Summit, NJ (Press Release) – Celgene Corpo­ra­tion (NASDAQ:CELG) today announced it has fulfilled the accelerated approval require­ments for POMALYST® (poma­lido­mide) based on results from MM-003, an inter­na­tional phase III study of POMALYST plus low-dose dex­a­meth­a­sone versus high-dose dex­a­meth­a­sone in re­lapsed / refractory multiple myeloma patients. POMALYST, in com­bi­na­tion with dex­a­meth­a­sone is ap­proved for patients with multiple myeloma who have received at least two prior ther­a­pies in­­clud­ing lena­lido­mide and a pro­te­a­some inhibitor and have dem­onstrated disease pro­gres­sion on or within 60 days of com­ple­tion of the last ther­apy.

"There remains a sig­nif­i­cant unmet need for re­lapsed / refractory multiple myeloma patients. POMALYST has been able to help thousands of patients since its approval in 2013 and this data now con­firms its survival benefits," said Jacqualyn A. Fouse, Ph.D., Pres­i­dent, Global Hematology and Oncology for Celgene. "This label update provides im­por­tant in­­for­ma­tion about a key prod­uct in our industry-leading portfolio of ther­a­pies for patients with multiple myeloma."

In the MM-003 study, median pro­gres­sion-free survival (PFS), the pri­mary end­point of the study, was sig­nif­i­cant­ly longer with POMALYST plus low-dose dex­a­meth­a­sone (3.6 months) than high-dose dex­a­meth­a­sone (1.8 months: HR 0.45 two-sided 95% CI: 0.35-0.59 p < 0.001). Patients in the POMALYST plus low-dex­a­meth­a­sone arm had a 55% reduction in the risk of pro­gres­sion or death.

The pre-specified, final analysis for over­all survival (OS) showed a median OS for the POMALYST plus low-dose dex­a­meth­a­sone arm of 12.4 months (95% CI: 10.4, 15.3), compared to the high-dose dex­a­meth­a­sone arm of 8 months (95% CI: 6.9, 9.0). This survival benefit was statistically sig­nif­i­cant (HR 0.70 [two-sided 95% CI: 0.54, 0.92], p=0.009) even though 53% of patients in the high-dose dex­a­meth­a­sone arm had sub­se­quent­ly received POMALYST. The hazard ratio of 0.70 equated to a 30% reduction in the risk of death for patients receiving POMALYST plus low-dose dex­a­meth­a­sone. Median PFS and OS were based on the assess­ment of an Independent Review Adjudication Committee.

POMALYST was initially approved by the FDA in February 2013 under the agency's accelerated approval pro­gram based on the phase II study, MM-002.

POMALYST® (poma­lido­mide) is a thalido­mide analogue indicated, in com­bi­na­tion with dex­a­meth­a­sone, for patients with multiple myeloma who have received at least two prior ther­a­pies in­­clud­ing lena­lido­mide and a pro­te­a­some inhibitor and have dem­onstrated disease pro­gres­sion on or within 60 days of completion of the last ther­apy.

Important Safety Information

Embryo-Fetal Toxicity

• POMALYST is contraindicated in pregnancy. POMALYST is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting POMALYST treatment.
• Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping POMALYST treatment.

POMALYST is only avail­able through a restricted distribution pro­gram called POMALYST REMS®.

Venous and Arterial Thromboembolism

• Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with POMALYST. Prophylactic antithrombotic measures were employed in clinical trials. Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient's underlying risk factors.

• POMALYST can cause fetal harm and is contraindicated in females who are pregnant. If POMALYST is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity

• Females of Reproductive Potential: Must avoid pregnancy while taking POMALYST and for at least 4 weeks after completing therapy. Must commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control, beginning 4 weeks prior to initiating treatment with POMALYST, during therapy, during dose interruptions, and continuing for 4 weeks following dis­con­tin­u­a­tion of POMALYST therapy. Must obtain 2 negative pregnancy tests prior to initiating ther­a­py
• Males: Pomalidomide is present in the semen of patients receiving the drug. Males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 28 days after discontinuing POMALYST, even if they have undergone a successful vasectomy. Males must not donate sperm
• Blood Donation: Patients must not donate blood during treatment with POMALYST and for 1 month following discontinuation of POMALYST therapy because the blood might be given to a pregnant female patient whose fetus must not be exposed to POMALYST

POMALYST REMS® Program

Because of the embryo-fetal risk, POMALYST is avail­able only through a restricted pro­gram under a Risk Evaluation and Mitigation Strategy (REMS) called "POMALYST REMS®." Prescribers and pharmacies must be certified with the pro­gram; patients must sign an agree­ment form and comply with the require­ments. Further in­­for­ma­tion about the POMALYST REMS® pro­gram is avail­able at www.CelgeneRiskManagement.com or by telephone at 1-888-423-5436.

