FDA Actions & Updates

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

Wednesday, December 6, 2017

The FDA approved trastuzumab-dkst as a biosimilar to trastuzumab for the treatment of patients with breast or metastatic stomach cancer (gastric or gastroesophageal junction adenocarcinoma) whose tumors overexpress the HER2 gene (HER2+). Trastuzumab-dkst is the first biosimilar approved in the U.S. for the treatment of breast cancer or stomach cancer and the second biosimilar approved in the U.S. for the treatment of cancer.

As with any treatment, health care professionals should review the prescribing information in the labeling for detailed information about the approved uses.

"The FDA continues to grow the number of biosimilar approvals, helping to promote competition that can lower health care costs. This is especially important when it comes to diseases like cancer, that have a high cost burden for patients," said FDA Commissioner Scott Gottlieb, MD. "We're committed to taking new policy steps to advance our biosimilar pathway and promote more competition for biological drugs."

The FDA's approval of trastuzumab-dkst is based on review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data that demonstrates trastuzumab-dkst is biosimilar to trastuzumab. It has been approved as a biosimilar, not as an interchangeable product.

Common expected side effects for the treatment of HER2+ breast cancer include headache, diarrhea, nausea, chills, fever, infection, congestive heart failure, insomnia, cough, and rash. Common expected side effects for the treatment of HER2+ metastatic stomach cancer include neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia. Serious expected side effects include worsening of chemotherapy-induced neutropenia.

Like trastuzumab, the labeling for trastuzumab-dkst contains a Boxed Warning to alert health care professionals and patients about increased risks of cardiomyopathy, infusions reactions, pulmonary toxicity, and embryo-fetal toxicity. Patients should stop taking trastuzumab-dkst if cardiomyopathy, anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome occur.


Sunday, November 19, 2017

The FDA has approved obinutuzumab, an engineered monoclonal antibody designed to attach to CD20, in combination with chemotherapy, followed by obinutuzumab alone in those who responded, for people with previously untreated advanced follicular lymphoma (stage II bulky, III, or IV).

The approval is based on results from the phase III GALLIUM study (NCT01332968), which showed superior progression-free survival (PFS) for patients who received this obinutuzumab-based regimen compared with those who received a rituximab-based regimen as an first-line therapy. Follicular lymphoma, the most common indolent form of non-Hodgkin's lymphoma (NHL), is incurable and becomes harder to treat each time it returns.

The obinutuzumab-based regimen significantly reduced the risk of disease worsening or death compared to rituximab by 28 percent (PFS as assessed by independent review committee; HR=0.72; 95% CI 0.56-0.93; p=0.0118). Safety was evaluated based on 1,385 patients with previously untreated follicular lymphoma (86%) or marginal zone lymphoma (14%). The most common grade 3-5 side effects (occurring in at least 5% of patients) observed more frequently in the obinutuzumab arm were low white blood cell count, infusion reactions, low white blood cell count with fever and low platelet count. The most common side effects (occurring in at least 20% of patients) observed at least 2 percent more frequently in the obinutuzumab arm included infusion reactions, low white blood cell count, upper respiratory tract infection, cough, constipation, and diarrhea.

The supplemental Biologics License Application for obinutuzumab, based on the GALLIUM data, was granted Priority Review, a designation given to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease. With this approval, obinutuzumab is available in the U.S. for three different indications across two common types of blood cancer. Other indications for obinutuzumab, include: with the chemotherapy drug, chlorambucil, to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment; with the chemotherapy drug, bendamustine, followed by obinutuzumab alone for follicular lymphoma in adults who did not respond to a rituximab-containing regimen, or whose follicular lymphoma returned after such treatment; and with chemotherapy, followed by obinutuzumab alone in those who responded, to treat stage II bulky, III or IV follicular lymphoma in adults who have not had previous treatment.


Wednesday, November 1, 2017

The FDA has granted accelerated approval to acalabrutinib, a kinase inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

Acalabrutinib is approved under the FDA's accelerated approval pathway, based on overall response rate, which allows for earlier approval of medicines that treat serious conditions and that fill an unmet medical need based on a surrogate endpoint. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. 

"The acalabrutinib approval represents an important development for patients currently battling mantle cell lymphoma, an aggressive type of blood cancer that is typically diagnosed at an advanced stage and associated with a high relapse rate," said Michael L. Wang, MD, Professor, Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, and Principal Investigator of the ACE-LY-004 MCL clinical trial. "In addition to the overall response rate, the high complete response rate of 40 percent seen in this trial illustrates the potential of acalabrutinib to help patients."

The key efficacy results, as assessed by Independent Review Committee, from the ACE-LY-004 trial in 124 adult patients with relapsed or refractory MCL, included overall response rate (80%), complete response (40%), and partial response (40%).

In the trial, the most common adverse reactions (≥20%) of any grade were anemia (46%), thrombocytopenia (44%), headache (39%), neutropenia (36%), diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%). Hematological events were based on laboratory measurements and adverse reactions.

Dosage reductions or discontinuations due to any adverse reaction were reported in 1.6 percent and 6.5 percent of patients, respectively. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8 percent of patients. These data demonstrate the potential impact that acalabrutinib could have on the management of previously-treated MCL.

