POMALYST?, in combination with bortezomib and dexamethasone,?provides a new medication option for patients living with multiple myeloma

TORONTO,?July 10, 2019?/CNW/ - Celgene Inc. announced today that Health Canada has approved a POMALYST?(pomalidomide)-based triplet combination with bortezomib and dexamethasone. This is a new treatment option for patients with multiple myeloma (MM) who have received at least one prior treatment regimen that included REVLIMID?(lenalidomide).

POMALYST??is an oral medication taken daily and is indicated, in combination with bortezomib and dexamethasone, for the treatment of adult patients with MM who have received at least one prior treatment regimen that included lenalidomide.1,2

"The treatment landscape for multiple myeloma has significantly changed over the years. New treatment options like this POMALYST?-based triplet combination allow patients and their physicians to work together to find the best early-line treatment regimen," says Dr. Reece, Princess Margaret Cancer Centre. "In the pivotal clinical trial, OPTIMISMM, we saw the POMALYST?-based triplet combination improve and provide a sustained progression-free survival for multiple myeloma patients who were exposed to, and for the most part refractory to lenalidomide. This is important, as over the last few years lenalidomide has become a standard of care in front-line treatment of multiple myeloma in?Canada?and until OPTIMISMM, the patient population exposed or refractory to lenalidomide in front line was not well studied. The POMALYST?-based triplet combination is a positive step forward in the treatment journey for multiple myeloma patients and their loved ones."

MM is an increasingly prevalent blood cancer originating from bone marrow plasma cells.3?In?Canada, the number of patients living with the disease is on the rise, with eight Canadians diagnosed each day.4

"Multiple myeloma is a complex disease which can impact each patient differently," says?Martine Elias, Executive Director, Myeloma Canada. "It is encouraging to see how new treatment options, like the POMALYST?-based triplet combination, successfully treat Canadian myeloma patients."

Health?Canada's?approval of the POMALYST?-based triplet combination with bortezomib and dexamethasone is based on OPTIMISMM, the first prospective phase 3 trial, including 559 MM patients, to evaluate a POMALYST?-containing triplet regimen in patients.5?Patients participating in this trial were all previously treated with REVLIMID??and the majority, 70 per cent, were REVLIMID??refractory.6,7?All patients had received 1-3 prior antimyeloma regimens and demonstrated disease progression on or after the last therapy.8

Patients who received the POMALYST?-based triplet combination with bortezomib and dexamethasone in the clinical trial had a significantly longer progression-free survival (PFS) of 4.1 months more than those who received only bortezomib and dexamethasone (median PFS 11.2 months versus 7.1 months, respectively).9,10

About Multiple Myeloma

MM is a life-threatening blood cancer characterized by tumor proliferation and suppression of the immune system.11,12?It is a rare but deadly disease ? around 2,900 people are diagnosed with MM in?Canada?and 1,450 Canadians die from the disease each year.13?The typical MM disease course includes periods of symptomatic myeloma followed by periods of remission, and eventually, the disease becomes refractory (non-responsive).14?While all MM patients may experience different symptoms during and after treatment, patients may also experience physical issues.15?These may include bone complications, anemia, infections, kidney damage, high blood calcium and other blood complications, osteonecrosis of the jaw, side effects of medication, as well as bone pain, nerve pain and neuropathy.16?MM patients may also experience emotional health issues, with 40 per cent of cancer patients experiencing depression or anxiety.17

About OPTIMISMM

OPTIMISMM is the first phase 3 trial designed to compare the safety and efficacy of a POMALYST?-based triplet combination with bortezomib and dexamethasone versus only bortezomib and dexamethasone as an early line of therapy in patients with relapsed or refractory multiple myeloma (with 1-3 prior regimens of therapy) and prior REVLIMID??exposure, including REVLIMID?-refractory patients.

This multi-center, international, open-label, randomized phase 3 clinical trial included 559 patients (281 patients in the POMALYST?-based triplet combination with bortezomib and dexamethasone arm and 278 in the bortezomib and dexamethasone arm). Demographic, baseline, and prior disease characteristics were generally well balanced between the two treatment arms. All patients had prior treatment with REVLIMID?, with the majority being REVLIMID??refractory (71 per cent in the POMALYST?-based triplet combination arm versus 69 per cent in the bortezomib and dexamethasone arm) and 70 per cent versus 66 per cent, respectively, were refractory to their last treatment. Median follow-up was 16 months.

