Celgene Corp's positive run of late-stage data has continued over the last week with the firm presenting positive results for apremilast in psoriatic arthritis and pomalidomide for multiple myeloma.
First up, last week saw the firm present the full set of data from the PALACE-1 study of apremilast at the American College of Rheumatology meeting in Washington DC. Celgene had previously announced statistical significance for the primary endpoint of ACR20 (ie a 20% improvement in their condition) for patients receiving the oral small-molecule inhibitor of phosphodiesterase 4 in the first of three Phase III studies.
PALACE-1 evaluated apremilast in patients with PsA who had received oral disease-modifying antirheumatic drugs (DMARD) and/or biologic therapy and/or had failed on an injectable tumour necrosis factor (TNF) inhibitors, notably Abbott's Humira (adalimumab) and Pfizer/Amgen's Enbrel (etanercept).
In the study, apremilast demonstrated statistically significant and higher ACR20 responses at week 16 in patients receiving either apremilast 20 or 30 mg twice-day (BID) monotherapy (31.5% and 50.8% respectively versus 10.5% for placebo, with no meaningful advantage to adding oral DMARDs to the Celgene drug. A higher ACR20 response at week 16 was also demonstrated in biologic-naive subjects receiving apremilast 30 mg BID compared with placebo (59% vs 12%).
The company also noted that "a robust and consistent response" across all arthritis-related secondary endpoints, including ACR50, ACR70 and other commonly-used measurements were seen at week 24. Statistically significant results were also demonstrated in physical function at week 16 and were maintained at week 24.
Interestingly, the safety profile was impressive, and Arthur Kavanaugh of the University of California, San Diego, told journalists in Washington that no opportunistic infections (including tuberculosis) or lymphoma were observed through week 24. Apremilast was generally well tolerated and the majority of adverse events were mild or moderate. Dr Kavanaugh added that most were "a nuisance but not serious" and were resolved after a month of therapy.
Based on the PALACE programme, Celgene intends to file apremilast with the US Food and Drug Administration in the first half of 2013 and a submission for psoriasis is expected in the second half. A filing in Europe is also planned for the second half of 2013.
Doctors attending the ACR meeting seemed impressed with the data but some noted that it was not as robust as that seen for biologics in terms of ACR20. A French rheumatologist told PharmaTimes World News that apremilast could benefit from being well-tolerated but expressed his concern that only about 20% of patients experienced a 50% improvement in symptoms, and just 11% hit the ACR70 level.
Strong survival data for pomalidomide
Meantime, Celgene has also noted that a data safety monitoring board has found that a Phase III study of pomalidomide met its primary endpoint by demonstrating a significant improvement in progression-free survival for patients with multiple myeloma.
The study, MM-003, demonstrated statistically significantly improved PFS in patients with relapsed and/or refractory multiple myeloma on pomalidomide with low-dose dexamethasone, in comparison with those who took high-dose dexamethasone alone. Also at the overall survival interim analysis, the data looks promising and the DSMB has recommended that patients in the dexamethasone arm who had not yet progressed should cross over to pomalidomide.
Full data on pomalidomide will be presented at the American Society of Hematology meeting in Atlanta next month. A decision on Celgene’s New Drug Application for the treatment is expected by February 10.
The promising results for apremilast and pomalidomide comes in the wake of positive Phase III data which shows that Abraxane (nanoparticle albumin-bound -'nab' - paclitaxel), currently approved for breast and lung cancer, extends survival in patients with advanced pancreatic cancer.