FDA approved Zydelig (idelalisib) tablets for the treatment of three B-cell blood cancers.
Zydelig is indicated for patients with relapsed chronic lymphocytic leukemia in combination with rituximab for whom rituximab alone would be considered appropriate therapy; as monotherapy for patients with relapsed follicular B-cell non-Hodgkin lymphoma; and for small lymphocytic lymphoma patients who have received at least two prior systemic therapies.
Accelerated approval was granted for the follicular B-cell and small lymphocytic lymphoma indications based on overall response rate. Zydelig is a first-in-class inhibitor of PI3K delta, a protein that is over-expressed in many B-cell malignancies and plays a role in the viability, proliferation and migration of these cancer cells.
Approval in CLL is supported primarily by data from a randomized, placebo-controlled phase III trial of Zydelig plus rituximab in 220 patients with relapsed CLL who were not able to tolerate standard chemotherapy.
The study was stopped early in October 2013 by an independent data monitoring committee due to a highly statistically significant benefit in progression-free survival in the Zydelig arm as compared to those receiving rituximab alone [HR=0.18 (95% CI: 0.10, 0.32), p<0.0001].
Median PFS was not reached in the Zydelig plus rituximab arm (95% CI: 10.7 months, NR) and was 5.5 months in the placebo plus rituximab arm (95% CI: 3.8, 7.1). FDA granted Zydelig a Breakthrough Therapy designation for relapsed CLL.
Zydelig’s accelerated approval in FL and SLL is supported by data from a single-arm phase II study of Zydelig monotherapy in patients refractory to rituximab and alkylating-agent-containing chemotherapy (FL: n=72; SLL: n=26).
In the study, Zydelig achieved an overall response rate of 54 percent and 58 percent, respectively, in FL and SLL patients. Of the responses seen in FL patients, 8 percent (n=6) were complete responses; all 15 responses in SLL patients were partial responses. The median duration of response was 11.9 months in SLL patients (range: 0.0, 14.7 months) and median duration of response was not reached in FL patients (range: 0.0, 14.8 months). Improvement in patient survival or disease related symptoms has not been established in these indications.
FDA has also approved a risk evaluation and mitigation strategy for Zydelig. The purpose of the Zydelig REMS is to inform healthcare providers of the serious risks of hepatotoxicity, severe diarrhea, colitis, pneumonitis and intestinal perforation. Zydelig is marketed by Gilead Sciences.
FDA approved Imbruvica (ibrutinib) capsules for the treatment of patients with chronic lymphocytic leukemia who have received at least one prior therapy. Imbruvica was also approved for CLL patients with del 17p.
The update to the Imbruvica label is based on data from the phase III RESONATE study, which demonstrated Imbruvica significantly improved progression-free survival and overall survival compared to ofatumumab in patients with previously treated CLL or small lymphocytic leukemia.
Imbruvica is jointly developed and commercialized by Janssen Biotech Inc. and Pharmacyclics Inc.
Imbruvica was initially approved in February 2014 through the FDA’s accelerated approval process, based on data from a phase Ib/2 study for patients with CLL who have received at least one prior therapy. This indication was based on an overall response rate.
In accord with the accelerated approval process, confirmation of clinical benefit in a subsequent phase III trial was required, which has resulted in this updated indication for the use of Imbruvica in patients with CLL who have received at least one prior therapy and in CLL patients with del 17p.
The randomized, international, open-label RESONATE trial enrolled 391 patients with CLL or SLL who had received at least one prior therapy; 32 percent of whom had del 17p.
Patients were administered either 420 mg oral ibrutinib (n=195) once-daily until progression or unacceptable toxicity or intravenous ofatumumab for up to 24 weeks (n=196, initial dose of 300 mg followed by 11 doses at 2,000 mg per dose and schedule consistent with local labeling).
Data showed single-agent, once-daily Imbruvica significantly prolonged PFS (median not reached vs. 8.1 months; HR 0.22, 95% CI, 0.15 to 0.32; P<0.0001) and OS (HR 0.43; 95% CI, 0.24 to 0.79; P=0.05) versus intravenous ofatumumab in previously treated patients with CLL or SLL. The OS results represent a 57 percent statistically significant reduction in the risk of death in patients receiving Imbruvica versus those in the ofatumumab arm.
PFS was the primary endpoint of the RESONATE study, with OS, ORR and safety as key secondary endpoints. Imbruvica was associated with a 78 percent statistically significant reduction in the risk of death or progression versus ofatumumab. ORR was shown to be 42.6 percent in the Imbruvica arm, versus 4.1 percent in the ofatumumab arm.
Data from this study were recently presented during an oral session at the annual meeting of the American Society of Clinical Oncology and simultaneously published online in the New England Journal of Medicine.
FDA granted Priority Review for Avastin plus chemotherapy for the treatment of persistent, recurrent, or metastatic cervical cancer.
The drug’s sponsor, Genentech, submitted a supplemental biologics license application based on data from the phase III GOG-0240 trial. The application has an FDA action date of Oct. 24. Genentech is a member of the Roche Group.
GOG-0240 is an independent, NCI-sponsored study that assessed the efficacy and safety profile of Avastin (bevacizumab) plus chemotherapy (paclitaxel and cisplatin or paclitaxel and topotecan) in women with persistent, recurrent or metastatic cervical cancer.
Data from 452 women showed that the study met its primary endpoint of improving overall survival with a statistically significant 29 percent reduction in the risk of death for women who received Avastin plus chemotherapy compared to those who received chemotherapy alone (median OS: 17.0 vs. 13.3 months; HR=0.71, p=0.004).
