FDA approves Sarclisa(R) (isatuximab-irfc) in combination with carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma

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PARIS, March 31, 2021 -- The U.S. Food and Drug Administration (FDA) has approved Sarclisa(R) (isatuximab-irfc) in combination with carfilzomib and dexamethasone (Kd), for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received one to three prior lines of therapy.

"In the Phase 3 IKEMA study, the addition of Sarclisa to carfilzomib and dexamethasone reduced risk of disease progression or death by 45%," said Thomas G. Martin, M.D., Associate Director, Myeloma Program, The University of California, San Francisco, Professor of Medicine, Adult Leukemia and Bone Marrow Transplantation Program and co-leader of the Hematopoietic Malignancies Program, Helen Diller Family Comprehensive Cancer Center. "This approval is an important advancement for patients whose disease has relapsed and reinforces the potential for Sarclisa to become a standard of care in relapsed or refractory multiple myeloma."

This marks the second FDA approval for Sarclisa, which is also approved in combination with pomalidomide and dexamethasone (pom-dex) for the treatment of adults with RRMM who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.

"Treatment of patients with relapsed or refractory multiple myeloma remains challenging and the prognosis for patients experiencing multiple relapses unfortunately is poor," said Peter C. Adamson, M.D., Global Development Head, Oncology and Pediatric Innovation at Sanofi. "With this approval, Sarclisa is now included in two standard of care regimens for the treatment of patients with multiple myeloma as early as first relapse. Today's milestone further supports our ambition for Sarclisa to become the anti-CD38 of choice for patients with relapsed or refractory multiple myeloma."

Sarclisa Phase 3 IKEMA pivotal trial results supporting approval

The FDA approval is based on data from the Phase 3 IKEMA study, a randomized, multi-center, open label clinical trial that enrolled 302 patients with relapsed multiple myeloma across 69 centers spanning 16 countries.1 In this study, Sarclisa added to Kd (Sarclisa combination therapy) reduced the risk of disease progression or death by 45% (hazard ratio 0.548, 95% CI 0.366-0.822, p=0.0032) versus standard of care Kd alone in patients with multiple myeloma. The median progression free survival (PFS) for Sarclisa combination therapy was not reached at the time of the pre-planned interim analysis. This study enrolled a difficult-to-treat patient population, including those who are elderly, have high cytogenetic risk or renal impairment. Overall, demographic and disease characteristics at baseline were balanced between the two treatment groups.2

Secondary endpoints of the IKEMA trial assessed the overall response rate (ORR) for Sarclisa combination therapy compared to Kd, including complete response (CR) and very good partial response (VGPR). There was no statistically significant difference in ORR, which remained similar for each arm at 86.6% for the Sarclisa combination therapy versus 82.9% for Kd (p=0.3859). The rate of CR was 39.7% in the Sarclisa combination therapy arm and 27.6% in the Kd arm. The rate of VGPR was 33% for patients receiving Sarclisa combination therapy and 28.5% for patients receiving Kd.2 At the time of the interim analysis, overall survival (OS) data were still immature.3

The most frequent adverse reactions (occurring in 20% or more of patients) for Sarclisa versus the control arm were upper respiratory tract infection (67% vs. 57%), infusion-related reactions (46% vs. 3.3%), fatigue (42% vs. 32%), hypertension (37% vs. 32%), diarrhea (36% vs. 29%), pneumonia (36% vs. 30%), dyspnea (29% vs. 24%), bronchitis (24% vs. 13%), and cough (23% vs. 15%). Serious adverse reactions that occurred in more than 5% of patients who received Sarclisa combination therapy were pneumonia (25%) and upper respiratory tract infections (9%). Permanent discontinuation of treatment because of adverse reactions (Grade 1-4) occurred in 8% of patients treated with Sarclisa combination therapy, and 2.8% of patients discontinued due to an infection.2

Multiple Myeloma: an incurable blood cancer, with significant burden

Multiple Myeloma (MM) is the second most common hematologic malignancy4, affecting more than 130,000 patients in the United States; approximately 32,000 Americans are diagnosed with multiple myeloma each year.5 Despite available treatments, MM remains an incurable malignancy, and is associated with significant patient burden. Since MM does not have a cure, most patients will relapse. Relapsed MM is the term for when the cancer returns after treatment or a period of remission. Refractory MM refers to when the cancer does not respond or no longer responds to therapy.

