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

Wednesday, August 23, 2017

The FDA has approved inotuzumab ozogamicin for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

"For adult patients with B-cell ALL whose cancer has not responded to initial treatment or has returned after treatment, life expectancy is typically low," said Richard Pazdur, M.D., Director of the FDA's Oncology Center of Excellence and Acting Director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "These patients have few treatments available and today's approval provides a new, targeted treatment option."

The safety and efficacy of inotuzumab ozogamicin was studied in a randomized trial of 326 patients with relapsed or refractory B-cell ALL who had received one or two prior treatments. Patients were randomized to receive treatment with inotuzumab ozogamicin or an alternative chemotherapy regimen. The trial measured the percentage of patients with complete remission (CR). Of the 218 evaluated patients, 35.8 percent who received inotuzumab ozogamicin experienced CR for a median 8.0 months; of the patients who received alternative chemotherapy, 17.4 percent experienced CR for a median 4.9 months.

Common side effects of inotuzumab ozogamicin include low levels of thrombocytopenia, neutropenia/leukopenia, infection, anemia, fatigue, hemorrhage, pyrexia, nausea, headache, febrile neutropenia, transaminases and/or gamma-glutamyltransferase increased, abdominal pain, and hyperbilirubinemia. Other serious side effects of inotuzumab ozogamicin include myelosuppression, infusion-related reactions and problems with the heart's electrical pulses.

The FDA granted this application Priority Review and Breakthrough Therapy designations. Inotuzumab ozogamicin also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.​


Friday, August 18, 2017

The PARP inhibitor, olaparib has been granted FDA approval for the following:

  • New use of olaparib tablets as a maintenance treatment of adult patients with recurrent, epithelial ovarian, fallopian tube or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy, regardless of BRCA status;
  • New use of olaparib tablets (2 tablets twice daily) as opposed to capsules (8 capsules twice daily);
  • Olaparib tablets are also now indicated for the use in adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCA) advanced ovarian cancer, who have been treated with three or more prior lines of chemotherapy; patients for this indication are selected for therapy based on an FDA-approved companion diagnostic.

Two randomized trials supported the new approvals and the conversion of accelerated approval to full approval, which was originally based on a single-arm trial:

  • SOLO-2 (n=295) confirmed the benefit of olaparib in gBRCA-mutated patients, demonstrating a 70 percent reduced risk of disease progression or death (HR 0.30 [95% CI, 0.22-0.41], P<0.0001) and improved median progression-free survival (PFS) to 19.1 versus 5.5 months for placebo by investigator-assessed analysis.
  • Study 19 (n=265) showed that olaparib reduced the risk of disease progression or death by 65 percent and improved PFS compared with placebo in patients of any BRCA status (HR 0.35 [95% CI, 0.25-0.49], P<0.0001; median PFS of 8.4 months with olaparib vs. 4.8 months with placebo). Additionally, patients in Study 19, treated with olaparib as a maintenance therapy, had a median overall survival of 29.8 months versus 27.8 months for placebo (HR 0.73 [95% CI, 0.55-0.95]).

Richard Penson, MD, Clinical Director of Medical Gynecologic Oncology at Massachusetts General Hospital Cancer Center, Associate Professor of Medicine at Harvard Medical School, and the primary investigator in the SOLO-2 trial, said: "Today's approval demonstrates that olaparib is an effective option for maintenance therapy for certain ovarian cancer patients, regardless of BRCA status. We welcome this news in the ovarian cancer community as more options are important to help us ensure that patients can find a treatment that is right for them." ​


Tuesday, August 15, 2017

The FDA has awarded orphan drug status to DRU-2017-5947 (SurVaxM), an immunotherapy drug, for the treatment for glioblastoma.

Orphan status is a special designation awarded to encourage innovation and exploration of approaches to treat rare diseases that affect relatively few people.

The vaccine stimulates the immune system to kill tumor cells that contain survivin, a protein that helps cancer cells to resist conventional treatments. A phase II study of DRU-2017-5947 given in addition to standard treatment for patients with newly diagnosed glioblastoma is ongoing at Roswell Park Cancer Institute, Buffalo, N.Y., and four other institutions: the Cleveland Clinic, Dana-Farber Cancer Institute, Massachusetts General Hospital, and Beth Israel Deaconess Medical Center.

"We are excited by the results to date and appreciative of this acknowledgement that SurVaxM holds promise," said DRU-2017-5947 co-inventor Robert Fenstermaker, MD, Chair of Neurosurgery at Roswell Park. "Those of us working to help patients with glioblastoma to live longer realize that the gains from existing therapies have been quite limited. We are eager to move this work forward to a larger multicenter randomized study with the momentum provided by the orphan status designation."

