Investigational Drugs for Multiple myeloma

Multiple myeloma is a cancer of plasma cells. While 90% of patients will survive to five years, expectancy decreases with more serious stages. Median survival is 83 months for Stage II patients and drops to 43 months for Stage 3 patients.
 
We are currently tracking four drugs in development for multiple myeloma
 
Opaganib, an oral SK2 inhibitor being developed by RedHill Biopharma and has been designated an orphan drug by the FDA. Redhill announced interim results from the Phase Ib part of a Phase Ib/II refractory or relapsed multiple myeloma trial where 2 patients had stable disease for over four months and one a partial response. Redhill has three ongoing Phase II trials evaluating opaganib for the treatment of cholangiocarcinoma, advanced liver cancer and multiple myeloma.
 
Isatuximab, an intravenous Anti-CD38 antibody being developed by Sanofi and has been designated an orphan drug by the FDA and EMA. In a 57 patient, Phase I, open label trial, treatment with isatuximab/lenalidomid/dexamethasone demonstrated a 56% ORR in relapsed/refractory multiple myeloma. In a 45 patient, Phase Ib, open label trial, treatment with isatuximab/lenalidomid/dexamethasone demonstrated a 62% overall response rate and 18.7-month progression-free survival in relapsed/refractory multiple myeloma. Sanofi announced that in a 307 patient Phase III trial, isatuximab added to pomalidomide and low-dose dexamethasone improved progression free survival compared to pomalidomide and dexamethasone alone in patients with relapsed/refractory multiple myeloma. Sanofi plans to submit and NDA in late 2019. Sanofi has three ongoing Phase III clinical trials evaluating isatuximab in combination with standard care for patients with relapsed/refractory or newly-diagnosed multiple myeloma.
 
Plitidepsin is an oral Apoptosis inducer being developed by PharmaMer and has been designated an orphan drug by the FDA and EMA. PharmaMar announced that in the 255 patient, Phase III ADMYRE trial, where multiple myeloma patients treated with plitidepsin plus dexamethasone had a PFS of 3.8 months compared to 1.9 months with dexamethasone monotherapy and OS of 11.6 months versus 6.4 months. Plitidepsin is also being evaluated for the treatment of angioimmunoblastic T-cell lymphoma. 
 
The most advanced drug being developed for multiple myeloma is selinexor, a Selective Inhibitor of Nuclear Export/ SINE compound being developed by Karyopharm and has been granted orphan drug and Fast Track status by the FDA. Selinexor has a PDUFA date of July 6, 2019. In a 42 patient, Phase II trial, treatment with selinexor in combination with low-dose bortezomib and dexamethasone resulted in a 63% overall response rate and progression-free survival of 9 months in patients with relapsed or refractory multiple myeloma. In a 79 patient, Phase II trial, treatment with selinexor in combination with low-dose bortezomib and dexamethasone resulted in a 21% overall response rate in patients with heavily pretreated, refractory myeloma with limited therapeutic options. Karyopharm announced that in the 122 patient, Phase IIb, STORM trial, treatment with selinexor in combination with dexamethasone resulted in a 26% overall response rate in patients with highly resistant multiple myeloma. An FDA review of selinexor found limited efficacy and significant toxicity in patients with relapsed/refractory multiple myeloma treated with a combination of selinexor dexamethasone. Based on data submitted and historical studies with high-dose dexamethasone, the FDA felt it was difficult to isolate the treatment effect of selinexor. On 2/26/2019, the FDA Oncologic Drugs Advisory Committee recommend a delay in approval of selinexor-dexamethasone to treat triple class-refractory myeloma until after the results of the Phase III BOSTON trial are available in the first half of 2020. In March 2019, the FDA delayed the PDUFA date for selinexor by three months.