The Second Phase III Trial Of Sanclifi CD38 Antibody Sarclisa Succeeded Ahead Of Schedule, Challenging Johnson And Johnson's $ 3 Billion Blockbuster Darzalex

- May 24, 2020-

Sanofi (Sanofi) recently announced that it has achieved positive results in a phase III IKEMA clinical trial evaluating the CD38 targeting antibody drug Sarclisa (isatuximab) for relapsed and / or refractory multiple myeloma (MM).


IKEMA (NCT03275285) is a randomized, multicenter, open-label phase III clinical trial enrolling 302 patients with relapsed and / or refractory multiple myeloma (MM) in 69 clinical centers in 16 countries. This patient had previously received 1-3 anti-myeloma therapies. During the trial, Sarclisa was infused intravenously at a dose of 10 mg / kg, once a week for four weeks, and then infused once every other week. Carfilzomib was dosed at 20/56 mg / m2 twice a week. The standard dose was used during treatment Dexamethasone. The primary endpoint of the IKEMA trial is progression-free survival (PFS). Secondary endpoints include overall response rate (ORR), good partial response or better response (≥VGPR), minimal residual disease (MRD), complete response rate (CR), overall survival (OS), and safety.


The results showed that in the first pre-planned mid-term analysis, the trial had reached its primary endpoint. According to the recommendations of the Independent Data Monitoring Committee (IDMC), the trial results are announced in advance: compared with the standard care regimen carfilzomib (Kyprolis®) + dexamethasone, Sarclisa + carfilzomib + dexamethasone three drugs The protocol significantly prolonged progression-free survival (PFS), significantly reduced the risk of disease progression or death, and no new safety signals were found in the trial.


The results of the trial will be announced at an upcoming medical conference and will serve as the basis for filing regulatory applications later this year. John Reed, MD, Sanofi ’s global head of research and development, said: “In this phase III clinical trial, Sarclisa was added to carfilzomib and dexamethasone standard care regimens, and the results clearly indicated a significant risk of disease progression or death Reduced. This is Sarclisa ’s second positive phase III trial and further supports the potential of our drug to improve the prognosis of patients with relapsed multiple myeloma. "

Sarclisa-isatuximab

Multiple myeloma (MM) is the second most common blood cancer, with more than 138,000 newly diagnosed cases worldwide each year. In Europe, 39,000 cases are diagnosed each year; in the United States, 32,000 cases are diagnosed each year. Despite the available treatments, MM is still an incurable malignant tumor and is associated with a severe burden on patients. Because MM cannot be cured, most patients will eventually relapse and no longer respond to the currently available therapies.


Sarclisa's active pharmaceutical ingredient isatuximab is an IgG1 chimeric monoclonal antibody that targets specific epitopes on the CD38 receptor of plasma cells and can trigger a variety of unique mechanisms of action, including the promotion of programmed tumor cell death (apoptosis) and immunity Regulate activity. CD38 is expressed at high levels on multiple myeloma (MM) cells and is a cell surface receptor target for antibody therapy in MM and other malignant tumors. In the United States and the European Union, isatuximab has been granted orphan drug status for the treatment of relapsed or refractory multiple myeloma (R / R MM). Currently, Sanofi is also evaluating the potential of isatuximab in the treatment of other hematological malignancies and solid tumors.


In March this year, Sarclisa was approved by the US FDA to combine pomalidomide and dexamethasone (pom-dex) for RRMM adults who have previously received at least 2 therapies (including lenalidomide and proteasome inhibitors) patient. At the end of March this year, Sarclisa's joint pom-dex program also received positive comments from the European Medicines Agency (EMA) Committee on Human Pharmaceutical Products (CHMP) for approval. The European Commission (EC) is expected to make a final review decision in May.


Sarclisa received regulatory approval based on data from the key Phase III ICARIA-MM study. This is the first phase III study to evaluate the positive results of Sarclisa combined with standard care programs, and it enrolls patients with relapsed and refractory multiple myeloma that are particularly difficult to treat and have a poor prognosis (median of anti-myeloma therapy received 3 types), reflecting the real world clinical practice. The results showed that in these patients, the combined treatment of Sarclisa and pom-dex significantly prolonged the progression-free survival of the disease compared to standard care (pomidol + dexamethasone, pom-dex) (median PFS: 11.53 Months vs 6.47 months), the risk of disease progression or death was significantly reduced by 40% (HR = 0.596; 95% CI: 0.44-0.81; p = 0.0010), and the overall response rate was significantly improved (ORR: 60.4% vs 35.3%, p <0.0001), and showed therapeutic benefits in various subgroups, including patients ≥75 years of age, patients with renal insufficiency, and refractory patients with lenalidomide.


Sarclisa will become the first direct competitor of Johnson & Johnson's heavyweight CD38 targeted drug Darzalex after its launch. The latter was launched in 2015, with global sales reaching US $ 2.998 billion in 2019, an increase of 48.0% from the previous year. Wall Street Investment Bank Jefferies analysts expect Sarclisa ’s annual sales peak to exceed $ 1 billion after its listing.


Currently, Sanofi is advancing multiple phase III clinical studies to evaluate isatuximab in combination with currently available standard therapies for the treatment of RRMM patients or newly diagnosed MM patients. MM is the second most common malignant tumor of the blood system, with more than 1.38 million patients worldwide each year. For most patients, MM is still incurable, so there is a significant unmet medical need in this area.