Regeneron Submits EUA Request for REGN-COV2 Antibody Cocktail; Baricitinib/Remdesivir Combination Shows 35% Reduction in COVID-19 Mortality

As autumn and winter arrive in the Northern Hemisphere, people’s activities will increasingly shift indoors, potentially raising the risk of SARS-CoV-2 transmission. Although several candidate COVID-19 vaccines are currently in Phase 3 clinical trials, they still require time to accumulate sufficient data to demonstrate their safety and protective efficacy. Meanwhile, the development of effective therapies is crucial for saving the lives of current COVID-19 patients. Today, we examine the latest advances in the development of COVID-19 therapeutics.

Graphic by WuXi AppTec Content Team

Regeneron Submits Emergency Use Authorization Application for COVID-19 Neutralizing Antibody Combination Therapy

Neutralizing antibody therapies for SARS-CoV-2 have recently garnered significant attention. Regeneron and Eli Lilly and Company have successively announced preliminary clinical results from their respective neutralizing antibody combination therapies. Yesterday, Eli Lilly and Company announced that it had submitted an Emergency Use Authorization (EUA) application to the U.S. FDA for the investigational neutralizing antibody therapy LY-CoV555 as a monotherapy for the treatment of high-risk COVID-19 patients.

Regeneron also issued a statement yesterday, announcing that after discussions with regulatory authorities,The company has submitted an Emergency Use Authorization (EUA) application to the U.S. FDA for the use of its neutralizing antibody combination therapy, REGN-COV2, in treating patients with COVID-19.

REGN-COV2 consists of two monoclonal antibodies (REGN10933 and REGN10987) that target the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. By binding to distinct epitopes on the RBD, they block the interaction between SARS-CoV-2 and cellular receptors, thereby preventing viral entry and infection. Preclinical studies have demonstrated that these antibodies not only accelerate viral clearance but also serve as a prophylactic therapy when administered in advance, enhancing protective efficacy in animal models. Preliminary clinical trial data also indicate that, in the treatment of non-hospitalized patients with COVID-19, REGN-COV2 reduces viral load and shortens the time to symptom resolution.

Regeneron pointed out that the company currently has an inventory of neutralizing antibody therapies capable of treating nearly 50,000 patients. It is expected that in the coming months, the company will produce enough neutralizing antibody therapies to treat 300,000 patients.

JAK Inhibitor/Remdesivir Combination Reduces Mortality in COVID-19 Patients

Eli Lilly and Incyte Announce Latest Results from the ACTT-2 Clinical Trial Evaluating the JAK Inhibitor Baricitinib in Combination with Remdesivir for the Treatment of Patients with COVID-19. Previously reported results demonstrated that baricitinib met the trial’s primary endpoint, reducing the time to recovery compared with remdesivir alone.

Baricitinib, marketed under the brand name Olumiant, is a once-daily oral JAK1/2 inhibitor., it has received FDA approval for the treatment of patients with moderate to severe rheumatoid arthritis. JAK1/2 proteins mediate various inflammatory responses. Inhibition of JAK1/2 may reduce the excessive inflammatory response caused by cytokine storm in patients with COVID-19.

The latest released data show that,The combination of baricitinib and remdesivir reduced patient mortality by 35% at day 29 post-treatment compared with remdesivir alone (5.1% vs. 7.8%; HR=0.65, 95% CI: 0.39, 1.08; p=0.09).It is worth noting that combination therapy provides greater benefits in patients with severe COVID-19 who require supplemental oxygen support or high-flow oxygen therapy/non-invasive ventilation.In the subgroup of patients requiring supplemental oxygen support, combination therapy reduced mortality by 60%; in the subgroup of patients requiring high-flow oxygen therapy/non-invasive ventilation, combination therapy reduced mortality by 43%.