About Sarclisa

Sarclisa is a monoclonal antibody that binds to a specific epitope on the CD38 receptor on MM cells. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on the surface of MM cells, making it a potential target for antibody-based therapeutics such as Sarclisa.

This marks the second FDA approval for Sarclisa since March 2020 and comes more than three months ahead of the FDA's target action date. In February, the European Medicines Agency's Committee for Medicinal Products for Human Use adopted a positive opinion for a second indication for Sarclisa, in combination with carfilzomib and dexamethasone (Kd), for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. The use of Sarclisa in combination with Kd is not currently approved in the European Union (EU), but the final decision whether to expand the indication is expected from the European Commission in the coming months. In Europe, Sarclisa is indicated in combination with pom-dex for the treatment of adult patients with RRMM who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on the last therapy. Outside of the U.S. and the EU, Sarclisa is approved in Switzerland, Canada, Australia, Japan, Russia, the UAE, South Korea, Taiwan and Brazil in combination with pom-dex for the treatment of certain adults with RRMM.

Sarclisa continues to be evaluated in multiple ongoing Phase 3 clinical trials in combination with current standard and novel treatments across the MM treatment continuum. It is also under investigation for the treatment of other hematologic malignancies and solid tumors. The use of Sarclisa in these additional settings is currently under clinical investigation and its safety and efficacy have not been fully evaluated by any regulatory authority.

IMPORTANT SAFETY INFORMATION AND INDICATION FOR U.S. PATIENTS

What is SARCLISA?

SARCLISA is a prescription medicine used in combination with:

  • The medicines pomalidomide and dexamethasone, to treat adults who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor to treat multiple myeloma.
  • The medicines carfilzomib and dexamethasone, to treat adults with multiple myeloma who have already received 1 to 3 lines of treatment and they did not work or are no longer working.

It is not known if SARCLISA is safe and effective in children.

Important Safety Information

Do not receive SARCLISA if you have a history of a severe allergic reaction to isatuximab-irfc or any of the ingredients in SARCLISA (see the list of ingredients in the full Prescribing Information).

Before receiving SARCLISA, tell your healthcare provider about all of your medical conditions, including if you:

  • Have heart problems, if your healthcare provider prescribes SARCLISA in combination with carfilzomib and dexamethasone for you.
  • Are pregnant or plan to become pregnant. SARCLISA may harm your unborn baby. You should not receive SARCLISA during pregnancy.
    • Females who are able to become pregnant should use an effective method of birth control during treatment and for 5 months after your last dose of SARCLISA. Talk to your healthcare provider about birth control methods that you can use during this time.
      Tell your healthcare provider right away if you think you are pregnant or become pregnant during treatment with SARCLISA.
  • Are breastfeeding or plan to breastfeed. It is not known if SARCLISA passes into your breast milk. You should not breastfeed during treatment with SARCLISA.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines. Especially tell your healthcare provider if you have ever taken a medicine for your heart.

How will I receive SARCLISA?

  • SARCLISA will be given to you by your healthcare provider by intravenous (IV) infusion into your vein.
  • SARCLISA is given in treatment cycles of 28 days (4 weeks), together with either the medicines pomalidomide and dexamethasone, or carfilzomib and dexamethasone.
    • In cycle 1, SARCLISA is usually given weekly.
    • Starting in cycle 2, SARCLISA is usually given every 2 weeks.
  • If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.
  • Your healthcare provider will give you medicines before each dose of SARCLISA to help reduce the risk of infusion reactions (make them less frequent and severe).

What are the possible side effects of SARCLISA?

