Celgene International Sarl Announces Updated Results of its Pivotal Phase III FIRSTTM (MM-020/IFM 07-01) Trial, Comparing Continuous REVLIMID
Jun 12 15
Celgene International Sarl announced updated results of its pivotal phase III FIRSTTM (MM-020/IFM 07-01) trial, comparing continuous REVLIMID® (lenalidomide) plus low-dose dexamethasone (continuous Rd) to a fixed duration of 18 cycles of Rd (72 weeks) (Rd18) or 12 cycles of melphalan, prednisone and thalidomide (72 weeks) (MPT) for the treatment of transplant ineligible patients with newly diagnosed multiple myeloma. The results, as part of the Regulatory submissions which led to the REVLIMID® label expansion in the US and EU in February 2015, were presented during the European Hematology Association annual congress. In the study, the primary endpoint was progression-free survival (PFS) and the primary analysis was between continuous Rd and MPT. Overall survival was a secondary endpoint, along with response rate, duration of response, time to response, safety, time to second-line anti-myeloma treatment and best response achieved to second-line anti-myeloma treatment. An updated analysis of progression-free survival (PFS) demonstrated a median of 26.0 months for patients treated with continuous Rd compared with 21.9 months for MPT (HR 0.69 (95% CI, 0.59-0.80) p=0.00031). The median PFS for Rd18 was 21.0 months. Continuous Rd treatment (doublet regimen) continued to show an OS advantage, with a 25% reduction in risk of death versus the triple-agent MPT regimen in this updated survival analysis (HR 0.75 (95% CI, 0.62-0.90), translating into a median OS improvement of 10.4 months (from 48.5 to 58.9 months). The median OS for Rd18 was 56.7 months. The median follow up was 45.5 months. An updated analysis of safety in the continuous Rd arm remained similar with extended follow-up to previously reported data (N Engl J Med 2014). Those data showed that grade 3/4 adverse events that occurred in at least 8% of patients in the continuous Rd arm, Rd18 arm or MPT arm included neutropenia (28%, 26% and 45%, respectively), anemia (18%, 16% and 19%, respectively), thrombocytopenia (8%, 8% and 11%, respectively), febrile neutropenia (1%, 3% and 3%, respectively), leukopenia (5%, 6% and 10%, respectively), infection (29%, 22% and 17%, respectively), pneumonia (8%, 8% and 6%, respectively), deep-vein thrombosis and/or pulmonary embolism (8%, 6% and 5%, respectively), asthenia (8%, 6% and 6%, respectively), fatigue (7%, 9% and 6%, respectively), and peripheral sensory neuropathy (1%, < 1% and 9%, respectively). An updated analysis of the incidence of invasive second primary malignancies was 3.9% in patients taking continuous Rd, 6.1% in patients taking Rd18 and 5.5% in patients taking MPT. The incidence of solid tumors was similar in the continuous Rd and MPT arms (3.4% and 3.3%, respectively) and 5.9% in the Rd18 arm. In the United States, REVLIMID is approved in combination with dexamethasone for the treatment of patients with multiple myeloma. In the European Union, REVLIMID is approved for the treatment of adult patients with previously untreated multiple myeloma who are not eligible for transplant. REVLIMID is also approved in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy in nearly 70 countries, encompassing Europe, the Americas, the Middle East and Asia, and in combination with dexamethasone for the treatment of patients whose disease has progressed after one therapy in Australia and New Zealand. REVLIMID is also approved in the United States, Canada, Switzerland, Australia, New Zealand and several Latin American countries, as well as Malaysia and Israel, for transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities and in Europe for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate. In addition, REVLIMID is approved in the United States for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib.
