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Regeneron Monoclonal Antibody 2023

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January 13, 2023
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Regeneron Anti-SARS-CoV-2 Monoclonal Antibody 2023

Regeneron Pharmaceuticals, Inc. revealed its intentions at the J.P. Morgan Healthcare Conference on January 9, 2023, to expand its Anti-SARS-CoV-2 Monoclonal Antibody offerings in 2023. The Company stated: in the U.S. alone, millions of immuno-compromised people will not adequately respond to vaccination. And antibodies can be dosed prophylactically to help prevent infection and severe COVID-19 disease.

Regeneron REGN14287

On January 9, 2023, Regeneron's presentation at a San Francisco CA conference included slide #27, which stated Next-gen COVID antibody binds outside variable RBD and has demonstrated high neutralization activity against all known variants and lineages. And disclosed: Anticipate initiating REGN14287 clinical trial in 2023, pending regulatory discussions. The phase 3 study clinical trial NCT04425629, was last updated on July 29, 2022.

On December 16, 2021, Regeneron issued a statement saying 'Regeneron has confirmed that multiple next generation' monoclonal antibodies from its large collection of fully human monoclonal antibodies targeting the SARS-CoV-2 coronavirus are active against the Omicron (B.1.1.529) and Delta (B.1.617.2) variants, as well as against the other variants of concern. Pending regulatory discussions, we anticipate entering the clinic in the first quarter of 2022.

Regeneron's REGEN-COV

Regeneron's REGEN-COV Anti-SARS-CoV-2 Monoclonal Antibody (Ronapreve) combines two monoclonal antibodies (mAbs), casirivimab, and imdevimab, explicitly designed to block the infectivity of SARS-CoV-2, the coronavirus that causes COVID-19. REGEN-COV was the first mAbs therapy to demonstrate an antiviral effect in patients hospitalized with COVID-19. Regeneron does not use human tissue in any of our manufacturing processes. Instead, the manufacture of mAbs starts with a mammalian cell line called the Chinese Hamster Ovary (CHO) cells. These CHO cells are then modified with a synthetic DNA sequence to direct them to make mAbs indistinguishable from human antibodies.

Regeneron core technologies enable the rapid and efficient generation of these protective antiviral mAbs outside of the body, derived from genetically humanized mice or convalescent humansRegeneron's potent, virus-neutralizing antibodies that form the REGEN-COV bind non-competitively to the critical receptor binding domain of the coronavirus's spike protein, which diminishes the ability of mutant viruses to escape treatment and protects against spike variants that have arisen in the human population, as detailed in Science, published on August 21, 2020. The resulting antibodies correspond to the most potent antiviral antibodies that could be elicited by a vaccine or exposure to a pathogen.

REGEN-COV can be delivered via injection or IV, providing 'passive immunity and immediately protecting people from COVID-19. However, it must be re-administered to remain effective over time. These mAbs can also treat an existing infection, unlike vaccines used preventatively.

The WHO announced on September 24, 2021, 'patients who are non-severe and at higher risk for hospitalization be treated and those that are severe or critical with seronegative status (those who have not developed natural antibodies against COVID-19 determined through accurate, rapid tests) be treated; as these two patient groups are the patients that stand to benefit most from the treatment.' On March 3, 2022, the WHO suggested treatment with casirivimab-imdevimab, conditional to those with seronegative status, and where viral genotyping can confirm a susceptible SARS-CoV-2 variant (i.e., excluding omicron BA.1). Treatment with casirivimab-imdevimab is in addition to the current standard of care, including corticosteroids and IL-6 receptor blockers.

The Company announced on October 14, 2021, that the FDA had accepted for priority review a Biologics License Application (BLA) for REGEN-COV to treat COVID-19 in non-hospitalized patients and as prophylaxis in specific individuals. A second BLA submission focusing on treating patients hospitalized due to COVID-19 is expected to be submitted later in 2021. The U.S. FDA issued emergency authorization on February 25, 2021. The FDA issued an updated Health Care Provider Fact Sheet for REGEN-COV on December 20, 2021, with specific information regarding expected activity against the Omicron variant (B.1.1.529/BA.1). On January 19, 2022, the U.S. NIH published an updated version of the statement that the COVID-19 Treatment Guidelines Panel addressed the dominance of the B.1.1.529 (Omicron) variant in the U.S.