SARCLISA may cause serious side effects, including:

  • Infusion reactions. Infusion reactions are common with SARCLISA and can sometimes be severe or life threatening.
    • Your healthcare provider will prescribe medicines before each infusion of SARCLISA to help decrease your risk for infusion reactions or to help make any infusion reaction less severe. You will be monitored for infusion reactions during each dose of SARCLISA.
    • Your healthcare provider may slow down or stop your infusion, or completely stop treatment with SARCLISA if you have an infusion reaction.

Get medical help right away if you develop any of the following symptoms of infusion reaction during or after an infusion of SARCLISA:

-- shortness of breath, wheezing, or trouble breathing
-- swelling of the face, mouth, throat, or tongue
-- throat tightness
-- palpitations
-- dizziness, lightheadedness, or fainting
-- headache
-- cough
-- rash or itching
-- nausea
-- runny or stuffy nose
-- chills

  • Decreased white blood cell counts. Decreased white blood cell counts are common with SARCLISA and certain white blood cells can be severely decreased. You may have an increased risk of getting certain infections, such as upper and lower respiratory tract infections and urinary tract infections.

    Your healthcare provider will check your blood cell counts during treatment with SARCLISA. Your healthcare provider may prescribe an antibiotic or antiviral medicine to help prevent infection, or a medicine to help increase your white blood cell counts during treatment with SARCLISA.

Tell your healthcare provider right away if you develop any fever or symptoms of infection during treatment with SARCLISA.

  • Risk of new cancers. New cancers have happened in people during treatment with SARCLISA. Your healthcare provider will monitor you for new cancers during treatment with SARCLISA.
  • Change in blood tests. SARCLISA can affect the results of blood tests to match your blood type. Your healthcare provider will do blood tests to match your blood type before you start treatment with SARCLISA. Tell all of your healthcare providers that you are being treated with SARCLISA before receiving blood transfusions.
  • Heart failure. Heart failure can happen during treatment with SARCLISA in combination with carfilzomib and dexamethasone. Tell your healthcare provider right away if you develop any of the following symptoms:

- trouble breathing

- cough

- swelling of your ankles, feet, or legs

The most common side effects of SARCLISA in combination with pomalidomide and dexamethasone include:

  • lung infection (pneumonia)
  • decreased red blood cell counts (anemia)
  • upper respiratory tract infection
  • decreased platelet counts (thrombocytopenia)
  • diarrhea

The most common side effects of SARCLISA in combination with carfilzomib and dexamethasone include:

  • upper respiratory tract infection
  • tiredness and weakness
  • high blood pressure
  • diarrhea
  • lung infection (pneumonia)
  • trouble breathing
  • trouble sleeping
  • bronchitis
  • cough
  • back pain
  • decreased red blood cells (anemia)
  • decreased platelet counts (thrombocytopenia)

These are not all the possible side effects of SARCLISA. For more information, ask your healthcare provider or pharmacist.

Please see full Prescribing Information, including Patient Information

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.

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1 Multinational Clinical Study Comparing Isatuximab, Carfilzomib And Dexamethasone To Carfilzomib And Dexamethasone In Relapse And/Or Refractory Multiple Myeloma Patients (IKEMA). NCT03275285. Retrieved from: https://clinicaltrials.gov/ct2/show/NCT03275285
2 Sarclisa Prescribing Information. March 2020.
3 Moreau et. al. Isatuximab Plus Carfilzomib And Dexamethasone Vs Carfilzomib And Dexamethasone In Relapsed/Refractory Multiple Myeloma (Ikema): Interim Analysis Of A Phase 3, Randomized, Open-Label Study. Oral presentation at European Hematology Association Virtual Congress 2020. June 12, 2020
4 Kazandjian. Multiple myeloma epidemiology and survival: A unique malignancy. Semin Oncol. 2016;43(6):676-681. doi:10.1053/j/seminoncol.2016.11.004
5 National Cancer Institute. Myeloma Cancer Stat Facts. Available at: www.seer.cancer.gov/statfacts/html/mulmy.html. Accessed on February 22, 2021.

Source: Sanofi (EURONEXT: SAN) (NASDAQ: SNY)

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