Venous and Arterial Thromboembolism: Venous throm­bo­em­bol­ic events (DVT and PE) and arterial throm­bo­em­bol­ic events (ATE) (myocardial infarction and stroke) have been observed in patients treated with POMALYST. In Trial 2, where anticoagulant ther­a­pies were mandated, throm­bo­em­bol­ic events occurred in 8.0% of patients treated with POMALYST and low dose-dex­a­meth­a­sone (Low-dose Dex) vs 3.3% treated with high-dose dex­a­meth­a­sone. Venous throm­bo­em­bol­ic events (VTE) occurred in 4.7% of patients treated with POMALYST and Low-dose Dex vs 1.3% treated with high-dose dex­a­meth­a­sone. Arterial throm­bo­em­bol­ic events in­clude terms for arterial throm­bo­em­bol­ic events, is­chem­ic cerebrovascular con­di­tions, and is­chem­ic heart disease. Arterial throm­bo­em­bol­ic events occurred in 3.0% of patients treated with POMALYST and Low-dose Dex vs 1.3% treated with high-dose dex­a­meth­a­sone. Patients with known risk factors, in­­clud­ing prior thrombosis, may be at greater risk, and actions should be taken to try to minimize all modifiable factors (e.g., hyperlipidemia, hyper­tension, smoking).

Hematologic Toxicity: In trials 1 and 2 in patients who received POMALYST + Low-dose Dex, neu­tro­penia (46%) was the most frequently reported Grade 3/4 adverse reac­tion, followed by anemia and throm­bo­cyto­pe­nia. Monitor patients for hema­to­logic toxicities, especially neu­tro­penia. Monitor com­plete blood counts weekly for the first 8 weeks and monthly therafter. Patients may require dose inter­rup­tion and/or modification.

Hepatotoxicity: Hepatic failure, in­­clud­ing fatal cases, has occurred in patients treated with POMALYST. Elevated levels of alanine amino­trans­ferase and bilirubin have also been observed in patients treated with POMALYST. Monitor liver function tests monthly. Stop POMALYST upon elevation of liver enzymes. After return to base­line values, treat­ment at a lower dose may be con­sidered.

Hypersensitivity Reactions: Angioedema and severe dermatologic reac­tions have been reported. Dis­con­tinue POMALYST for angioedema, skin exfoliation, bullae, or any other severe dermatologic reac­tions, and do not resume ther­apy.

Dizziness and Confusional State: In trials 1 and 2 in patients who received POMALYST + Low-dose Dex, 14% ex­peri­enced dizzi­ness and 7% a confusional state; 1% of patients ex­peri­enced Grade 3 or 4 dizzi­ness and 3% ex­peri­enced a Grade 3 or 4 confusional state. Instruct patients to avoid situations where dizzi­ness or confusional state may be a problem and not to take other medications that may cause dizzi­ness or con­fu­sion­al state without adequate medical advice.

Neuropathy: In trials 1 and 2, patients who received POMALYST + Low-dose Dex ex­peri­enced neu­rop­athy (18%) and periph­eral neu­rop­athy (~12%). In trial 2, 2% of patients ex­peri­enced Grade 3 neu­rop­athy.

Risk of Second Primary Malignancies: Cases of acute mye­log­e­nous leukemia have been reported in patients receiving POMALYST as an inves­ti­ga­tional ther­apy outside of multiple myeloma.

Tumor Lysis Syndrome: Tumor lysis syn­drome (TLS) may occur in patients treated with POMALYST. Patients at risk are those with high tumor burden prior to treat­ment. These patients should be monitored closely and appro­pri­ate precautions taken.

ADVERSE REACTIONS

Nearly all patients treated with POMALYST + Low-dose Dex ex­peri­enced at least one adverse reac­tion (99%). In trial 2, the most common adverse reac­tions in­cluded neu­tro­penia (51.3%), fatigue and asthenia (46.7%), upper res­pira­tory tract in­fec­tion (31%), thrombo­cytopenia (29.7%), pyrexia (26.7%), dyspnea (25.3%), diarrhea (22%), con­sti­pa­tion (21.7%), back pain (19.7%), cough (20%), pneu­monia (19.3%), edema periph­eral (17.3%), periph­eral neu­rop­athy (17.3%), bone pain (18%), nausea (15%), and muscle spasms (15.3%). Grade 3 or 4 adverse reac­tions in­cluded neu­tro­penia (48.3%), thrombo­cytopenia (22%), and pneu­monia (15.7%).

DRUG INTERACTIONS

Pomalidomide is primarily metabolized by CYP1A2 and CYP3A. Pomalidomide is also a substrate for P-glycoprotein (P-gp). Avoid the use of strong CYP1A2 inhibitors. If medically nec­es­sary to co-administer strong inhibitors of CYP1A2 in the presence of strong inhibitors of CYP3A4 and P-gp, reduce POMALYST dose by 50%. Cigarette smoking may reduce poma­lido­mide exposure due to CYP1A2 induction. Patients should be advised that smoking may reduce the efficacy of poma­lido­mide.

