FDA Actions & Updates
The latest approvals, designations, and new indications from the U.S. Food and Drug Administration for oncology drugs.

Wednesday, March 29, 2017

The FDA approved niraparib for the maintenance treatment (intended to delay cancer growth) of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer whose tumors have completely or partially shrunk (complete or partial response, respectively) in response to platinum-based chemotherapy.

"Maintenance therapy is an important part of a cancer treatment regimen for patients who have responded positively to a primary treatment," said Richard Pazdur, MD, acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research and director of the FDA's Oncology Center of Excellence. "[Niraparib] offers patients a new treatment option that may help delay the future growth of these cancers, regardless of whether they have a specific genetic mutation."

Niraparib is a poly ADP-ribose polymerase (PARP) inhibitor that blocks an enzyme involved in repairing damaged DNA. By blocking this enzyme, DNA inside the cancerous cells may be less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of tumor growth.

 The safety and efficacy of niraparib were studied in a randomized trial of 553 patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received at least two prior treatments of platinum-based chemotherapy and who had experienced a complete or partial response to their most recent chemotherapy treatment. Patients were tested with an FDA-approved test to determine whether they had a specific gene mutation, called a deleterious or germline BRCA mutation. The trial measured the length of time the patients' tumors did not grow after treatment (progression-free survival) in patients with and without the mutation. The median progression-free survival for patients taking niraparib who had a germline BRCA mutation was 21 months compared to 5.5 months for the same patient population taking a placebo. The median progression-free survival for patients taking niraparib who did not have a germline BRCA mutation was 9.3 months compared to 3.9 months for the same patient population taking a placebo.

 Common side effects of niraparib include anemia, thrombocytopenia, neutropenia or leukopenia, heart palpitations, nausea, constipation, vomiting, distention, mucositis, diarrhea, dyspepsia, dry mouth, fatigue, decreased appetite, urinary tract infection, AST/ALT elevation, myalgia, back pain, arthralgia, headache, dizziness, dysgeusia, insomnia, anxiety, nasopharyngitis, dyspnea, cough, rash, and high blood pressure (hypertension). Niraparib is associated with serious risks, such as hypertension, hypertensive crisis, myelodysplastic syndrome, acute myeloid leukemia, and bone marrow suppression.Women who are pregnant or breastfeeding should not take niraparib because it may cause harm to a developing fetus or a newborn baby.

 The FDA granted this application Fast Track, Priority Review and Breakthrough Therapy designations.

 Niraparib also received Orphan Drug designation specifically for its use in treating recurrent epithelial ovarian cancer. This designation provides incentives to assist and encourage the development of drugs for rare diseases.


Tuesday, March 28, 2017

The FDA has accepted a New Drug Application (NDA) for olaparib tablets (300mg twice daily) for use in platinum-sensitive, relapsed ovarian cancer patients in the maintenance setting. The FDA has also granted priority review status with a Prescription Drug User Fee Act set for third quarter 2017. The NDA submission includes the phase III SOLO-2 trial data, which showed a reduced risk of disease progression by 70 percent, compared with placebo in germline BRCA-mutated patients. SOLO-2 trial results were presented on at the 2017 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.

Results from the phase III SOLO-2 trial demonstrated a significant improvement in progression-free survival (PFS) with olaparib tablets, compared with placebo. The trial met its primary endpoint of investigator-assessed PFS (HR 0.30; 95% CI 0.22-0.41; P<0.0001; median 19.1 months vs. 5.5 months).


PFS as measured by Blinded Independent Central Review (BICR) evaluation, a pre-specified sensitivity analysis supporting the primary endpoint, demonstrated a median PFS of 30.2 months vs 5.5 months for placebo, representing an improvement of 24.7 months (HR 0.25; 95% CI 0.18-0.35; P<0.0001).1

The safety profile for patients treated with olaparib tablets during the SOLO-2 trial was generally consistent to those observed with the currently approved capsule formulation. Grade ≥3 adverse events were reported in 36.9 percent of patients treated with olaparib, and in 18.2 percent of patients who received placebo.

Olaparib tablets are an investigational formulation and are not FDA-approved for any use at this time. Olaparib capsules (400mg twice daily) are currently approved in the U.S. as a monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated (as detected by an FDA-approved test) advanced ovarian cancer, who have been treated with three or more prior lines of chemotherapy. The indication is approved under accelerated approval, based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.


