reduce the risk of hospitalization or death by 89%, with few adverse reactions and good safety. Although it cannot replace vaccines, it is a guarantee of efficacy for patients with mild to moderate new coronary pneumonia.
How much is Paxlovid priced?
Last year, the U.S. government ordered 10 million doses of Paxlovid for $5.29 billion, which is estimated to be $529 per course of treatment, which is significantly lower than the cost of monoclonal antibodies, but it is also a large number. The price of drugs in each country is different. We can make a rough estimate through Pfizer’s 2021 earnings report: Paxlovid is expected to have global sales of $22 billion in 2022, so how much is each course of treatment?
What other drugs are available to treat COVID-19?
At the same time as Paxlovid, it received emergency approval from the US FDA. Molnupiravir, a subsidiary of Merck, is required to be used within 5 days following symptoms appear, and clinical reports say that it can reduce the risk of hospitalization by 50%. Some experts pointed out that the clinical trial design standards of the two drugs are different, and it is not possible to directly compare the efficacy of the two drugs. However, the latter’s hidden dangers of introducing mutations into human DNA have been questioned by many experts.
GlaxoSmithKline’s monoclonal antibody drug Sotrovimab received US FDA authorization to treat Omicron infections, and Eli Lilly’s Bebtelovimab was also re-approved. Unfortunately, the Regeneron monoclonal antibody does not seem to be effective once morest Omicron. AstraZeneca reported that its Evusheld antibody was effective once morest Omicron.
In my country, Tengsheng Biopharma announced that the combination therapy of ambavirumab/romisevirumab maintained its neutralizing activity once morest Omicron.
Compared with inpatient injection of monoclonal antibody drugs, oral antiviral drugs are more convenient to use and less expensive, but they are not approved for the treatment of critically ill hospitalized patients.
With Paxlovid, is it possible to end the COVID-19 pandemic?
First of all, the 89% effective rate provided by Paxlovid is the clinical trial data, with a total of more than 2,000 patients in the experimental group and the control group. In real-world use, for which we only found data on the use of the drug in Israel, 92% of the 850 patients who took the drug experienced symptomatic improvement and were assessed to reduce their risk of hospitalization by 90%. Further investigation and evaluation are required for the use of larger-scale regions and populations.
Compared with clinical trials, there are certain limitations in the actual application of drugs. For example, the drug is required to be taken within 5 days following diagnosis, and the typical symptoms of fever and cough related to new coronary pneumonia are very similar to those of influenza and colds, and are likely to be ignored by patients; If the test certificate can be obtained in time, or the appropriate medical institution cannot be found, treatment may also be delayed.
At the same time, the availability of medicines cannot be ignored. The 10 million doses ordered by the U.S. government will not be fully delivered until the end of June, and it is up to clinicians to judge which patients will be given priority for drug treatment. For other countries, how to obtain a steady source of medicines, and the cost of treatment of hundreds of dollars per course cannot be ignored.
The epidemic is a global problem. Only when the epidemic in all countries can be brought under control is the real end of the epidemic. In order to solve the problem of drug supply and treatment cost, Pfizer signed an agreement with the Medicines Patent Pool (MPP) organization, and generic drug companies with production licenses can provide generic drugs to 95 countries, which cover regarding 53% of the world’s population. Pfizer will not receive royalties from sales in these countries while COVID-19 is declared a “public health emergency of international concern” by the WHO. Among developing countries, China and Brazil are not included in this scope.
To end the epidemic, vaccination cannot be ignored. The FDA specifically emphasized that Paxlovid’s authorization does not include pre- and post-exposure prophylaxis, so Paxlovid is not a substitute for vaccines for individuals who are advised to receive the new coronavirus vaccine and booster doses. In contrast, in countries where the epidemic has spread widely, can mandatory quarantine restrictions be relaxed?
From the current point of view, the widespread vaccination of vaccines makes most people immune, and it is not easy to become severe following infection; many countries have reported that the risk of severe disease in Omicron is lower than that of the original strain and Delta. At this time, the popularity of oral drugs has further reduced the risk of severe disease for those with symptoms. Will the new coronavirus eventually become a virus with the same or lower risk as the flu? The United Kingdom, the United States and other countries have taken an important step towards the comprehensive liberalization of society. The actual effect of oral medicine on social liberalization is worth further observation.Return to Sohu, see more