The U.S. FDA revised the authorizations for REGEN-COV on January 24, 2022, to limit their use to only when the patient is likely to have been infected with or exposed to a variant that is susceptible to these treatments. Because data show that these treatments are highly unlikely to be active against the omicron variant. These treatments are not authorized in any U.S. state, territory, or jurisdiction. As of April 14, 2022, the FDA extended by three months its review of the BLA for REGEN-COV to treat COVID-19 in non-hospitalized patients and as prophylaxis in certain individuals. 

However, it remains authorized in Europe. On June 8, 2022, the EMA published a list of critical authorized medicines for the COVID-19 public health emergency.

DrugBank: DB15691; KEGG D11938D11939 Dosage and Administration (Section 2.4) and How Supplied/Storage and Handling (Section 19): updated storage temperature range and duration updated as of November 1, 2021.

Tarrytown, New York-based Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) collaborates with Roche to increase the global supply of REGEN-COV. Regeneron is responsible for developing and distributing the treatment in the U.S. Roche is primarily responsible for the development and distribution of Ronapreve outside the U.S. Regeneron's August 2021 corporate update is linked hereRegeneron's VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. This COVID-19 Antibody Cocktail's development and manufacturing have been funded partially with federal funds from the Biomedical Advanced Research and Development Authority under O.T. number: HHSO100201700020C. Corporate Fact Sheet; Form 10K.

REGEN-COV Availability

On February 7, 2022, the U.S. HHS Assistant Secretary for Preparedness and Response confirmed (0) doses of REGEN-COV would be distributed in the U.S. Since October 2021, over 1.4 million doses of REGEN-COV were shipped in the U.S. As of June 27, 2022, REGEN-COV was not available in the U.S.

On November 12, 2021, European Commission approved REGEN-COV in the U.S. and Ronapreve™ in the European Union and the U.K.Switzerland, New Zealand, and Malaysia. The Company that applied for Ronapreve authorization was Roche Registration GmbH.

REGEN-COV History

The concept that Monoclonal drug cocktails can prevent viral escape has been demonstrated for traditional antiviral drugs that treat HIV and other viruses. However, Regeneron now reports the fundamental realization that this can also be true for antibody-based therapies, as reported in a paper published in Science on August 21, 2020.

Regeneron scientists evaluated thousands of fully human antibodies produced by the Company's proprietary VelocImmune® mice, which have been genetically modified to have a human immune system and antibodies isolated from humans who have recovered from COVID-19. CDER Scientific Review Documents Supporting Emergency Use Authorizations for Drug and Biological Therapeutic Products for COVID-19 were updated by the U.S. FDA on September 9, 2021.

On September 23, 2021, the NEJM published an Original Article that concluded, 'Subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons. In addition, among the participants who became infected, in a phase 3 study, REGEN-COV reduced the duration of symptomatic disease and the duration of a high viral load.'

The NEJM published results from a phase 3 study in an Original Article on September 30, 2021, that concluded by saying 'REGEN-COV reduced the risk of Covid-19–related hospitalization or death from any cause, and it resolved symptoms and reduced the SARS-CoV-2 viral load more rapidly than placebo.' In addition, a non-peer-reviewed retrospective analysis of immunodeficient patients published on November 9, 2021, found REGEN-COV treatment was associated with rapid viral clearance and clinical improvement in the evaluable patients with long-standing COVID-19.

On November 10, 2021, a non-peer-reviewed phase 3 study reported 'asymptomatic and low-risk symptomatic SARS-CoV-2-infected outpatients seronegative for antibodies against SARS-CoV-2 at baseline. REGEN-COV significantly and comparably reduced viral load at all IV and SC doses.' Additionally, another non-peer-reviewed clinical study published on November 14, 2021, found Repeat Subcutaneous Administration of REGEN-COV in Adults is Well-Tolerated and Prevents the Occurrence of COVID-19. In total, 969 subjects were treated. Repeat monthly dosing of 1200 mg SC REGEN-COV led to a 92.4% relative risk reduction in clinically defined COVID-19.

REGEN-COV Indication

The WHO suggests treatment with casirivimab-imdevimab, conditional to those at highest risk of hospitalization, and where viral genotyping can confirm a susceptible SARS-CoV-2 variant.

