Regeneron and Sanofi Provide Update on Kevzara® (sarilumab) Phase 3 U.S. Trial in COVID-19 Patients

Regeneron Pharmaceuticals, Inc. issued the following announcement on July 2.

Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced that the U.S. Phase 3 trial of Kevzara® (sarilumab) 400 mg in COVID-19 patients requiring mechanical ventilation did not meet its primary and key secondary endpoints when Kevzara was added to best supportive care compared to best supportive care alone (placebo).

Minor positive trends were observed in the primary pre-specified analysis group (critical patients on Kevzara 400 mg who were mechanically ventilated at baseline) that did not reach statistical significance, and these were countered by negative trends in a subgroup of critical patients who were not mechanically ventilated at baseline.1 In the primary analysis group, adverse events were experienced by 80% of Kevzara patients and 77% of placebo patients.  Serious adverse events that occurred in at least 3% of patients and more frequently among Kevzara patients were multi-organ dysfunction syndrome (6% Kevzara, 5% placebo) and hypotension (4% Kevzara, 3% placebo).

Based on the results, the U.S.-based trial has been stopped, including in a second cohort of patients who received a higher dose of Kevzara (800 mg). Detailed results will be submitted to a peer-reviewed publication later this year. 

The primary analysis group included 194 patients who were critically ill with COVID-19 and were receiving mechanical ventilation at the time of enrollment. The primary endpoint assessed the percentage of patients who achieved at least a 1-point change from baseline on a 7-point scale, which consisted of 1) death; 2) hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) hospitalized, requiring non-invasive ventilation or high-flow oxygen devices; 4) hospitalized, requiring supplemental oxygen; 5) hospitalized, not requiring supplemental oxygen – requiring ongoing medical care (COVID-19 related or otherwise); 6) hospitalized, not requiring supplemental oxygen – no longer requires ongoing medical care; 7) discharged from hospital. A second cohort, which was partially recruited (n=27), compared Kevzara 800 mg versus placebo.

The Kevzara trial was designed after a small (n=21), single-arm study in China (Xu et al) among mostly severe, febrile, hospitalized COVID-19 patients found elevated IL-6 levels and suggested that inhibiting this pathway with the IL-6 blocker tocilizumab rapidly reduced fever and improved oxygenation in severe patients, allowing for successful hospital discharge. The Phase 3 Kevzara trial was designed to evaluate this hypothesis in a large, placebo-controlled trial. The trial has been funded in part with federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; and Biomedical Advanced Research and Development Authority (BARDA), under OT number: HHSO100201700020C.

A separate Sanofi-led trial outside of the U.S. in hospitalized patients with severe and critical COVID-19 using a different dosing regimen is ongoing. The same Independent Data Monitoring Committee (IDMC) is overseeing both the Regeneron-led U.S. trial and the Sanofi-led trial outside of U.S. and has recommended that the trial outside of the U.S. continue. The companies expect to report results of the trial outside of the U.S. in Q3 2020.

Footnote

1. Clinical trial endpoints that showed positive trends in patients on mechanical ventilation at baseline, and were countered by negative trends in patients who were not mechanically ventilated at baseline included: the proportion of patients with a 1-point improvement on day 22 (primary endpoint for mechanical ventilation group); the proportion of patients who died by day 29; and the proportion of patients who recovered by day 22.

About Kevzara® (sarilumab) Injection

Kevzara is currently approved in multiple countries to treat adults with moderately to severely active rheumatoid arthritis who have not responded to or tolerated previous therapy.

Kevzara binds specifically to the IL-6 receptor, and has been shown to inhibit IL-6-mediated signaling. IL-6 is an immune system protein produced in increased quantities in patients with rheumatoid arthritis and has been associated with disease activity, joint destruction and other systemic problems. Kevzara is being investigated for its ability to reduce the overactive inflammatory immune response associated with COVID-19 based on evidence of markedly elevated levels of IL-6 in critically ill patients infected with coronaviruses.

IMPORTANT SAFETY INFORMATION FOR KEVZARA® (sarilumab) INJECTION

KEVZARA can cause serious side effects including:

