Sarclisa Approved in the US as the First Anti-CD38 Therapy in Combination with Standard-of-Care Treatment for Adult Patients with Newly Diagnosed Multiple Myeloma Not Eligible for Transplant

Brian Foard
Executive Vice President, Head of Specialty Care, Sanofi
“Since first launching in 2020, we have made significant progress towards our ambition of establishing Sarclisa as a best-in-class therapy. The FDA’s decision marks another momentous milestone toward our goal and expands the reach of this potentially transformative therapy to a larger population. With today’s approval, doctors now have an important new option at their disposal that’s been shown to slow disease progression for longer compared to the current standard-of-care for adults living with newly diagnosed multiple myeloma who are not eligible for transplant in the US.”

Results from the IMROZ phase 3 study supporting Sarclisa in NDMM not eligible for ASCT
The FDA approval is based on data from the IMROZ phase 3 study recently presented at the American Society of Clinical Oncology (ASCO) 2024 annual meeting and published in The New England Journal of Medicine. IMROZ is the first global phase 3 study of an anti-CD38 monoclonal antibody in combination with standard-of-care VRd to significantly improve PFS versus VRd alone.

In the IMROZ study, Sarclisa-VRd followed by Sarclisa-Rd met the primary endpoint of PFS, significantly reducing the risk of recurrence or death by 40%, compared to VRd followed by Rd, in patients with NDMM not eligible for ASCT (HR 0.60; 95% CI: 0.44 to 0.81, p=0.0009). At a median follow-up of 59.7 months, the median PFS with the Sarclisa-VRd combination was not reached versus 54.3 months with VRd. The estimated PFS-rate at 60 months was 63.2% for patients treated with Sarclisa-VRd versus 45.2% for VRd.

Sarclisa-VRd also met several secondary endpoints which demonstrated deep responses in this patient population:

• Approximately three-quarters (74.7%) of patients treated with Sarclisa-VRd achieved a complete response (CR) or better compared to 64.1% of patients taking VRd (OR 1.7; 95% CI: 1.097-2.5; p=0.0160).
• More than half (55%) of patients treated with Sarclisa-VRd achieved MRD negative CR compared to 40.9% of patients taking VRd (OR 1.8; 95% CI: 1.229-2.646; p=0.0026).

The safety and tolerability of Sarclisa observed in this study was consistent with the established safety profile of Sarclisa and VRd with no new safety signals observed. The most common adverse reactions (≥20%) were upper respiratory tract infections, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral edema, rash, infusion-related reaction, insomnia, and COVID-19. The most common hematologic laboratory abnormalities (≥80%) were decreased hemoglobin, decreased leukocytes, decreased lymphocytes, decreased platelets, and decreased neutrophils. Serious adverse reactions occurred in 71% of patients receiving Sarclisa combination therapy. The most frequent serious adverse reaction occurring in more than 5% of patients was pneumonia (30%). Permanent discontinuation of treatment due to an adverse reaction occurred in 22.8% of patients treated with Sarclisa combination therapy, compared to 26% in the comparator arm.

Advancing Sarclisa in multiple myeloma
Sanofi continues to advance Sarclisa as part of a patient-centric clinical development program, which includes several phase 2 and phase 3 studies across the MM treatment continuum spanning six potential indications. In addition, the company is evaluating a subcutaneous administration method for Sarclisa in clinical studies. The safety and efficacy of Sarclisa has not been evaluated by any regulatory authority outside of its approved indications and methods of delivery.

In September, isatuximab-irfc (Sarclisa) was also added to the National Comprehensive Cancer Network (NCCN^®) Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for MM non-transplant candidates as an NCCN Category 1 Preferred option in combination with VRd for patients

*NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

About Sarclisa
Sarclisa (isatuximab-irfc) is a monoclonal antibody that binds to a specific epitope on the CD38 receptor on MM cells, inducing distinct antitumor activity. 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 target for antibody-based therapeutics such as Sarclisa.

Based on the ICARIA-MM phase 3 study, Sarclisa is approved in more than 50 countries, including the US and the EU, in combination with pomalidomide and dexamethasone for the treatment of patients with relapsed refractory MM (RRMM) who have received ≥2 prior therapies, including lenalidomide and a proteasome inhibitor and who progressed on last therapy. Based on the IKEMA phase 3 study. Sarclisa is also approved in 50 countries in combination with carfilzomib and dexamethasone, including in the US for the treatment of patients with RRMM who have received 1–3 prior lines of therapy and in the EU for patients with MM who have received at least one prior therapy. In the US, the non-proprietary name for Sarclisa is isatuximab-irfc, with irfc as the suffix designated in accordance with nonproprietary naming of biological products guidance for industry issued by the US Food and Drug Administration.

Sarclisa continues to be evaluated in multiple ongoing phase 3 clinical studies in combination with current standard treatments across the MM treatment continuum. It is also under investigation for the treatment of other hematologic malignancies, and its safety and efficacy have not been evaluated by any regulatory authority outside of its approved indication.