REGEN-COV Women

Pregnancy: There are insufficient data to evaluate a drug-associated risk of significant congenital disabilities, miscarriage, or adverse maternal or fetal outcomes. REGEN-COV should only be used during pregnancy if the potential benefit outweighs the potential risk for the mother and the fetus REGEN-COV casirivimab and imdevimab injection therapy should be used during pregnancy only if the potential benefit justifies the mother and fetus's potential risk.

Nursing Mothers: There is no clinical experience using REGEN-COV (casirivimab and imdevimab) injection in COVID-19 patients breastfeeding. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for casirivimab and imdevimab injection and any potential adverse effects on the breastfed child from injection or the underlying maternal condition.

REGEN-COV Dosage

In the U.S., REGEN-COV can be administered by intravenous infusion (as short as 20 minutes) or subcutaneously. The authorized dosage is 600 mg of casirivimab with 600 mg of imdevimab administered together as a single intravenous (IV) infusion or by subcutaneous injection as soon as possible after a positive viral test for SARS-CoV-2 and within ten days of symptom onset. A phase 3 study supported by Regeneron Pharmaceuticals found a 1200 mg subcutaneous dose of REGEN-COV also prevented COVID-19 in household contacts of SARS-CoV-2-infected individuals.

For individuals in whom repeat dosing is determined to be appropriate for ongoing exposure to SARS-CoV-2 for longer than four weeks and who are not expected to mount an adequate immune response to complete SARS-CoV-2 vaccination, the initial dose is 600 mg of casirivimab and 600 mg of imdevimab by subcutaneous injection or intravenous infusion followed by subsequent repeat dosing of 300 mg of casirivimab and 300 mg of imdevimab by subcutaneous injection or intravenous infusion once every four weeks for the duration of ongoing exposure.

REGEN-COV Children

The EMA's Committee for medicines issued its opinion on the Company's pediatric investigation plans for casirivimab and imdevimab on October 11, 2021, which describe how the medication should be developed and studied for use in children in accordance with the accelerated timelines for COVID-19 medicines. 

REGEN-COV Packaging

REGEN-COV is available in two distinct presentations: Dose pack bags: Dose pack bags will include a sufficient number of vials of casirivimab and imdevimab to prepare multiple doses. Co-formulated solution of REGEN-COV: The co-formulated solution of REGEN-COV contains two antibodies in a 1:1 ratio in a single dose vial consisting of 600 mg casirivimab and 600 mg of imdevimab per 10 mL (60 mg/60 mg per mL). Either presentation of REGEN-COV as described above may be prepared for intravenous infusion or subcutaneous injection. The U.S. FDA published Temporary Alternative Packaging of Casirivimab and Imdevimab authorized to meet ongoing COVID-19 Public Health Demands on September 16, 2021. Medical information inquiries should be referred to Regeneron Medical Information at 1-844-734-6643.

REGEN-COV Side Effects

Clinical worsening of COVID-19 after administration of REGEN-COV has been reported. It may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmia (e.g., atrial fibrillation, tachycardia, bradycardia), fatigue, and altered mental status. The most common side effects were injection site reactions. The signs and symptoms of injection site reactions that occurred in at least 1% of subjects in the REGEN-COV group were skin redness (erythema), an uncomfortable, irritating sensation that creates an urge to scratch (pruritus), and ecchymosis (discoloration of the skin resulting from bleeding underneath, caused by bruising). There were no cases of severe hypersensitivity reactions, or potentially life-threatening allergic reactions (such as anaphylaxis), says the FDA.

Anyone can submit a report to VAERS, including parents and patients. And healthcare providers are required by law in the USA to report to VAERS.

Regeneron Inc. Financial News (NASDAQ REGN)

January 11, 2022 - Seeking Alpha reported U.S. net product sales of REGEN-COV (casirivimab and imdevimab) of ~$5.82B for FY 2021 and about $2.29B for Q4 2021.

November 4, 2021 - Regeneron Pharmaceuticals, Inc. posted better-than-expected third-quarter 2021 results, beating on earnings and sales, including $804 million attributable to REGEN-COV.

September 14, 2021 - Regeneron Pharmaceuticals, Inc. announced that the U.S. Department of Health and Human Services and the Department of Defense would purchase 1.4 million additional doses of REGEN-COV (casirivimab) imdevimab) 1,200 mg doses at the cost of $2,100 per dose. The U.S. government confirmed it would continue to provide REGEN-COV at no cost to patients. In September 2021, Regeneron expects to begin delivering the additional REGEN-COV doses to the U.S. government, with the vast majority delivered in Q4 2021.