The vaccine is designed to control tumor growth and recurrence.

"There are a couple of things that distinguish our approach," added co-inventor Michael Ciesielski, PhD, Assistant Professor of Neurosurgery at Roswell Park. "S[DRU-2017-5947] is an engineered molecule capable of stimulating the immune system in several different ways to recognize and kill cancer cells. And the fact that its target, survivin, is present in many different types of cancer suggests potentially broad application against cancer."

On the strength of an interim analysis of the in-progress phase II study, the investigators expect to pursue late-stage clinical trials with DRU-2017-5947, pending FDA approval. The vaccine is also being studied in other types of cancer, with a separate clinical study underway looking at the drug as part of combination therapy for multiple myeloma.​


Monday, August 7, 2017

The FDA has accepted the supplemental New Drug Application (sNDA) and granted Priority Review for alectinib as a first-line treatment for people with anaplastic lymphoma kinase (ALK)-positive, locally advanced, or metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test. 


This sNDA submission for alectinib is based on results from the phase III ALEX and phase III J-ALEX studies. A Priority Review designation is granted to proposed medicines that, if approved, the FDA has determined to have the potential to provide a significant improvement in the safety or effectiveness of the treatment, prevention, or diagnosis of a serious disease.

Results from the phase III ALEX study and updated results from the phase III J-ALEX study were recently presented at the 2017 ASCO Annual Meeting.

ALEX (NCT02075840/B028984) is a randomized, multicenter, open-label phase III study evaluating the efficacy and safety of alectinib versus crizotinib in treatment-naïve people with ALK-positive NSCLC whose tumors were characterized as ALK-positive by the VENTANA ALK (D5F3) CDx Assay. People were randomized (1:1) to receive either alectinib or crizotinib. The multicenter study was conducted in 303 people across 161 sites in 31 countries.

The J-ALEX study is an open-label, randomized phase III study that compared the efficacy and safety of alectinib with crizotinib in Japanese people. J-ALEX enrolled 207 people with ALK-positive, advanced or recurrent NSCLC who had not been treated with an ALK inhibitor. People were randomized 1:1 to the alectinib group or the crizotinib group.

Alectinib received Breakthrough Therapy Designation from the FDA in September 2016 for the treatment of adults with advanced ALK-positive NSCLC who have not received prior treatment with an ALK inhibitor. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and to help ensure people have access to them through FDA approval as soon as possible. Breakthrough Therapy Designation was granted on the basis of the phase III J-ALEX trial.

Accelerated approval was granted in December 2015 for the treatment of people with ALK-positive metastatic NSCLC who have progressed on or are intolerant to crizotinib. The ALEX study is part of the company's commitment in the U.S. to convert the current accelerated approval of alectinib in people with ALK-positive, metastatic NSCLC who have progressed on or are intolerant to crizotinib to a full approval as an initial treatment. ​


Friday, August 4, 2017

The FDA has expanded the approval of ibrutinib for the treatment of adult patients with chronic graft versus host disease (cGVHD) after failure of one or more treatments. This is the first FDA-approved therapy for the treatment of cGVHD.

 "Patients with cGVHD who do not respond to other forms of therapy—typically corticosteroids to suppress their immune system—now have a treatment option specifically indicated to treat their condition," said Richard Pazdur, MD, Director of the FDA's Oncology Center of Excellence and Acting Director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "This approval highlights how a known treatment for cancer is finding a new use in treating a serious and life-threatening condition that may occur in patients with blood cancer who receive a stem cell transplant."

The efficacy and safety of Imbruvica for the treatment of cGVHD were studied in a single-arm trial of 42 patients with cGVHD whose symptoms persisted despite standard treatment with corticosteroids. Most patients' symptoms included mouth ulcers and skin rashes, and more than 50 percent of patients had two or more organs affected by cGVHD. In the trial, 67 percent of patients experienced improvements in their cGVHD symptoms. In 48 percent of patients in the trial, the improvement of symptoms lasted for up to 5 months or longer.

Common side effects of ibrutinib in patients with cGVHD include fatigue, bruising, diarrhea, thrombocytopenia, muscle spasms, stomatitis, nausea, hemorrhage, anemia and pneumonia.

ibrutinib, a kinase inhibitor, was previously approved for certain indications in treating chronic lymphocytic leukemia, Waldenström's macroglobulinemia and marginal zone lymphoma, as well as under accelerated approval status for mantle cell lymphoma.

The FDA granted this application Priority Review and Breakthrough Therapy designations. Ibrutinib also received Orphan Drug designation for this indication, which provides incentives to assist and encourage the development of drugs for rare diseases.​