FDA Update

August 2014, Vol 4, No 5 - FDA Approvals, News & Updates


Ofatumumab Approved for Chronic Lymphocytic Leukemia

The US Food and Drug Administration approved ofatumumab (Arzerra Injection, GlaxoSmithKline) in combination with chlor­ambucil, for the treatment of previously untreated patients with chronic lymphocytic leukemia, for whom fludarabine-based therapy is considered inappropriate.

The approval was based on the results of a multicenter, randomized, open-label trial comparing ofatumu­mab in combination with chlorambucil with chlorambucil alone. The 447 patients included in the study were deemed ineligible for fludarabine-based therapy because of advanced age or comorbidities. Overall, 72% of patients had ?2 comorbidities, and 48% had a creatinine clearance of <70 mL/min.

Infusion of intravenous ofatumu­mab was administered as 300 mg in cycle 1 on day 1, followed by 1000 mg on day 8 (first arm), or 1000 mg administered on day 1 of all subsequent 28-day cycles (second arm). In both arms, chlorambucil was administered at a dose of 10 mg/m2 orally on days 1 to 7 every 28 days. Before each infusion of ofatumumab, patients received premedication with acetaminophen, an antihistamine, and a glucocorticoid.

The primary end point of the trial was progression-free survival (PFS) as assessed by a blinded independent review committee. The median PFS was 22.4 months (95% confidence interval [CI], 19-25.2) in patients receiving ofatumumab plus chlorambucil compared with 13.1 months (95% CI, 10.6-13.8) in patients receiving chlor­ambucil alone (hazard ratio, 0.57; 95% CI, 0.45-0.72; P <.001).

The most common adverse reactions (?5%) reported with ofatumu­mab plus chlorambucil were infusion reactions, neutropenia, asthenia, headache, leukopenia, herpes simplex, lower respiratory tract infection, arthralgia, and upper abdominal pain. Overall, 67% of the patients who received ofatumu­mab had ?1 symptoms of infusion reaction. In addition, 10% of patients had ­­ a grade ?3 infusion reaction. (April 17, 2014)


Ramucirumab First FDA-Approved Drug for Advanced Stomach Cancer after Chemotherapy

The US Food and Drug Administration (FDA) approved ramucirumab (Cyramza; Eli Lilly) for the treatment of patients with advanced stomach cancer or gastroesophageal junction adenocarcinoma, which mostly affects older adults. Ramucirumab is an angiogenesis inhibitor that blocks the blood supply to tumors and is intended to be used in patients with unresectable cancer or with metastatic stomach cancer after receiving chemotherapy with a fluoropyrimidine- or a platinum-containing agent. This is the first FDA-approved therapy for patients with stomach cancer who have already received chemotherapy.

Ramucirumab was approved under the FDA’s priority review program, and was also granted an orphan drug status, because it is intended to treat rare conditions.

The safety and efficacy of ramucirumab were demonstrated in a clinical trial of 355 patients with unresectable or metastatic stomach or gastroesophageal junction cancer. Patients were randomized to ramucirumab (66%) or to placebo (34%). The main end point was overall survival (OS). The median OS was 5.2 months with ramuciru­mab compared with 3.8 months with placebo (P <.001). Ramucirumab also improved patients’ progression-free survival compared with placebo. A second trial comparing ramucirumab plus paclitaxel versus paclitaxel alone also showed an OS improvement with the addition of ramucirumab.

Common adverse events reported with ramucirumab in clinical trials include diarrhea and high blood pressure. The recommended dose of ramucirumab is 8 mg/kg every 2 weeks, administered over 60 minutes until disease progression or unacceptable toxicity. (April 21, 2014)


Palonosetron Receives New Indication for CINV Prevention in Pediatric Patients

Palonosetron HCl (Aloxi; Eisai) injection received a new US Food and Drug Administration (FDA) indication for the prevention of acute chemotherapy-induced nausea and vomiting (CINV) associated with initial or repeated courses of emetogenic chemotherapy in children aged 1 month to <17 years. This is the first FDA approval of a therapy for the prevention of acute CINV in patients aged 1 month to 6 months. The age of peak cancer incidence among children occurs within the first year of life, so this approval provides an important option to children, and especially infants, undergoing chemotherapy.

The FDA approval was based on 1 randomized, double-blind, noninferiority pivotal trial comparing palonosetron with ondansetron in pediatric patients. The primary end point was complete response, which was achieved in 59.4% of patients using palonosetron compared with 58.6% of patients receiving ondansetron.

The trial also showed that pediatric patients required a higher dose of palonosetron based on weight than that required by adults; however, the safety profile of the drug in pediatric patients was consistent with its safety profile in adults.

Palonosetron HCl is already approved for the prevention of CINV in adults aged ?17 years. (May 28, 2014)