USE IN SPECIFIC POPULATIONS

Pregnancy: If pregnancy does occur during treat­ment, im­medi­ately dis­con­tinue the drug and refer patient to an obstetrician/gynecologist ex­peri­enced in reproductive toxicity for further evaluation and counseling. Report any sus­pected fetal exposure to POMALYST to the FDA via the MedWatch pro­gram at 1-800-332-1088 and also to Celgene Corpo­ra­tion at 1-888-423-5436.

Nursing Mothers: It is not known if poma­lido­mide is excreted in human milk. Pomalidomide was excreted in the milk of lactating rats. Because many drugs are excreted in human milk and because of the poten­tial for adverse reac­tions in nursing infants from POMALYST, a de­ci­sion should be made whether to dis­con­tinue nursing or to dis­con­tinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use: Safety and effectiveness of POMALYST in patients under the age of 18 have not been estab­lish­ed.

Geriatric Use: No dosage ad­just­ment is required for POMALYST based on age. Patients > 65 years of age were more likely than patients ≤65 years of age to ex­peri­ence pneu­monia.

Renal and Hepatic Impairment: Pomalidomide is metabolized in the liver. Pomalidomide and its me­tab­o­lites are primarily excreted by the kidneys. The influence of renal and hepatic im­pair­ment on the safety, ef­fica­cy, and phar­maco­kinetics of poma­lido­mide has not been eval­u­ated. Avoid POMALYST in patients with a serum creatinine > 3.0 mg/dL. Avoid POMALYST in patients with serum bilirubin > 2.0 mg/dL and AST/ALT > 3.0 x ULN.

Please see full Prescribing Information, in­­clud­ing Boxed WARNINGS.

About MM-003

MM-003 was a Phase III multi-center, ran­dom­ized, open-label study where POMALYST + low-dose dex­a­meth­a­sone ther­apy was compared to high-dose dex­a­meth­a­sone in adult patients with re­lapsed and re­frac­to­ry multiple myeloma, who had received at least two prior treat­ment regi­mens, in­­clud­ing lena­lido­mide and bor­tez­o­mib, and dem­onstrated disease pro­gres­sion on or within 60 days of the last ther­apy. For patients receiv­ing POMALYST + low-dose dexamathasone, 94% were refractory to lena­lido­mide, and 74% were refractory to both lena­lido­mide and bor­tez­o­mib. Patients with creatinine clearance ≥ 45ml/min qualified for the study. A total of 455 patients were enrolled in the study: 302 in the POMALYST + low-dose dex­a­meth­a­sone arm and 153 in the high-dose dex­a­meth­a­sone arm. Patients in the POMALYST + low-dose dex­a­meth­a­sone arm were admin­istered 4 mg POMALYST orally on days 1 to 21 of each 28-day cycle. Dexamethasone (40 mg) was admin­istered once per day on days 1, 8, 15 and 22 of a 28-day cycle. Patients > 75 years of age started treat­ment with 20 mg dex­a­meth­a­sone using the same schedule. For the high-dose dex­a­meth­a­sone arm, dex­a­meth­a­sone (40 mg) was admin­istered once per day on days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle. Patients > 75 years of age started treat­ment with 20 mg dex­a­meth­a­sone using the same schedule. Treatment con­tinued until patients had disease pro­gres­sion.

About POMALYST®

POMALYST is a thalido­mide analogue indicated in com­bi­na­tion with dex­a­meth­a­sone for patients with multiple myeloma who have received at least two prior ther­a­pies in­­clud­ing lena­lido­mide and a pro­te­a­some inhibitor and have dem­onstrated disease pro­gres­sion on or within 60 days of completion of the last ther­apy.

Please see full Prescribing Information, in­­clud­ing Boxed WARNINGS.

About Celgene

Celgene Corpo­ra­tion, headquartered in Summit, New Jersey, is an integrated global pharma­ceu­tical com­pa­ny engaged primarily in the discovery, devel­op­ment and com­mer­cial­iza­tion of inno­va­tive ther­a­pies for the treat­ment of cancer and inflammatory diseases through gene and protein reg­u­la­tion. For more infor­ma­tion, please visit www.celgene.com. Follow Celgene on Twitter @Celgene, and on Pinterest and LinkedIn.

POMALYST® is a registered trademark of Celgene Corpo­ra­tion.

Forward-Looking Statements

This press release may con­tain forward-looking state­ments, which are generally state­ments that are not historical facts. Forward-looking state­ments can be identified by the words "expects," "antic­i­pates," "believes," "intends," "estimates," "plans," "will," "outlook" and similar ex­pres­sions. Forward-looking state­ments are based on man­agement's current plans, esti­mates, assump­tions and projections, and speak only as of the date they are made. We under­take no obli­ga­tion to update any forward-looking state­ment in light of new in­­for­ma­tion or future events, except as other­wise required by law. Forward-looking state­ments involve in­her­ent risks and un­cer­tain­ties, most of which are dif­fi­cult to predict and are generally beyond our control. Actual results or out­comes may differ ma­teri­ally from those implied by the forward-looking state­ments as a result of the impact of a number of factors, many of which are discussed in more detail in our Annual Report on Form 10-K and other reports filed with the Securities and Exchange Com­mis­sion.

Source: Celgene.