Women in the Avastin plus chemotherapy arm also lived longer without disease worsening compared to those who received chemotherapy alone (median PFS: 8.2 vs. 5.9 months; HR=0.67, p=0.002).
There was no increase in treatment-related deaths in the Avastin plus chemotherapy arm as compared to the chemotherapy alone arm.
FDA granted Breakthrough Therapy designationto investigational bispecific T cell engager antibodyblinatumomab,for adults with Philadelphia-negative (Ph-) relapsed/refractory B-precursor acute lymphoblastic leukemia.
The designation was based on the results of a phase II trial of 189 adult patients with Ph- relapsed/refractory B-precursor ALL treated with blinatumomab. Data from the trial were most recently presented at the annual meeting of the American Society of Clinical Oncology and the Congress of the European Hematology Association.
Blinatumomab is an investigational antibody designed to direct the body’s cell-destroying T cells against target cells expressing CD19, a protein found on the surface of B-cell derived leukemias and lymphomas.
Bispecific T cell engager antibodies are a type of immunotherapy using modified antibodies designed to engage two different targets simultaneously, thereby juxtaposing T cells to cancer cells. The antibodies help place the T cells within reach of the targeted cell, with the intent of allowing it to inject toxins and trigger apoptosis.
FDA granted Breakthrough Therapy status to CTL019,an investigational chimeric antigen receptor therapy for the treatment of pediatric and adult patients with relapsed/refractory acute lymphoblastic leukemia.
The filing was submitted by the University of Pennsylvania’s Perelman School of Medicine, which has an exclusive global agreement with Novartis to research, develop and commercialize personalized CAR T cell therapies for the treatment of cancers.
According to the FDA, the designation is intended to expedite the development and review of new medicines that treat serious or life-threatening conditions if the therapy has demonstrated substantial improvement over an available therapy on at least one clinically significant endpoint. The designation includes all of the fast track program features, as well as more intensive FDA guidance.
It is a distinct status from both accelerated approval and priority review, which can also be granted to the same drug if relevant criteria are met.
The European Commission issued marketing authorization approval for Halaven (eribulin)for locally advanced or metastatic breast cancer that has progressed after at least one chemotherapeutic regimen for advanced disease.
Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting, unless patients were not suitable for these treatments.
The authorization for eribulin is based on clinical evidence from two global Phase III trials; EMBRACE and study 301. These studies involved more than 1,800 women.
EMBRACE showed eribulin can prolong median overall survival in heavily pre-treated women with MBC compared to women receiving an alternative treatment of physician’s choice by 2.7 months (13.2 vs 10.5 HR 0.81 (95% CI 0.67, 0.96) nominal p=0.014).
Study 301, a head-to-head trial of eribulin vs. capecitabine, had a co-primary endpoint of overall survival and progression-free survival. The study demonstrated a trend favoring improved overall survival with eribulin compared to capecitabine in the intention-to-treat population, although the improvement was not statistically significant.
Women treated with eribulin had a median overall survival of 15.9 months versus 14.5 months with capecitabine (HR 0.879; 95% CI: 0.770-1.003; p=0.056). For women with human epidermal growth factor receptor 2 negative metastatic breast cancer, overall survival was 15.9 months for eribulin vs. 13.5 months for capecitabine (HR 0.838; 95% CI: 0.715-0.983).
Eribulin is a non-taxane, microtubule dynamics inhibitor.Eribulin belongs to a class of antineoplastic agents, the halichondrins, which are natural products, isolated from the marine sponge Halichondria okadai. It is believed to work by inhibiting the growth phase of microtubule dynamics which prevents cell division.
Mylan Inc. launched Carboplatin Injection, 50 mg/5 ml, in multi-dose vials—the generic version of Bristol-Myers Squibb’s Paraplatin Injection.
Mylan received final approval from FDA for its Abbreviated New Drug Application for this product, which is indicated for the initial treatment of advanced ovarian carcinoma in established combination with other approved chemotherapeutic agents.
Mylan also received final approval for Carboplatin Injection, 150 mg/15 ml, 450 mg/45 ml, 600 mg/60 ml, in multi-dose vials, and intends to launch them subsequently.
FDA approved the Cone Beam Computed Tomography proton therapy solution developed by IBA.
IBA received FDA 510(k) clearance for its imaging platform adaPT Insight, as well as for the Compact Gantry Beam Line. Those combined clearances will enable the CBCT solution to be marketed in IBA’s two Proton Therapy solutions, Proteus PLUS and Proteus ONE, in 2014 and 2015, respectively.
As a component of IBA’s Image Guided Proton Therapy solution, CBCT provides 3D imaging for increased accuracy in patient treatment. IBA’s first CBCT is at the validation phase and the first clinical use is expected for the second half of 2014.
FDA issued a drug safety communication warning that the intravenous chemotherapy drug docetaxel contains ethanol, which may cause patients to experience intoxication or feel drunk during and after treatment. FDA is revising the labels of all docetaxel drug products to warn about this risk.
Docetaxel is a prescription chemotherapy drug used to treat different kinds of cancer, including cancers of the breast, prostate, stomach, head and neck cancers, and non-small-cell lung cancer.
FDA says healthcare professionals should consider the alcohol content of docetaxel when prescribing or administering the drug to patients, particularly in those whom alcohol intake should be avoided or minimized and when using it in conjunction with other medications.
