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FDA Expands Indication for Revlimid (lenalidomide) as a Maintenance Treatment for Patients with Multiple Myeloma Following Autologous Hematopoietic Stem Cell Transplant (auto-HSCT)

SUMMIT, N.J.--(BUSINESS WIRE) February 22,2017 -- Celgene Corporation (NASDAQ:CELG) today announced that the U.S. Food and Drug Administration (FDA) has expanded the existing indication for Revlimid (lenalidomide) 10 mg capsules to include use for patients with multiple myeloma as maintenance therapy following autologous hematopoietic stem cell transplant (auto-HSCT). The expanded indication makes Revlimid the first and only treatment to receive FDA approval for maintenance use following auto-HSCT.

"Autologous stem cell transplant after induction therapy is part of the continuum of care for transplant-eligible multiple myeloma patients. However, most patients will still see their disease recur or progress after this treatment," said Philip McCarthy, M.D., Director, Blood and Marrow Transplant Center, Department of Medicine at Roswell Park Cancer Institute. "Lenalidomide maintenance therapy, which has been shown to increase progression-free survival following autologous stem cell transplant in clinical trials can be considered a standard of care for these patients."

The approval was based on two large studies including more than 1,000 patients comparing Revlimid maintenance therapy given until disease progression or unacceptable toxicity after auto-HSCT versus no maintenance. In both studies, the primary efficacy endpoint was progression-free survival (PFS) defined from randomization to the date of progression or death, whichever occurred first. In the most current PFS analysis, Study 1 (U.S.-based NCI sponsored cooperative group study CALGB 100104) demonstrated a median PFS of 5.7 years (95% CI: 4.4-not estimable) versus 1.9 years (95% CI: 1.6-2.5) for no maintenance, a difference of 3.8 years (HR 0.38 [95% CI: 0.28-0.50]). Study 2 (European-based study IFM 2005-02) also showed a benefit with a median PFS of 3.9 years (95% CI: 3.3-4.7) versus 2 years (95% CI: 1.8-2.3) for no maintenance, a difference of 1.9 years (HR 0.53 [95% CI: 0.44-0.64]). Individual studies were not powered for an overall survival endpoint. A descriptive analysis showed the median overall survival in Study 1 was 9.3 years (95% CI: 8.5-not estimable) for patients who received Revlimid versus 7 years (95% CI: 5.9-8.6) for no maintenance (HR 0.59 [95% CI: 0.44-0.78]). In Study 2, median overall survival was 8.8 years (95% CI: 7.4-not estimable) for patients who received Revlimid versus 7.3 years (95% CI: 6.7-9.0) for no maintenance (HR 0.90 [95% CI: 0.72-1.13]).

"In newly-diagnosed multiple myeloma, auto-HSCT remains a viable option for many patients and often provides a strong response against the disease," said Michael Pehl, President, Global Hematology and Oncology for Celgene. "By expanding the approval for Revlimid to include post-transplant maintenance, patients have the potential to maintain those responses and, importantly, delay progression of the disease."

As described in the prescribing information, Revlimid can cause fetal harm and is contraindicated in females who are pregnant. Revlimid is only available through a restricted distribution program, Revlimid REMS®. Deep vein thrombosis, pulmonary embolism, myocardial infarction and stroke occur in patients with MM treatment with Revlimid and thromboprophylaxis is recommended.

The most frequently reported adverse reactions in ≥20% (Revlimid arm) across both maintenance studies (Study 1, Study 2 respectively) were neutropenia (79%, 61%), thrombocytopenia (72%, 24%), leukopenia (23%, 32%), anemia (21%, 9%), upper respiratory tract infection (27%, 11%), bronchitis (5%, 47%), nasopharyngitis (2%, 35%), cough (10%, 27%), gastroenteritis (0%, 23%), diarrhea (55%, 39%), rash (32%, 8%), fatigue (23%, 11%), asthenia (0%, 30%), muscle spasm (0%, 33%) and pyrexia (8%, 21%). The most frequently reported Grade 3 or 4 reactions (more than 20% in the Revlimid arm) included neutropenia, thrombocytopenia, and leukopenia.

