Roche Announces EMA CHMP Positive Scientific Opinion for Casirivimab and Imdevimab Antibody Cocktail in Mild-to-Moderate COVID-19

Compiled by Keke

On February 26, Roche announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) had issued a scientific opinion supporting the use of the investigational antibody cocktail therapy casirivimab and imdevimab as a treatment option for patients with confirmed COVID-19, including those who do not require supplemental oxygen and those at high risk of progressing to severe COVID-19.

Roche stated that the scientific opinion of the CHMP (pursuant to Article 5(3) of Regulation (EC) No 726/2004) provides a harmonized EU view on the efficacy, quality, and safety of casirivimab and imdevimab. This review was conducted in parallel with the EMA’s ongoing rolling review process, which is used to accelerate the formal assessment of marketing authorization applications for promising medicines during public health emergencies. Under Article 5(3), the CHMP evaluated available data in patients with COVID-19, including data from the REGN-COV2067 trial as well as supportive data from other studies.

Roche and Regeneron are collaborating to develop, manufacture, and distribute casirivimab and imdevimab to patients worldwide, with the goal of providing more than 2 million doses of this therapy in 2021. Regeneron will be responsible for distributing this antibody cocktail therapy in the United States, while Roche will handle distribution outside the United States; the first batches of Roche-manufactured formulations are already being distributed. Casirivimab and imdevimab can provide a much-needed treatment option for individuals who have already developed symptoms of COVID-19, and may prevent infection in people exposed to the virus, holding promise to help slow the spread of the global COVID-19 pandemic.

Meanwhile, the investigational antibody cocktail of casirivimab and imdevimab continues to be evaluated in multiple clinical trials involving patients with COVID-19, such as those conducted in non-hospitalized patients and certain hospitalized patients, including the open-label RECOVERY trial in hospitalized patients in the UK, as well as trials assessing its efficacy in preventing COVID-19 among household contacts of infected individuals. As of February 2021, approximately 23,000 participants had enrolled in clinical trials of this cocktail therapy. Lower doses of casirivimab and imdevimab are also under investigation, with the aim of expanding the number of patients who can potentially be treated.

Regarding the review conducted by the CHMP under Article 5(3) of Regulation (EC) No 726/2004, Roche explained that the purpose of the referral procedure under Article 5(3) is to enable the CHMP to formulate a unified scientific opinion on the quality, safety, and efficacy of medicinal products at the EU level, based on currently available data. These scientific opinions may be taken into account by EU Member States when making decisions on the use of medicinal products at the national level, prior to the formal issuance of marketing authorization.

The review under Article 5(3) of Regulation (EC) No 726/2004 was initiated by the EMA Executive Director following preliminary discussions with the EMA Pandemic Task Force (COVID-ETF), which brings together experts from across the European medicines regulatory network to provide recommendations on the development, authorization, and safety monitoring of COVID-19 medicines and vaccines.

Casirivimab and imdevimab are a cocktail of two monoclonal antibodies (known respectively as REGN10933 and REGN10987), designed by Regeneron scientists to block the infectivity of SARS-CoV-2, the virus that causes COVID-19. They evaluated thousands of fully human antibodies generated by the company’s proprietary VelocImmune® mice, which are genetically engineered to possess a human immune system, as well as antibodies identified from humans who had recovered from COVID-19.

The two potent virus-neutralizing antibodies, casirivimab and imdevimab, are believed to bind in a non-competitive manner to the key receptor-binding domain of the viral spike protein, thereby hypothetically reducing the ability of variant viruses to evade treatment and providing protection against spike mutations that may emerge in the population.

In November 2020, the U.S. FDA approved this antibody cocktail under Emergency Use Authorization (EUA) for the treatment of adult and pediatric patients (aged 12 years and older, weighing at least 40 kg) with mild-to-moderate COVID-19 who tested positive for SARS-CoV-2, as well as those at high risk of progressing to severe COVID-19 and/or hospitalization.

In addition to investing a range of R&D resources and developing multiple diagnostic products, Roche is conducting several clinical trials to evaluate the efficacy and safety of Actemra (tocilizumab) in the treatment of COVID-19-associated pneumonia. These include COVACTA and EMPACTA, the first global Phase III multicenter, randomized, placebo-controlled studies sponsored by Roche to assess Actemra. The COVACTA study did not meet its primary endpoint, and Roche stated that it continues to evaluate the results. The EMPACTA study met its primary endpoint, and Roche is currently assessing whether Actemra, when added to standard of care, can offer a favorable benefit-risk profile for specific patient populations based on patient and disease characteristics.

In October 2020, Roche and Atea signed an agreement to co-develop AT-527, an oral direct-acting antiviral (DAA) currently undergoing Phase II clinical trials. AT-527 has the potential to become the first novel oral antiviral drug for the treatment of outpatients and hospitalized patients with COVID-19, as well as for post-exposure prophylaxis.

Reference source: EMA issues advice on casirivimab and imdevimab antibody cocktail for the treatment of mild-to-moderate COVID-19