Results from OPTIMISMM showed that patients receiving the POMALYST?-based triplet combination with bortezomib and dexamethasone treatment achieved a significantly longer PFS than those in the bortezomib and dexamethasone treatment arm (11.20 months versus 7.10 months, respectively [HR 0.61, p= < 0.0001; 95 per cent CI: (0.49-0.77)]), reducing the risk of disease progression by 39 per cent in the POMALYST?-based triplet combination arm. In an exploratory sub-group analysis of patients with one prior line of therapy, median progression-free survival with the POMALYST?-based triplet combination with bortezomib and dexamethasone was 20.73 months versus 11.63 months with bortezomib and dexamethasone (HR 0.54; 95 per cent CI: 0.36, 0.82).

Patients were stratified based on age (<?75 years old versus 75 years old), number of prior anti-myeloma regiments (1 vs. > 1) and ?2-microglobulin levels (<3.5 mg/L versus?>?3.5 to?<?5.5 mg/L versus > 5.5 mg/L). Patients were randomized 1:1 to receive the POMALYST?-based triplet combination with bortezomib and dexamethasone or bortezomib and dexamethasone. In 21-day cycles, patients received POMALYST??4 mg on days 1-14 (POMALYST?-based triplet combination arm only); bortezomib 1.3 mg/m2?on days 1, 4, 8 and 11 for cycles 1-8 and on days 1 and 8 for cycles 9 and onwards; and dexamethasone 20 mg/day (10 mg if aged > 75 years) on the days of and after receiving bortezomib treatment.

About Celgene's Immunomodulatory Drugs

IMiD??agents are Celgene's proprietary small molecule, orally available compounds for the treatment of some blood cancers. IMiD??agents are hypothesized to have multiple mechanisms of action. They have been found to enhance T cells and (NK) cell-mediated immunity. In addition to immunomodulatory properties, IMiD??agents are hypothesized to have tumoricidal and antiangiogenic activity. Celgene's portfolio of IMiD??agents have become a foundation of multiple myeloma research, with a growing number of studies exploring these compounds as combination partners across a range of settings of the disease.

About POMALYST??(pomalidomide)

POMALYST??in combination with bortezomib and dexamethasone is indicated in the treatment of adult patients with MM who have received at least one prior treatment regimen that included lenalidomide. It belongs to a group of drugs called immunomodulatory drugs (IMiDs?).

About Celgene

Celgene is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of novel therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit the company's website at?www.celgene.ca.

Indications and Clinical Use:

POMALYST??in combination with dexamethasone and bortezomib is indicated in the treatment of adult patients with MM who have received at least one prior treatment regimen that included lenalidomide.

POMALYST??in combination with dexamethasone is indicated for patients with multiple myeloma for whom both bortezomib and lenalidomide have failed and who have received at least two prior treatment regimens and have demonstrated disease progression on the last regimen.

Geriatrics (> 65 years of age):

Concomitant administration of dexamethasone may increase the risk of infection, particularly pneumonia; dexamethasone dosing may need to be reduced or interrupted in case of infection. Reduce dexamethasone dose by half in patients >75 years of age.

Contraindications:

• Pregnant women and women at risk of becoming pregnant
• Breastfeeding women
• Male patients unable to follow or comply with the required contraceptive measures
• Hypersensitivity to POMALYST?, thalidomide, lenalidomide or to any ingredient in the formulation or component of the container

Controlled Distribution Program:

Available only through a controlled distribution program called RevAid?

Serious warnings and precautions:

• POMALYST??should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents.
• Pregnancy:?Potential for human birth defects, stillbirths, and spontaneous abortions
• Hematologic:?Neutropenia and thrombocytopenia
• Infections,?including fatal cases
• Venous thromboembolism:?Deep vein thrombosis (DVT) and pulmonary embolism (PE)
• Hepatic:?Hepatotoxicity, including fatal cases
• Hepatitis B virus reactivation, including fatal cases
• Severe dermatologic reactions:?Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS), including fatal cases
• Tumour lysis syndrome,?including fatal cases

Other Relevant Warnings and Precautions:

• Cardiovascular disorders
• Second primary malignancies
• Immune reactions: Use in patients with active hepatitis A, B, or C infection; hypersensitivity reactions (angioedema, urticaria)
• Interstitial lung disease
• Neurologic: Possible impairment of mental and/or physical abilities; peripheral neuropathy
• Use in hepatic impairment or renal impairment
• Monitoring and Laboratory testing required
• Combination treatment with bortezomib; consult bortezomib Product Monograph prior to initiating treatment

For More Information:

Please consult the Product Monograph at pomalystpm.ca for important information relating to adverse reactions, drug interactions and dosing information. The Product Monograph is also available by calling 1-877-923-5436.