Eli Lilly and Company stated that researchers from its partner, the U.S. National Institute of Allergy and Infectious Diseases (NIAID), are finalizing the data analysis for this study, with the results to be published in a peer-reviewed journal in the near future. Meanwhile, the company will continue discussions with the U.S. FDA regarding the possibility of applying for an Emergency Use Authorization (EUA).

First Patient Enrolled in Phase 3 Clinical Trial of Hyperimmune Globulin Therapy

Recently, the CoVIg-19 Plasma Alliance, composed of leading pharmaceutical companies worldwide that develop plasma products, announcedSponsored by the U.S. National Institute of Allergy and Infectious Diseases (NIAID), the Phase 3 clinical trial ITAC has begun enrolling patients. This clinical trial will evaluate the safety, tolerability, and efficacy of hyperimmune immunoglobulin (H-Ig) therapy against SARS-CoV-2 in hospitalized COVID-19 patients at risk of developing severe complications. If the trial is successful, hyperimmune immunoglobulin therapy may become one of the earliest treatment options for hospitalized COVID-19 patients.

The blood of patients who have been infected with and recovered from the novel coronavirus contains neutralizing antibodies against the virus. Therefore, convalescent plasma can serve as a treatment option for patients with COVID-19. Hyperimmune globulin represents a further advancement over convalescent plasma. Manufacturers pool plasma collected from numerous recovered patients, inactivate any viruses present through rigorous procedures, and enrich the antibody content. Compared with convalescent plasma,Hyperimmune globulin offers the following advantages:

• Hyperimmune globulin has a shelf life of up to 24–36 months, making it easier to distribute and store for use in future disease outbreaks.

• All hyperimmune globulin products undergo at least three dedicated steps for viral inactivation or removal, and they can be administered to patients without the need for blood type matching.

• Hyperimmune globulin is purified and enriched during the manufacturing process, ensuring consistent high antibody levels in each dose of the product.
  

This global, multicenter, randomized, double-blind, placebo-controlled clinical trial is expected to enroll 500 adult patients. These patients are hospitalized for COVID-19 treatment, have had symptoms for less than 12 days, and do not exhibit life-threatening organ dysfunction or failure. As part of standard care, patients will receive remdesivir, and hyperimmune globulin therapy will be combined with remdesivir to evaluate its safety and efficacy. CSL Behring, Takeda, and two other companies will provide the hyperimmune globulin for the clinical trial on behalf of the CoVIg-19 Plasma Alliance.

“Since we launched this project, we have reached the critical milestone of enrolling patients in a Phase 3 clinical trial within just a few months. This strongly demonstrates the collaboration, determination, and innovation of the entire biomedical community in the fight against COVID-19,” said Ms. Julie Kim, Co-Lead of the CoVIg-19 Alliance and President of Plasma-Derived Therapies at Takeda. “This study will help us understand how hyperimmune globulin can become an important potential therapeutic option. To support our efforts, we encourage all individuals who have recovered from COVID-19 to donate their plasma, which contains vital antibodies that combat the disease and can help other patients recover more quickly.”

Note: This article is intended to introduce medical and health research and does not constitute a recommendation for treatment plans. For guidance on treatment options, please consult a reputable hospital.

References:

[1] Statement on REGN-COV2 Emergency Use Authorization Request. Retrieved October 8, 2020, from https://newsroom.regeneron.com/static-files/6feab76b-176d-402d-bf30-d40462e68b7b

[2] Baricitinib has Significant Effect on Recovery Time, Most Impactful in COVID-19 Patients Requiring Oxygen. Retrieved October 8, 2020, from https://investor.lilly.com/news-releases/news-release-details/baricitinib-has-significant-effect-recovery-time-most-impactful

[3] First Patient Enrolled in NIH Phase 3 Trial to Evaluate Potential COVID-19 Hyperimmune Medicine. Retrieved October 8, 2020, from https://www.prnewswire.com/news-releases/first-patient-enrolled-in-nih-phase-3-trial-to-evaluate-potential-covid-19-hyperimmune-medicine-301148902.html