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FDA Sets Deadline for Review of Extended-Release Granisetron (Sustol)

Approval decision expected in April

The FDA has informed Heron Therapeutics, Inc., that it expects to conclude its review of the new drug application (NDA) for granisetron (Sustol) injection, extended release, by early April 2016. In February, the FDA had announced that it would not meet the NDA’s Prescription Drug User Fee Act (PDUFA) goal date of January 17, 2016, and would delay taking action until late February 2016.

Granisetron (Sustol) injection, extended release, is a long-acting formulation of granisetron for the prevention of chemotherapy-induced nausea and vomiting (CINV). Granisetron, an FDA-approved 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, was selected by Heron based on its record of safety and efficacy. Extended-release granisetron has been shown to maintain therapeutic drug levels for at least five days with a single subcutaneous injection. The product is being developed for the prevention of both acute (day 1 after the administration of chemotherapy agents) and delayed (days 2 to 5 after the administration of chemotherapy agents) CINV associated with moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC).

Granisetron injection, extended release, was evaluated in the phase 3, placebo-controlled MAGIC (Modified Absorption Granisetron In the Prevention of CINV) trial in patients receiving HEC regimens. This study assessed the efficacy and safety of extended-release granisetron as part of a three-drug regimen with the intravenous (IV) neurokinin-1 receptor antagonist fosaprepitant (Emend, Merck) and the IV/oral corticosteroid dexamethasone. The study’s primary endpoint was achieved. Specifically, the percentage of patients who showed a complete response in the delayed phase was significantly higher in the granistron arm compared with the comparator arm (P = 0.014). Injection-site reactions were the most common adverse events.

Granisetron injection, extended release, was also compared with palonosetron (Aloxi, Eisai) for the prevention of CINV in a phase 3, randomized, observer-blinded, active-controlled, double-dummy, parallel-group trial. Palonosetron is approved for the prevention of acute and delayed CINV associated with MEC regimens and for the prevention of acute CINV associated with HEC regimens. In this pivotal study, which involved more than 1,300 patients, the efficacy of extended-release granisetron was statistically noninferior to that of palonosetron in the prevention of acute and delayed CINV associated with MEC regimens and of acute CINV associated with HEC regimens.

CINV affects 70% to 80% of patients undergoing chemotherapy and has been identified as a leading cause of premature discontinuation of cancer treatment. Although 5-HT3 receptor antagonists are effective treatments for CINV, an unmet medical need exists for patients with CINV during the delayed phase, which occurs on days 2 to 5 after the administration of chemotherapy agents, according to Heron. None of the currently available 5-HT3 receptor antagonists has demonstrated sufficient efficacy to gain FDA approval for the prevention of delayed CINV associated with HEC.

Sources: Heron Therapeutics; March 3, 2016; Heron Therapeutics; February 29, 2016; and Sustol; 2015.

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