Sanofi is committed to pursuing the advancement of Sarclisa through several investigational studies across the MM treatment continuum. Various patient-centric clinical development programs aim to bring Sarclisa to more patients, intercept the disease earlier in the treatment journey, explore potential new combinations and assess subcutaneous administration via a proprietary on body device system. The safety and efficacy of Sarclisa has not been evaluated by any regulatory authority outside of its approved indications and methods of delivery.

In striving to become the number one immunoscience company globally, Sanofi remains committed to advancing oncology innovation. Through focused strategic decisions the company has reshaped and prioritized its pipeline, leveraging its expertise in immunoscience to drive progress. Efforts are centered on difficult-to-treat cancers such as select hematologic malignancies, and solid tumors with critical unmet needs, including multiple myeloma, acute myeloid leukemia, certain types of lymphomas, as well as gastrointestinal and lung cancers.

For more information on Sarclisa clinical studies, please visit www.clinicaltrials.gov.

About multiple myeloma
MM is the second most common hematologic malignancy¹, affecting more than 130,000 patients in the US; approximately 32,000 Americans are diagnosed with MM each year.² Despite available treatments, MM remains an incurable malignancy with an estimated 52% five-year survival rate for newly diagnosed patients.³ According to physician-based surveys, the majority of NDMM patients are not considered eligible for transplant, creating a need for new frontline therapeutic options, particularly due to high attrition rates in subsequent lines of therapy.

IMPORTANT SAFETY INFORMATION AND INDICATION FOR US 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.
• The medicines bortezomib, lenalidomide and dexamethasone, to treat adults with newly diagnosed multiple myeloma who cannot receive a type of stem cell transplant that uses their own stem cells (autologous stem cell transplant).

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

Important Safety Information

Do not receive Sarclisa if you have 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 an infection.
• Have heart problems, if your healthcare provider prescribes Sarclisa in combination with carfilzomib and dexamethasone for you.
• Have had shingles (herpes zoster).
• Are pregnant or plan to become pregnant. Sarclisa can harm your unborn baby.

  • 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.
  • Before receiving Sarclisa in combination with either pomalidomide or lenalidomide, females and males must agree to the instructions in the pomalidomide or lenalidomide REMS program. The pomalidomide and lenalidomide REMS program have specific requirements about birth control, pregnancy testing, blood donation, and sperm donation that you need to know. Talk to your healthcare provider to learn more about pomalidomide or lenalidomide.

• 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, vitamins, and herbal supplements.

How will I receive Sarclisa?

• Sarclisa will be given to you by your healthcare provider by intravenous (IV) infusion into your vein.
• Sarclisa in combination with pomalidomide and dexamethasone, or Sarclisa in combination with carfilzomib and dexamethasone is given in treatment cycles of 28 days (4 weeks).

  • Cycle 1 (28-day cycle), Sarclisa is given weekly.
  • Cycle 2 and beyond (28-day cycles), Sarclisa is given every 2 weeks.

• Sarclisa in combination with bortezomib, lenalidomide, and dexamethasone is given in treatment cycles of 42 days (6 weeks) from cycle 1 to 4 and in treatment cycles of 28 days (4 weeks) from cycle 5.

  • Cycle 1 (42-day cycle), Sarclisa is given weekly (Days 1, 8, 15, 22, and 29).
  • Cycles 2 to 4 (42-day cycles), Sarclisa is given every 2 weeks (Days 1, 15, and 29).
  • Cycles 5 to 17 (28-day cycles), Sarclisa is given every 2 weeks (Days 1 and 15).
  • Cycles 18 and beyond (28-day cycles), Sarclisa is given every 4 weeks.

• Your healthcare provider will decide how many treatments you will receive.
• Your healthcare provider will give you medicines before each infusion of Sarclisa to help reduce the risk of infusion reactions (make them less frequent and severe).
• If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.

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

• Infections. Sarclisa can cause infections that are severe, life-threatening, or that may lead to death. Your healthcare provider will monitor you for signs and symptoms of infection before and during treatment with Sarclisa. Your healthcare provider may prescribe medicines for you to help prevent infections and treat you as needed if you develop an infection during treatment with Sarclisa. Tell your healthcare provider right away if you develop a fever or any signs or symptoms of infection during treatment with Sarclisa.
• Decreased white blood cell counts. Decreased white blood cell counts are common with Sarclisa and certain white blood cells can be severely decreased. Fever can occur with low white blood cell counts and may be a sign that you have an infection. Your healthcare provider will check your blood cell counts during treatment with Sarclisa and may prescribe a medicine to help increase your white blood cell counts. 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 and after 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.

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

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

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

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

The most common side effects of Sarclisa in combination with bortezomib, lenalidomide and dexamethasone include:

• upper respiratory tract infection
• constipation
• diarrhea
• swelling of the hands, legs, ankles and feet
• tiredness and weakness
• rash
• tingling or numbness of the arms or legs
• trouble sleeping
• lung infection (pneumonia)
• COVID-19
• muscle or bone pain
• decreased red blood cell count (anemia)
• clouding of your eye (cataract)
• decreased platelet count (thrombocytopenia)

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