The frequencies of onset of adverse reactions were generally highest in the first six months of treatment and then the frequencies decreased over time or remained stable throughout treatment.

In patients receiving Revlimid maintenance therapy, hematologic second primary malignancies (SPM) occurred in 7.5% of patients compared to 3.3% in patients receiving placebo. The incidence of hematologic plus solid tumor (excluding squamous cell carcinoma and basal cell carcinoma) SPM was 14.9%, compared to 8.8% in patients receiving placebo with a median follow-up of 91.5 months. Non-melanoma skin cancer SPM, including squamous cell carcinoma and basal cell carcinoma, occurred in 3.9% of patients receiving Revlimid maintenance, compared to 2.6% in the placebo arm. Patients should be monitored for the development of second primary malignancies. Take into account both the potential benefit of Revlimid and the risk of second primary malignancies when considering treatment with Revlimid.

Revlimid in combination with dexamethasone was previously approved in June 2006 for use in patients with multiple myeloma who have received at least one prior therapy, and the indication expanded in February 2015 to include patients newly diagnosed with multiple myeloma.

In June 2016, an application was submitted to the European Medicines Agency (EMA) for the review of Revlimid as maintenance treatment in NDMM patients after receiving an autologous stem cell transplant. In January 2017, the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for the use of Revlimid as monotherapy for the maintenance treatment of adult patients with newly diagnosed multiple myeloma (MM) who have undergone autologous stem cell transplantation.

About CALGB 100104 (Study 1)

CALGB 100104 was a phase III, randomized, controlled, double-blind, multi-center study conducted in 47 centers by the CALGB, which is now part of the Alliance for Clinical Trials in Oncology, a US national oncology cooperative group. 460 newly diagnosed multiple myeloma patients - aged between 18 and 70 years (CLcr ≥ 30 mL/min) - who had undergone induction therapy within 12 months of diagnosis and achieved at least stable disease (SD) or better 90-100 days following autologous stem cell transplant (ASCT), were randomized to receive either Revlimid maintenance or placebo. The Revlimid maintenance dose was 10 mg/day (after 3 months increased to 15 mg/day if tolerated) until disease progression, intolerable side effects, patient withdrawal for another reason, or death. The dose was reduced, or treatment was temporarily interrupted or stopped, as needed to manage toxicity. A dose increase to 15 mg once daily occurred in 135 patients (58%).

About IFM 2005-02 (Study 2)

IFM 2005-02 was a phase III, controlled, double-blind, multi-center study conducted by the University Hospital of Toulouse in concert with the IFM, an independent French myeloma cooperative group, at 78 centers in France, Belgium, and Switzerland. 614 newly diagnosed multiple myeloma patients younger than 65 years (CLcr ≥ 30 mL/min) who had undergone induction therapy and did not present with signs of disease progression within 6 months of undergoing ASCT. Patients were then randomized to receive a two-month consolidation regimen of Revlimid monotherapy 25 mg per day on 21/28 days, followed by either Revlimid maintenance or placebo. The Revlimid dose was 10 mg/day (after 3 months increased to15 mg/day if tolerated) until disease progression, intolerable side effects, patient withdrawal for another reason or death. The dose was reduced, or treatment was temporarily interrupted or stopped, as needed to manage toxicity. A dose increase to 15 mg once daily occurred in 185 patients (60%).

About Celgene

Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through next-generation solutions in protein homeostasis, immuno-oncology, epigenetics, immunology and neuro-inflammation. For more information, please visit Follow Celgene on Social Media: @Celgene, Pinterest, LinkedIn, Facebook and YouTube.

Forward-Looking Statements

This press release contains 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 our other reports filed with the Securities and Exchange Commission.

Source: Celgene Corporation

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