publication date: Feb. 24, 2017
Drugs and Targets
FDA approves Revlimid as maintenance in multiple myeloma following transplant
FDA approved lenalidomide (Revlimid) as maintenance therapy for patients with multiple myeloma following autologous stem cell transplant.
The drug is sponsored by Celgene Corp.
In 2006, lenalidomide, an orally administered thalidomide analogue, received FDA approval for use with dexamethasone in patients with multiple myeloma who received at least one prior therapy. In 2015, the indication was expanded for use in combination with dexamethasone for the treatment of patients with multiple myeloma, to include newly diagnosed multiple myeloma patients who are not eligible for autologous stem cell transplant. Lenalidomide is also approved in myelodysplastic syndromes and mantle cell lymphoma.
The current approval was based on two randomized, controlled trials evaluating the efficacy and safety of lenalidomide maintenance therapy for the treatment of multiple myeloma patients after autologous stem cell transplant (CALGB 100104 and IFM 2005-02 trials).
These trials demonstrated approximately a 15-month (CALGB) and 18-month (IFM) progression-free survival advantage, at the time of the primary analysis, in patients treated with lenalidomide compared with patients receiving placebo (hazard ratio (HR) in CALGB=0.38; 95% CI: 0.27, 0.54; p<0.001 and HR in IFM=0.50; 95% CI: 0.39, 0.64; p<0.001). The median overall survival was 111 and 106 months for patients treated with lenalidomide compared with 84 and 88 months for patients receiving placebo in the CALGB and IFM trials, respectively. The types, frequency, and severity of adverse events (AEs) observed in the two trials were similar to those previously described in the product label.
Neutropenia, affecting 56% of the 517 patients treated with lenalidomide in both trials, was the most frequently reported grade 3/4 AE. An increased incidence of second primary malignancies was reported among patients treated with lenalidomide compared with those receiving placebo. The lenalidomide product label notes an increase in second primary malignancies in patients with multiple myeloma treated with lenalidomide. The recommended dose and schedule for lenalidomide is 10mg once daily continuously on days 1-28 of repeated 28-day cycles.
Full prescribing information is available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021880s049lbl.pdf
Zykadia receives a Priority Review for frontline use in ALK+ metastatic NSCLC
Novartis said FDA has accepted the company’s supplemental New Drug Application for filing, and granted Priority Review for the expanded use of Zykadia (ceritinib) as a first-line treatment for patients with metastatic non-small cell lung cancer whose tumors are anaplastic lymphoma kinase-positive as detected by an FDA-approved test.
FDA also granted Breakthrough Therapy designation to Zykadia for the first-line treatment of patients with ALK+ metastatic NSCLC with metastases to the brain.
The sNDA submission for first-line use of Zykadia is based on the primary analysis of ASCEND-4, a global phase III, randomized, open-label, multicenter clinical trial which evaluated safety and efficacy of Zykadia compared to platinum-based chemotherapy, including maintenance, in adult patients with Stage IIIB or IV ALK+ NSCLC.
The study was conducted at 134 clinical trial sites across 28 countries, and randomized across 376 patients.
The study found:
Patients treated with first-line Zykadia had a median progression-free survival (PFS) of 16.6 months (95% confidence interval [CI]: 12.6, 27.2), compared to 8.1 months (95% CI: 5.8, 11.1) for patients treated with standard first-line pemetrexed-platinum chemotherapy with pemetrexed maintenance. A 45% risk reduction in PFS was obtained in the Zykadia arm compared to the chemotherapy arm (hazard ratio [HR] = 0.55, [95% CI: 0.42, 0.73; one-sided p value <0.001])1.
In a pre-specified analysis of patients receiving Zykadia without brain metastases at screening, patients experienced a median PFS of 26.3 months (95% CI: 15.4, 27.7), compared with 8.3 months (95% CI: 6.0, 13.7) among patients treated with chemotherapy (HR = 0.48 [95% CI: 0.33, 0.69])1.
In a pre-specified analysis of patients receiving Zykadia with brain metastases at baseline, the median PFS was 10.7 months (95% CI: 8.1, 16.4) in the Zykadia group versus 6.7 months (95% CI: 4.1, 10.6) in the chemotherapy group (HR = 0.70 [95% CI: 0.44, 1.12])1. Intracranial overall response rate (ORR) (72.7%, [95% CI: 49.8, 89.3]) is consistent with whole body ORR (72.5% [95% CI: 65.5, 78.7]). The most common adverse events (AEs) occurring in more than 25% of Zykadia patients were diarrhea (85% vs. 11% with chemotherapy), nausea (69% vs. 55% with chemotherapy), vomiting (66% vs. 36% with chemotherapy), ALT increase (60% vs. 22% with chemotherapy), AST increase (53% vs. 19% with chemotherapy), gamma-glutamyltransferase increase (37% vs. 10% in chemotherapy), decreased appetite (34% vs. 31% with chemotherapy), blood alkaline phosphate increase (29% vs. 5% with chemotherapy) and fatigue (29% vs. 30% with chemotherapy).
FDA accepts Mylan’s BLA for biosimilar pegfilgrastim
Mylan N.V. and Biocon Ltd. said the FDA has accepted Mylan’s Biologics License Application for MYL-1401H, a proposed biosimilar to Neulasta (pegfilgrastim), for filing through the 351(k) pathway.
The proposed biosimilar to Neulasta is used to reduce the duration of neutropenia (low count of neutrophils, a type of white blood cells) and the incidence of fever associated with neutropenia in adult patients treated with chemotherapy in certain types of cancer. The FDA goal date set under the Biosimilar User Fee Act is Oct. 9.
The proposed biosimilar pegfilgrastim is one of the six biologic products co-developed by Mylan and Biocon for the global marketplace.
MIODx licenses immunotherapy technologies from UCSF
MIODx said it has signed an exclusive license for two key immunotherapy technologies from the University of California, San Francisco.
The first technology provides a method to monitor a patient for response to immune checkpoint inhibitor therapy such as PD-L1 and CTLA-4. The second license extends the technology with a method to detect if a patient is likely to have an immune-related adverse event from their immunotherapy regimen.
MIODx also announced that they have entered into an agreement with UCSF to provide immunosequencing services as part of the validation and commercialization of the technology.
MIODx is a privately held company focused on discovery of early detection and prognostic cancer biomarkers through the company’s proprietary platforms. The company’s VerifyDx™ platform utilizes a highly sensitive, multiplex PCR assay and advanced bioinformatics to interrogate multiple DNA and RNA pathways that are implicated in highly metastatic cancer.
In addition to the VerifyDx platform, MIODx utilizes high throughput immune sequencing to generate information on T and B cell diversity that is being applied to monitoring a patient’s response to immunotherapy.