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The Phase 3 HD7 trial, conducted by the German-Speaking Myeloma Multicenter Group (GMMG), met the primary endpoint, the rate of minimal residual disease (MRD) negativity after induction therapy and before transplant in patients with newly diagnosed multiple myeloma (MM) treated with Sarclisa^® (isatuximab) in combination with lenalidomide, bortezomib and dexamethasone (RVd). This is the first Phase 3 trial to evaluate MRD negativity at the end of induction as a primary endpoint, and to demonstrate statistically significant improvement in rates of MRD negativity in this patient population by adding an anti-CD38 monoclonal antibody to RVd. MRD negativity is an important clinical endpoint associated with better patient outcomes, which is meaningful for MM where most patients relapse.[i]

“It is unprecedented for half of patients to achieve MRD negativity this early in treatment with this regimen,” said Hartmut Goldschmidt, M.D., President of GMMG, Professor of Medicine at the Heidelberg University Hospital (UKHD), Germany and principal investigator of the study. “We know that achieving deeper responses earlier in treatment may translate to longer periods of progression free survival and are excited about these results.”

After an induction phase of 18 weeks, the rate of MRD negativity for patients receiving Sarclisa combination therapy (n=331) was 50.1% versus 35.6% for those who received RVd (n=329) (odds ratio [OR]=1.83; 95% confidence interval [CI]: 1.34-2.51; p<0.001). The safety and tolerability of Sarclisa observed in this trial was consistent with the observed safety profile of Sarclisa in other clinical trials, with no new safety signals observed. Rates of all adverse events observed were 63.6% for the Sarclisa combination versus 61.3% for RVd and serious adverse effects and discontinuations were similar in both study arms (34.8% versus 36.3%, respectively). However, the number of deaths were higher in the RVd arm (1.2% versus 2.4%) during the induction period. The trial is ongoing, following the second randomization to evaluate progression free survival (PFS) for Sarclisa and lenalidomide combination as maintenance therapy.

“The results of this trial reinforce our belief in Sarclisa’s potential to become the anti-CD38 of choice,” said Peter C. Adamson, Global Development Head, Oncology at Sanofi. “To observe such a high proportion of patients who have MRD negative disease following a relatively brief induction period is highly encouraging. We look forward to our continued collaborative efforts with GMMG to deliver a potential treatment option to transplant-eligible patients with newly diagnosed multiple myeloma.”

MRD negativity is defined as the absence of myeloma cells in the bone marrow after treatment, as measured by diagnostic techniques that must have a sensitivity of at least 1 in 100,000 cells.[ii] This assessment is the most sensitive tool to measure the depth of response to treatment in patients with MM.[iii]

This GMMG initiated clinical trial was conducted in close collaboration with Sanofi based on jointly defined research. Sanofi provided financial support to GMMG for this study.

The use of Sarclisa in combination with RVd is investigational and has not been evaluated by any regulatory authority.

About the trial
The pivotal, randomized, open-label, multicenter, Phase 3 GMMG-HD7 trial is a two-part study that enrolled 662 patients with newly diagnosed, transplant-eligible MM across 67 sites in Germany. In the first part of the study, all participants were equally randomized to receive three 42-day cycles of RVd in both arms of the trial, while Sarclisa was added to only one trial arm. During the trial, Sarclisa was administered through an intravenous infusion at a dose of 10 mg/kg once weekly for the first four weeks of cycle one, then every other week for the rest of the induction period.

MRD negativity was assessed by next-generation flow cytometry (cut off 1x10^-5) after induction. An odds ratio was used to measure this endpoint to determine the association between adding Sarclisa to standard of care and participants achieving MRD negativity.

The primary endpoints are MRD negativity after induction treatment for the first part of the study, and PFS following the second randomization after transplant for part two of the study, in which Sarclisa is added to lenalidomide maintenance. Secondary endpoints include rates of complete response after induction, overall survival after maintenance therapy and safety.

About Sarclisa
Sarclisa is a monoclonal antibody that targets 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.

Based on the Phase 3 ICARIA-MM study, Sarclisa is approved in a number of countries 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. Based on the Phase 3 IKEMA study, Sarclisa is also approved in combination with carfilzomib and dexamethasone in the U.S. for the treatment of patients with RRMM who have received 1–3 prior lines of therapy and in the European Union for patients with MM who have received at least 1 prior therapy. In the U.S., the generic 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 U.S. Food and Drug Administration (FDA).

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

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

About multiple myeloma
MM is the second most common hematologic malignancy,[iv] with more than 130,000 new diagnoses of MM worldwide yearly.[v] 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 the German-Speaking Myeloma Multicenter Group (GMMG)
GMMG is the largest study group focusing on MM in Germany, with headquarters based in Heidelberg. Within the last 20 years, the GMMG study group has performed numerous trials including five randomized, multicenter Phase 3 clinical trials with 4,000 patients enrolled from about 90 participating and co-treating centers throughout Germany. The overall goal of GMMG is to generate improved therapies for myeloma patients through the development and testing of novel and personalized, genome- and signaling-driven treatment strategies.

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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