India’s CDSCO Greenlights Emergency Use Authorization of Monoclonal Antibody Cocktail Produced by Regeneron & Distributed by Roche During Crisis

India’s CDSCO Greenlights Emergency Use Authorization of Monoclonal Antibody Cocktail Produced by Regeneron & Distributed by Roche During Crisis

First known as REGN-COV2 and now as Casirivimab and Imdevimab, Regeneron’s monoclonal antibody cocktail authorized by the U.S. Food and Drug Administration (FDA) on an emergency basis for COVID-19 patients at a high risk for disease progression or hospitalization, as well as in Europe for similar at risk COVID-19 patients not hospitalized by the Committee for the Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) is now authorized for emergency use by India’s Central Drugs Standards Control Organization (CDSCO). This process was led by Switzerland-based Roche which in August entered into a collaboration deal with Regeneron to boost supply of the cocktail monoclonal antibody. Now with India’s CDSCO action, Roche can import the globally produced product batches to the country then to be marketed and distributed in India via a partnership with the publicly traded Indian pharmaceutical company Cipla Limited. This novel therapeutic option again has demonstrated some success in America, however its not cheap to administer, requires considerable infrastructure, capacity, and the like. The authorization was based on data available in the United States and Europe.

India COVID-19 Crisis

India spent many months during the pandemic avoiding much of the impacts of the crisis. The world’s second most populous country did experience a considerable first wave as by September 16, there were a reported 97,894 cases in a day and the running seven day average per day was 93,199.

However, that waned, and from late November to early March, the cases stabilized and the country seemed in relatively good shape compared to many others. But due to a confluence of factors and forces, from a relaxation of standards (big political rallies with lots of people and no masks) and more transmissible mutant variants of the pathogen to a lack of effective planning and adjustment by government and health authorities, the situation turned outright horrific in this much larger wave of the pandemic. As of this writing, there were over 412,000 cases reported in one day with a seven day running average per day of 385,856.

A tragic situation, the human suffering’s been covered for the world to see, including the loss of family members on a daily basis. And just days ago, several stages in India ran out of vaccines, exacerbating a second wave of infections leaving hospitals and health centers, and morgues overflowing with people. All the while, families, from the rich and growing middle class to the poor, scramble for apparently scarce medicines, reported Reuters recently

It’s in this context that the Regeneron-developed product, in partnership with Roche, is material as India is the number one hot spot for the disease now and trails only the United States in total number of reported cases at 21,077,410. The death rate has been lower here compared to Brazil and the United States but much needs to be sorted out here once the crisis passes as so much more could have been done to save lives. 

The Product

TrialSite followed the development of this product with keen interest. The clinical research process got off to somewhat of a different start as there wasn’t a traditional Phase 1 trial but rather the drug was tested in hospitals during pandemic in the United States in selected hospitals under a so-called Sentinel program, pre-authorized by the U.S. FDA. The process included a Drug Monitoring Safety Board which was apparently independent and kept a watchful eye on safety signals. Regeneron secured $450 million from the U.S. government for a fixed number of bulk lots of the product, helping to cover some of the R&D and manufacturing costs.

From there, a number of trials started, including a Phase 3 nearly right after. That’s what attracted the real attention from TrialSite as it wasn’t clear how they (Regeneron) could go straight to a Phase 3 clinical trial. The level of transparency with Regeneron was notable and commendable. They answered unplanned questions promptly, which is a lot more than some other sponsors.

Casirivimab and Imdevimab are human immunoglobulin G-1 (IgG1) monoclonal antibodies produced by recombinant DNA technology and were founded using Regeneron’s advanced VelociSuite technology

Laboratory proteins that mimic the human immune system’s ability to combat SARS-CoV-2 virus, the cocktail are specifically tailored to fight the spike protein, designed to block SARS-CoV-2’s attachment and entry into human cells.   The company (Regeneron) utilized and engineered two neutralizing antibodies which bind to different parts of the spike protein making it more effective.

The investigational product (again not fully approved but under EUA) is approved at a combined dose of 1200 mg (600 mg of each drug) administered by intravenous infusion or subcutaneous route. The drug must be stored at 2°C to 8° C.

The Regeneron/Roche Deal

Back on August 19, Regeneron and Roche announced a deal that allowed Roche and Regeneron to collaborate to develop and produce the two-antibody cocktail with Regeneron, a much smaller company, concentrating on the United States while Roche would take care of rest of the world. As Roche is one of the largest and most sophisticated biologic producers, the deal purportedly was to extend overall capacity by at least three and a half times greatly increasing the number of doses available to the world.

Equitable Distribution?

In a Cipla press release, Roche conveyed that “Roche will do everything to ensure an equitable distribution across the globe, however initial local demand may far exceed the supplies the company will be able to provide.” Clearly, the supply and demand calculous covers as well for the required generation of profits which the company is always under pressure to do. TrialSite will monitor this situation to learn more about how the product is distributed within India.

The Regimen

The cocktail combination is administered for the treatment of mild to moderate COVID-19 in adults and pediatric patients 12 and up weighing at least 40 kg and who are confirmed infected with SARS-CoV-2, and importantly deemed high risk of developing severe COVID-19. In the Roche/Cipla press release, they companies define high risk as “Age = 60, Obesity, Cardiovascular disease, including hypertension—Chronic lung disease, including asthma. Also included in this category are Type 1 and type 2 diabetes, Chronic kidney disease such as those on dialysis as well as chronic liver disease. Those individuals that are immunosuppressed based on physician assessment are also considered—e.g. a cancer patient receiving organ transplantation, immune deficiencies from HIV, etc.

The investigational product may help this class of patient prior to degradation of condition. Recently, Cipla noted that a large Phase 3 global clinical trial with 4,567 high-risk, non-hospitalized COVID-19 patients revealed the drug met its primary endpoint, demonstrating that Casirivimab and imdevimab significantly reduced the risk of hospitalization or death by 70% a compared to placebo. The study results revealed that in the patient base the duration of symptoms was lessened by four days.

CIPLA Role

Cipla will market and distribute the product in India by leveraging its distribution strengths across the nation. The company said in its press release that it will work with leading hospitals and COVID-19 treatment centers to make the drug available.

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