Celgene International Sàrl Announces Findings from Long-Term (104-Week) Post-Hoc Analysis of Pooled Data from the PALACE Phase III Clinical Trial Program of Otezla
Jun 9 15
Celgene International Sàrl announced that the findings from a long-term (104-week) post-hoc analysis of pooled data from the PALACE phase III clinical trial program of Otezla® (apremilast) will be presented at the European League Against Rheumatism (EULAR) Annual Congress in Rome, Italy. OTEZLA is the company's oral, selective inhibitor of phosphodiesterase 4 (PDE4) approved for the treatment of adults with active psoriatic arthritis. Dr. Gladman, the lead investigator of the study, will present the analysis of pooled data from the PALACE 1, 2 and 3 phase III clinical trials in which patients with enthesitis and dactylitis at baseline were allowed to be evaluated for the therapeutic benefit of OTEZLA on enthesitis and dactylitis over 104 weeks. In the PALACE trials, patients were randomized to receive either OTEZLA 20 mg twice daily, OTEZLA 30 mg twice daily or identically appearing placebo for the first 16 weeks. At week 16, some placebo-treated patients were randomized to one of the two OTEZLA groups, while others remained on placebo through week 24. At week 24, patients either continued on OTEZLA or were switched from placebo to OTEZLA 20 mg or 30 mg twice daily in a long term, open-label, active treatment phase. Although enthesitis and dactylitis involvement were not required for patients to enter the study, and patients were not stratified according to baseline enthesitis or dactylitis, approximately 63% (945/1,493) of patients had pre-existing enthesitis at baseline and approximately 42% (633/1,493) of patients had pre-existing dactylitis at baseline. A post-hoc analysis on the effect of OTEZLA on enthesitis and dactylitis in patients with pre-existing enthesitis or dactylitis was performed on as-observed pooled data from PALACE 1, 2 and 3. The study abstract states that treatment with OTEZLA 30 mg twice daily in patients with pre-existing enthesitis (inflammation at sites where tendons or ligaments insert into bone) or dactylitis (inflammation of an entire digit) — two distinct manifestations of psoriatic arthritis — demonstrated improvements in these symptoms at 52 weeks and that improvements were sustained through week 104. For patients taking OTEZLA 30 mg twice daily, the mean Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) was reduced by 43.5% at week 52 (n=377) and by 57.5% at week 104 (n=302). A score of 0, indicating no pain at any of the sites assessed, was achieved by 37.7% of patients at week 52 and 48.7% at week 104. OTEZLA 30 mg twice daily also resulted in a mean 67.9% decrease in dactylitis count at week 52 (n=249) and 80.0% decrease at week 104 (n=200). A dactylitis count of 0, indicating no signs of dactylitis, was achieved by 67.5% of patients at week 52 and 77.5% of patients at week 104. During weeks 0 to 52, adverse events (AEs) occurring in at least 5% of patients treated with OTEZLA were diarrhea, nausea, headache, upper respiratory tract infection (URTI) and nasopharyngitis. Rates of URTI, nasopharyngitis, diarrhea, nausea and headache between weeks 52 and 104 were 6.5%, 5.8%, 2.9%, 1.8% and 3.0%, respectively. No new safety concerns were identified, and no increases were seen in AE incidence or severity with longer exposure.
Italian Authorities Approves Celgene International Sarl's ABRAXANE, as a First-Line Treatment of Adult Patients with Metastatic Pancreatic Cancer
Feb 24 15
Celgene International Sarl announced that Italian authorities have issued a positive decision for NHS reimbursement of ABRAXANE® (paclitaxel formulated as albumin-bound nanoparticles, or nab-paclitaxel) in combination with gemcitabine, for the first-line treatment of patients with metastatic adenocarcinoma of the pancreas, or pancreatic cancer. For the first time in this disease, the Italian Medicines Agency (AIFA) has recognised the important innovation that ABRAXANE brings as a therapeutic treatment for pancreatic cancer. The reimbursement decision has been published in the Italian Official Gazette no. 30, dated 6 February 2015, and it follows the December 2013European Commission (EC) approval of ABRAXANE for this indication. ABRAXANE has been available and reimbursed in Italy for the treatment of metastatic breast cancer since 2011. During the last few decades, little progress has been made in improving outcomes for patients diagnosed with pancreatic cancer. The mortality of pancreatic cancer is high, making it the fourth deadliest cancer for both men and women.1 Patients diagnosed with metastatic disease have a median life expectancy, after diagnosis, of approximately three to six months. There have been no new medications approved for pancreatic cancer in eight years.