Monday, March 27, 2017

The FDA has granted Fast Track designation to CMD-003 for patients with relapsed/refractory lymphoma and post-transplant lymphoproliferative disease associated with the oncogenic Epstein-Barr virus (EBV).

CMD-003, also known as baltaleucel-T, is an investigational therapy in which the patient's T cells are activated to kill malignant cells expressing EBV antigens. It has the potential to address a range of EBV-associated lymphomas, nasopharyngeal carcinoma, and gastric cancer.

CMD-003 is currently being investigated in the international, open label phase II CITADEL clinical trial for patients with extranodal natural killer T-cell lymphoma, a type of non-Hodgkin lymphoma. A phase II CIVIC clinical trial has also been opened to explore the potential benefits of CMD-003 for patients with EBV-associated diffuse large B-cell lymphoma, Hodgkin lymphoma, and post-transplant lymphoproliferative disease.

The FDA's Fast Track is a process designed to facilitate the development and to expedite the review of drugs to treat serious conditions and fill an unmet medical need. The FDA will take appropriate actions to advance the development and review of the application for approval of such a product. FDA Fast Track status also allows for more frequent interactions with the FDA review team and a rolling

Biologics License Application for earlier review.


Monday, March 27, 2017

The FDA has granted Priority Review for the expanded use of ceritinib as a first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. The FDA also granted Breakthrough Therapy designation to ceritinib for the first-line treatment of patients with ALK+ metastatic NSCLC with metastases to the brain.

The sNDA submission for first-line use of ceritinib is based on the primary analysis of ASCEND-4, a global phase III, randomized, open-label, multicenter clinical trial that evaluated safety and efficacy of ceritinib 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 the following:

  • Patients treated with first-line ceritinib 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 percent risk reduction in PFS was obtained in the ceritinib arm compared to the chemotherapy arm (hazard ratio [HR] = 0.55, [95% CI: 0.42, 0.73; one sided p value <0.001]).
  • In a pre-specified analysis of patients receiving ceritinib 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]).
  • In a pre-specified analysis of patients receiving ceritinib with brain metastases at baseline, the median PFS was 10.7 months (95% CI: 8.1, 16.4) in the ceritinib group versus 6.7 months (95% CI: 4.1, 10.6) in the chemotherapy group (HR = 0.70 [95% CI: 0.44, 1.12]). 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 occurring in more than 25 percent of ceritinib 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-glutamyl transferase 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).


Wednesday, March 15, 2017

The FDA has approved ribociclib, formerly known as LEE011, in combination with an aromatase inhibitor as initial endocrine-based therapy for treatment of postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer.


Ribociclib is a CDK4/6 inhibitor approved based on a first-line phase III trial that met its primary endpoint early, demonstrating statistically significant improvement in progression-free survival (PFS) compared to letrozole alone at the first pre-planned interim analysis. Ribociclib was reviewed and approved under the FDA Breakthrough Therapy designation and Priority Review programs. The FDA approval is based on the superior efficacy and demonstrated safety of ribociclib plus letrozole versus letrozole alone in the pivotal Phase III MONALEESA-2 trial. The trial, which enrolled 668 postmenopausal women with HR+/HER2- advanced or metastatic breast cancer who received no prior systemic therapy for their advanced breast cancer, showed that ribociclib plus an aromatase inhibitor, letrozole, reduced the risk of progression or death by 44 percent over letrozole alone (median PFS not reached (95% CI: 19.3 months-not reached) versus 14.7 months (95% CI: 13.0-16.5 months); HR=0.556 (95% CI: 0.429-0.720); p<0.0001)


More than half of patients taking ribociclib plus letrozole remained alive and progression free at the time of interim analysis, therefore median PFS could not be determined. At a subsequent analysis with additional 11-month follow-up and progression events, a median PFS of 25.3 months for ribociclib plus letrozole and 16.0 months for letrozole alone was observed. Overall survival data is not yet mature and will be available at a later date.


"In the MONALEESA-2 trial, ribociclib plus letrozole reduced the risk of disease progression or death by 44 percent over letrozole alone, and more than half of patients (53%) with measurable disease taking ribociclib plus letrozole experienced a tumor burden reduction of at least 30 percent. This is a significant result for women with this serious form of breast cancer," said Gabriel N. Hortobagyi, MD, Professor of Medicine, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center and MONALEESA-2 Principal Investigator. "These results affirm that combination therapy with a CDK4/6 inhibitor like ribociclib and an aromatase inhibitor should be a new standard of care for initial treatment of HR+ advanced breast cancer."