REGEN-COV News For 2022 - 2022

June 27, 2022 - The U.S. FDA authorized an extension to the shelf-life from 24 months to 30 months for specific lots of the refrigerated Regeneron monoclonal antibodies, casirivimab and imdevimab.

April 14, 2022 - Regeneron Pharmaceuticals, Inc. announced that the U.S. FDA had extended by three months its review of the Biologics License Application (BLA) for REGEN-COV to treat COVID-19 in non-hospitalized patients and as prophylaxis in certain individuals. The extension is due to ongoing discussions with the FDA on pre-exposure prophylactic use, for which Regeneron has submitted additional data from its completed prophylaxis trial that the FDA has accepted for review. The FDA considers the submission of these additional data to be a Major Amendment to the BLA and has provided a new target action date of July 13, 2022.

October 7, 2021 - The COVID-19 Treatment Guidelines Panel recommended the use of anti-SARS-CoV-2 mAbs for the treatment of mild to moderate COVID-19 and for post-exposure prophylaxis of SARS-CoV-2 virus infection in individuals who are at high risk for progression to severe COVID-19, as outlined in the Food and Drug Administration EUAs issued for the anti-SARS-CoV-2 mAbs.

August 10, 2021 - The U.S. FDA authorized REGEN-COV2 monoclonal antibody therapy for post-exposure prophylaxis (prevention) for COVID-19.

June 4, 2021 - Regeneron Pharmaceuticals, Inc. announced the U.S. Food and Drug Administration (FDA) updated the Emergency Use Authorization (EUA) for REGEN-COV™, lowering the dose to 1,200 mg (600 mg casirivimab and 600 mg imdevimab), which is half the dose initially authorized. As part of the updated EUA, REGEN-COV should be administered by intravenous infusion; subcutaneous injections are an alternative when IV infusion is not feasible and would delay treatment. REGEN-COV has not been approved by FDA but has been Authorized for emergency use.

June 3, 2021 - The U.S. FDA issued a letter that stated: 'having concluded that revising this EUA is appropriate to protect the public health or safety under section 564(g)(2) of the Act, FDA is reissuing the February 25, 2021 letter in its entirety, authorizing revisions to the authorized use6 for REGEN-COV, a change in dosing of REGEN-COV from 2400 mg (1200 mg casirivimab and 1200 mg imdevimab) to 1200 mg (600 mg casirivimab and 600 mg imdevimab), and the addition of a new presentation consisting of a single vial containing casirivimab and imdevimab co-formulated in a 1:1 ratio for either intravenous infusion or subcutaneous injection. New conditions have been incorporated on providing samples of the authorized REGEN-COV to the U.S. Department of Health and Human Services upon request and the submission of certain genomic sequencing and virology information to the FDA by a specified date.'

November 21, 2020 - The U.S. Food and Drug Administration issued an emergency use authorization (EUA) for casirivimab and imdevimab to be administered together for the treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age or older weighing at least 40 kilograms with positive results of direct SARS-CoV-2 viral testing and who are at high risk for progressing to severe COVID-19. This includes 65 years of age or older or certain chronic medical conditions.

June 11, 2020 - Regeneron announced the first clinical trial of REGN-COV2, an investigational antibody cocktail to prevent and treat COVID-19.

REGEN-COV2 (Ronapreve) Monoclonal Antibody Cocktail (Casirivimab and Imdevimab) Clinical Trials

REGEN-COV continues to be studied in various clinical trials to assess safety, Tolerance, Pharmacokinetics, and Immunogenicity against COVID-19.

Phase 3 study - NCT04452318 - Randomized, Double-Blind, Placebo-Controlled Study Assessing the Efficacy and Safety of Anti-Spike SARS-CoV-2 Monoclonal Antibodies in Preventing SARS-CoV-2 Infection in Household Contacts of Individuals Infected With SARS-CoV-2 - published results in the NEJM on September 23, 2021. And on January 14, 2022, the JAMA Network - Conclusions and Relevance:  Among asymptomatic SARS-CoV-2 RT-qPCR–positive individuals living with an infected household contact, treatment with subcutaneous casirivimab and imdevimab antibody combination vs placebo significantly reduced the incidence of symptomatic COVID-19 over 28 days.

Clinical Trials

No clinical trials found