• SERIOUS INFECTIONS: KEVZARA is a medicine that affects your immune system. KEVZARA can lower the ability of your immune system to fight infections. Some people have serious infections while using KEVZARA, including tuberculosis (TB), and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have died from these infections. Your healthcare provider should test you for TB before starting KEVZARA. Your healthcare provider should monitor you closely for signs and symptoms of TB during treatment with KEVZARA.
  • Before starting KEVZARA, tell your healthcare provider if you:
    • think you have an infection or have symptoms of an infection, with or without a fever. Symptoms may include sweats or chills, muscle aches, a cough, shortness of breath, blood in your phlegm, weight loss, warm, red, or painful skin or sores on your body, diarrhea or stomach pain, burning when you urinate or urinating more often than normal, if you feel very tired, or if you are being treated for an infection, get a lot of infections or have repeated infections
    • have diabetes, HIV, or a weakened immune system
    • have TB, or have been in close contact with someone with TB
    • live or have lived, or have traveled to certain parts of the country (such as the Ohio and Mississippi River valleys and the Southwest) where there is an increased chance of getting certain fungal infections (histoplasmosis, coccidioidomycosis, or blastomycosis)
    • have or have had hepatitis
    • After starting KEVZARA, call your healthcare provider right away if you have any symptoms of an infection.
• CHANGES IN CERTAIN LABORATORY TEST RESULTS: Your healthcare provider should do blood tests before and after starting KEVZARA to check for low neutrophil (white blood cells that help the body fight off bacterial infections) counts, low platelet (blood cells that help with blood clotting and stop bleeding) counts, and an increase in certain liver function tests. Changes in test results are common with KEVZARA and can be severe.  You may also have changes in other laboratory tests, such as your blood cholesterol levels. Your healthcare provider should do blood tests 4 to 8 weeks after starting KEVZARA and then every 6 months during treatment to check for an increase in blood cholesterol levels.
  • TEARS (PERFORATION) OF THE STOMACH OR INTESTINES: Tell your healthcare provider if you have had a condition known as diverticulitis (inflammation in parts of the large intestine) or ulcers in your stomach or intestines. Some people using KEVZARA had tears in their stomach or intestine. This happens most often in people who also take nonsteroidal anti-inflammatory drugs (NSAIDS), corticosteroids, or methotrexate. Call your healthcare provider right away if you have fever and stomach (abdominal) pain that does not go away.
  • CANCER: KEVZARA may increase your risk of certain cancers by changing the way your immune system works.  Tell your healthcare provider if you have ever had any type of cancer.
  • SERIOUS ALLERGIC REACTIONS: Serious allergic reactions can happen with KEVZARA.  Get medical attention right away if you have any of the following signs: shortness of breath or trouble breathing; feeling dizzy or faint; swelling of your lips, tongue or face; moderate or severe stomach (abdominal) pain or vomiting; or chest pain.
  • Do not use KEVZARA if you are allergic to Sarilumab or any of the ingredients of KEVZARA.
  • Before using KEVZARA, tell your healthcare provider if you
    • have an infection
    • have liver problems
    • have had stomach (abdominal) pain or a condition known as diverticulitis (inflammation in parts of the large intestine) or ulcers in your stomach or intestines
    • recently received or are scheduled to receive a vaccine. People who take KEVZARA should not receive live vaccines 
    • plan to have surgery or a medical procedure
    • are pregnant or plan to become pregnant. It is not known if KEVZARA will harm your unborn baby
    • are breastfeeding or plan to breastfeed. Talk to your healthcare provider about the best way to feed your baby if you use KEVZARA.  It is not known if KEVZARA passes into your breast milk
    • take any prescription or nonprescription medicines, vitamins or herbal supplements. It is especially important to tell your healthcare provider if you use any other medicines to treat your RA.   Using KEVZARA with these medicines may increase your risk of infection
    • medicines that affect the way certain liver enzymes work. Ask your healthcare provider if you are not sure if your medicine is one of these
• The most common side effects include:
  • injection site redness
  • upper respiratory tract infection
  • urinary tract infection
  • nasal congestion, sore throat, and runny nose

These are not all the possible side effects of KEVZARA. Tell your doctor about any side effect that bothers you or does not go away. You are encouraged to report side effects of prescription drugs to the FDA at www.fda.gov/medwatch or call 1-800-FDA-1088.

WHAT IS KEVZARA?

Kevzara is an injectable prescription medicine called an interleukin-6 (IL-6) receptor blocker. Kevzara is used to treat adult patients with moderately to severely active rheumatoid arthritis (RA) after at least one other medicine called a disease-modifying antirheumatic drug (DMARD) has been used and did not work well or could not be tolerated.

Click here for full Prescribing Information including risk of SERIOUS SIDE EFFECTS and Medication Guide for KEVZARA.

About Regeneron Pharmaceuticals, Inc.

Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents life-transforming medicines for people with serious diseases. Founded and led for over 30 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to seven FDA-approved treatments and numerous product candidates in development, all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, pain, infectious diseases and rare diseases.

Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune which uses unique genetically-humanized mice to produce optimized fully-human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center, which is conducting one of the largest genetics sequencing efforts in the world.

For additional information about the company, please visit www.regeneron.com or follow @Regeneron on Twitter.

About Sanofi

Sanofi is dedicated to supporting people through their health challenges. We are a global biopharmaceutical company focused on human health. We prevent illness with vaccines, provide innovative treatments to fight pain and ease suffering. We stand by the few who suffer from rare diseases and the millions with long-term chronic conditions.

With more than 100,000 people in 100 countries, Sanofi is transforming scientific innovation into healthcare solutions around the globe.

Sanofi, Empowering Life

Original source can be found here.