Meghan Gutierrez, Chief Executive Officer, Lymphoma Research Foundation, said: "Relapse is common in mantle cell lymphoma patients and represents disease progression. When patients learn there is a new treatment option available for their disease, it brings great hope and an opportunity to participate in shared decision making with their healthcare team."​


Thursday, October 26, 2017

The FDA has approved rolapitant IV in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy.

Delayed nausea and vomiting can occur anytime between 25 and 120 hours following chemotherapy, and is often extremely debilitating.

Rolapitant is a highly selective and competitive antagonist of human substance P/neurokinin 1 (NK-1) receptors, which play an important role in the delayed phase of chemotherapy-induced nausea and vomiting (CINV). With a long plasma half-life of approximately 7 days, a single dose of rolapitant, as part of an antiemetic regimen, significantly improved complete response rates in the delayed phase of CINV.

Results from three phase III trials of rolapitant oral tablets demonstrated a significant reduction in episodes of vomiting or use of rescue medication during the 25- to 120-hour period following administration of highly emetogenic and moderately emetogenic chemotherapy regimens. In addition, patients who received rolapitant reported experiencing less nausea that interfered with normal daily life and fewer episodes of vomiting or retching over multiple cycles of chemotherapy. Results from a bioequivalence trial demonstrated comparability of the IV and oral formulations of rolapitant.

Rolapitant IV is supplied in ready-to-use vials and does not require refrigerated storage or mixing. As a result, utilization in busy chemotherapy clinics is straightforward and easily adopted into existing practice patterns for administration of antiemetic regimens associated with emetogenic chemotherapy. The treatment is to be administered up to 2 hours before chemotherapy administration in combination with a 5-HT3 receptor antagonist and dexamethasone. No dosage adjustment is required for dexamethasone, a CYP3A4 substrate, and rolapitant is the first intravenously administered NK-1 receptor antagonist approved by the FDA that does not contain polysorbate 80.

"Many health care providers tend to believe that CINV is no longer an unmet need but the reality is that more than half of patients treated with emetogenic chemotherapy experience delayed CINV, even when prescribed standard preventative therapies, such as a 5-HT3 receptor antagonist and dexamethasone," said Lee Schwartzberg, MD, Professor of Medicine at University of Tennessee Health Science Center. "The FDA approval of [rolapitant] IV gives doctors and nurses a new option to help protect their patients from these often preventable side effects."​


Thursday, October 19, 2017

The FDA has approved axicabtagene ciloleucel, a cell-based gene therapy, to treat adult patients with certain types of large B-cell lymphoma who have not responded to or who have relapsed after at least two other kinds of treatment. A CAR-T cell therapy, axicabtagene ciloleucel, is the second gene therapy approved by the FDA and the first for certain types of non-Hodgkin lymphoma (NHL).

"Today marks another milestone in the development of a whole new scientific paradigm for the treatment of serious diseases. In just several decades, gene therapy has gone from being a promising concept to a practical solution to deadly and largely untreatable forms of cancer," said FDA Commissioner Scott Gottlieb, MD. "This approval demonstrates the continued momentum of this promising new area of medicine and we're committed to supporting and helping expedite the development of these products.

"We will soon release a comprehensive policy to address how we plan to support the development of cell-based regenerative medicine," he continued. "That policy will also clarify how we will apply our expedited programs to breakthrough products that use CAR-T cells and other gene therapies. We remain committed to supporting the efficient development of safe and effective treatments that leverage these new scientific platforms."

Approximately 72,000 new cases of NHL are diagnosed in the U.S. each year, and diffuse large B-cell lymphoma (DLBCL) represents approximately one in three newly diagnosed cases. Axicabtagene ciloleucel is approved for use in adult patients with large B-cell lymphoma after at least two other kinds of treatment failed, including DLBCL, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. The treatment is not indicated for the treatment of patients with primary central nervous system lymphoma.

"The approval of [axicabtagene ciloleucel] brings this innovative class of CAR-T cell therapies to an additional group of cancer patients with few other options – those adults with certain types of lymphoma that have not responded to previous treatments," said Peter Marks, MD, PhD, Director of the FDA's Center for Biologics Evaluation and Research (CBER).

The safety and efficacy of axicabtagene ciloleucel were established in a multicenter clinical trial of more than 100 adults with refractory or relapsed large B-cell lymphoma. The complete remission rate after treatment was 51 percent.

Treatment with axicabtagene ciloleucel has the potential to cause severe side effects. It carries a boxed warning for cytokine release syndrome (CRS) and for neurologic toxicities. Both CRS and neurologic toxicities can be fatal or life-threatening. Other side effects include serious infections, low blood cell counts, and a weakened immune system. Side effects from treatment with axicabtagene ciloleucel usually appear within the first 1-2 weeks, but some side effects may occur later.

Because of the risk of CRS and neurologic toxicities, axicabtagene ciloleucel is being approved with a risk evaluation and mitigation strategy, which includes elements to assure safe use. The FDA is requiring that hospitals and their associated clinics that dispense axicabtagene ciloleucel be specially certified. As part of that certification, staff involved in the prescribing, dispensing, or administering of the therapy are required to be trained to recognize and manage CRS and nervous system toxicities. Also, patients must be informed of the potential serious side effects and of the importance of promptly returning to the treatment site if side effects develop.

To further evaluate the long-term safety, the FDA is also requiring a post-marketing observational study involving patients treated with axicabtagene ciloleucel.

The FDA granted axicabtagene ciloleucel Priority Review and Breakthrough Therapy designations. The treatment also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

​