FDA approved bortezomib (Velcade) injection for previously untreated patients with mantle cell lymphoma.
The approval is based on the results of an international, randomized, head-to-head phase III study that showed that previously untreated patients receiving a bortezomib-containing combination (bortezomib, rituximab [Rituxan], cyclophosphamide, doxorubicin, and prednisone) experienced a 59 percent relative improvement in the study’s primary endpoint of progression-free survival (HR=0.63; p < .001)
The open-label prospective study evaluated 487 patients with previously untreated mantle cell lymphoma who were ineligible or not considered for a bone marrow transplant.
Patients in the bortezomib arm had a median PFS of 25 months, compared to 14 months in patients who received the standard R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) at a median follow-up of 40 months. The complete response rate for patients receiving the bortezomib combination compared to R-CHOP was 44 vs. 34 percent.
Bortezomib was previously approved for the treatment of relapsed or refractory mantle cell lymphoma in 2006.
FDA approved Akynzeo (netupitant and palonosetron) to treat nausea and vomiting in patients undergoing cancer chemotherapy.
Akynzeo is a fixed combination capsule comprised of two drugs. Oral palonosetron, approved in 2008, prevents nausea and vomiting during the acute phase after the start of cancer chemotherapy. Netupitant, a new drug, prevents nausea and vomiting during both the acute phase and delayed phase after the start of cancer chemotherapy.
Akynzeo’s effectiveness was established in two clinical trials of 1,720 participants receiving cancer chemotherapy. Participants were randomly assigned to receive Akynzeo or oral palonosetron. The trials were designed to measure whether the study drugs prevented any vomiting episodes in the acute, delayed and overall phases after the start of cancer chemotherapy.
Results of the first trial showed that 98.5 percent, 90.4 percent and 89.6 percent of Akynzeo-treated participants did not experience any vomiting or require rescue medication for nausea during the acute, delayed and overall phases, respectively.
In contrast, 89.7 percent, 80.1 percent and 76.5 percent of participants treated with oral palonosetron did not experience any vomiting or require rescue medication for nausea during the acute, delayed and overall phases, respectively. The second trial showed similar results.
Akynzeo is distributed and marketed by Eisai Inc. under license from Switzerland-based Helsinn Healthcare S.A.
The European Commission granted marketing approval for Imbruvica (ibrutinib) throughout the European Union, for relapsed or refractory mantle cell lymphoma, or chronic lymphocytic leukemia patients who have received at least one prior therapy, or in first line CLL patients in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemotherapy.
Imbruvica, a first-in-class, oral, once-daily, non-chemotherapy treatment, is being jointly developed and commercialized in the U.S. by Pharmacyclics Inc. and Janssen Biotech Inc., which will market Imbruvica in Europe.
The approval was based on data from a phase II study in MCL, the phase III RESONATE study in CLL and small lymphocytic lymphoma and the phase Ib/II study in CLL/SLL. A worldwide regulatory filing program for ibrutinib currently is underway, according to the drug’s sponsor.
Imbruvica is approved in the U.S. for three indications: for the treatment of patients with MCL and CLL who have received at least one prior therapy, and for the treatment of CLL patients with deletion of the short arm of chromosome 17, including treatment-naive and previously treated del 17p CLL patients.
Pharmacyclics also entered into a master clinical drug supply agreement with Roche to evaluate the safety, tolerability and preliminary efficacy of Imbruvica in combination with Gazyva (obinutuzumab), a CD20-directed antibody that attacks targeted cells both directly and together with the body’s immune system, in patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma.
Initially, a phase III study will be conducted by Pharmacyclics in CLL/SLL. Plans to evaluate the combination for NHL currently are in development. Gazyva is a registered trademark of Genentech Inc.
The study of the investigational combination of Imbruvica and Gazyva through several investigator-sponsored trials also is being considered. Additional details of the agreement were not disclosed.
Janssen Research & Development also submitted a supplemental New Drug Application for Imbruvica to FDA for the treatment of patients with Waldenstrom’s macroglobulinemia. If approved, this will become the fourth indication for Imbruvica, which received an FDA Breakthrough Therapy Designation for WM in February 2013.
The Centers for Medicare and Medicaid Services published two draft local coverage determinations for prostate cancer tests. The drafts were issued through Medicare contractor Palmetto GBA’s MolDx Program.
One a draft LCD, for use of the Decipher Prostate Cancer Classifier test in men who have undergone radical prostatectomy, is the only genomic test for prostate cancer to receive a draft LCD for use in the post-surgery setting. The Decipher test is developed by GenomeDx Biosciences.
Under Medicare policies, a 45-day comment period will commence on Nov. 10. After comments are received and revisions, if any, are made to the draft LCD, the final LCD will be posted within the following 45 calendar days.
MolDX, developed in 2011, facilitates the clinical review, coverage and payment policies for molecular diagnostic tests. The MolDX Program is a contractor to Noridian, a national contractor that administers Medicare benefits for Jurisdiction E, where GenomeDx is located.
According to GenomeDx, Decipher predicts the aggressiveness of a patient’s disease based on genomic information that is distinct from that provided by PSA and other clinical risk factors. Clinical studies have demonstrated that Decipher can accurately predict aggressive disease and help physicians make more informed treatment decisions for men with prostate cancer. Decipher was developed in partnership with the Mayo Clinic.
Palmetto also issued a draft local coverage determination for Prolaris, a prostate cancer test developed by Myriad Genetics Inc.
The determination is posted to the Medicare Coverage Database on the Centers for Medicare & Medicaid Services website, and establishes the coverage policy for Medicare beneficiaries. The current language in the Prolaris draft LCD provides reimbursement coverage for the approximately 50 percent of prostate cancer patients defined as low and very low risk.
FDA granted Orphan Drug Designations for aldoxorubicin in three indications: glioblastoma multiforme, small cell lung cancer and ovarian cancer. Aldoxorubicin, developed by CytRx Corporation, is a modified version of doxorubicin.
If the indications receive approval, the designation provides aldoxorubicin with certain benefits, including seven years of U.S. market exclusivity if the sponsor complies with certain FDA requirements. Additional incentives for the sponsor include tax credits related to qualified clinical trial expenses and a possible exemption from FDA application fees.
Aldoxorubicin is currently being studied in a global phase III clinical trial evaluating aldoxorubicin as a second-line treatment for patients with soft tissue sarcoma. CytRx is also evaluating aldoxorubicin in two phase II clinical trials, one in late-stage GBM and the other in HIV-related Kaposi’s sarcoma. CytRx expects to start a global phase 2b trial in patients with relapsed small cell lung cancer and is undertaking a phase Ib combination study of aldoxorubicin plus gemcitabine as a potential precursor to a trial in relapsed ovarian cancer.
Aldoxorubicin combines doxorubicin with a novel single-molecule linker that binds directly and specifically to circulating albumin. Protein-hungry tumors concentrate albumin, thus increasing the delivery of the linker molecule with the attached doxorubicin to tumor sites. In the acidic environment of the tumor, but not the neutral environment of healthy tissues, doxorubicin is released.
FDA granted priority review to the investigational bispecific T-cell engager antibody construct blinatumomab for the treatment of adults with Philadelphia-negative relapsed/refractory B-precursor acute lymphoblastic leukemia.
Amgen, the drug’s sponsor, also submitted a marketing authorization application to the European Medicines Agency. The submissions include data from a phase II trial of adult patients with Ph- relapsed/refractory B-precursor ALL treated with blinatumomab, which met its primary endpoint.
Blinatumomab, the first of Amgen’s investigational BiTE antibody constructs, has received orphan drug designation from the EMA and FDA, and breakthrough therapy and priority review designation from the FDA for the treatment of ALL.
Blinatumomab is designed to direct T cells against target cells expressing CD19, a protein found on the surface of B-cell derived leukemias and lymphomas. Blinatumomab is also being investigated in pediatric relapsed/refractory ALL, relapsed/refractory Philadelphia positive B-precursor ALL, minimal residual disease positive B-precursor ALL, relapsed/refractory non-Hodgkin’s lymphoma, including relapsed/refractory diffuse large B-cell lymphoma.
