The US Food and Drug Administration (FDA) has accepted for review biotechnology company Heron Therapeutics Inc’s New Drug Application (NDA) resubmission for Sustol (granisetron) injection, extended release, for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) associated with moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) regimens.
The FDA has assigned a Prescription Drug User Fee Act (PDUFA) goal date of January 17, 2016.
The NDA filing includes data from the MAGIC study, Heron’s recently completed, multi-center, placebo-controlled, phase 3 study of Sustol for the prevention of delayed CINV in more than 900 patients receiving HEC regimens. Data from an earlier phase 3 study of more than 1,300 patients, which were previously submitted to the FDA, demonstrated Sustol’s efficacy in the prevention of acute and delayed CINV associated with MEC regimens and acute CINV associated with HEC regimens.
“We believe that the MAGIC study has demonstrated Sustol’s superior ability to improve the lives of patients suffering from the debilitating effects of nausea and vomiting associated with chemotherapy compared to the current standard-of-care,” commented Barry D. Quart, Pharm.D., chief executive officer of Heron.
“We look forward to working closely with the FDA during the review of the Sustol NDA and moving forward with commercial planning in anticipation of Sustol’s potential launch early next year.”
Sustol injection, extended release, which utilises Heron’s proprietary Biochronomer drug delivery technology, is Heron’s novel, long-acting formulation of granisetron for the prevention of CINV. Granisetron, an FDA-approved 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist was selected due to its broad use by physicians based on a well-established record of safety and efficacy. Sustol has been shown to maintain therapeutic drug levels of granisetron for five days with a single subcutaneous injection. Sustol is being developed for the prevention of both acute (day 1 following the administration of chemotherapy agents) and delayed (days 2-5 following the administration of chemotherapy agents) CINV associated with MEC or HEC. While other 5-HT3 antagonists are approved for the prevention of CINV, Sustol is the first agent in the class to demonstrate efficacy in reducing the incidence of delayed CINV in patients receiving HEC, a major unmet medical need, in a randomized phase 3 study.
Affecting 70-80 per cent of patients undergoing chemotherapy, CINV is one of the most debilitating side effects of such treatments, often attributed as a leading cause of premature discontinuation of cancer treatment. 5-HT3 receptor antagonists have been shown to be among the most effective and preferred treatments for CINV. However, an unmet medical need exists for patients suffering from CINV during the delayed phase, which occurs on days 2-5 following the administration of chemotherapy agents. Only one 5-HT3 receptor antagonist is approved for the prevention of delayed CINV associated with MEC, and no 5-HT3 receptor antagonists are approved for prevention of delayed CINV associated with HEC.
Sustol was the subject of a recently completed, multi-center, placebo-controlled, phase 3 clinical study in patients receiving HEC regimens known as MAGIC. The MAGIC study evaluated the efficacy and safety of Sustol as part of a three-drug regimen with the intravenous (IV) neurokinin-1 (NK1) receptor antagonist fosaprepitant and the corticosteroid dexamethasone. The MAGIC study, which was conducted entirely in the US using the 2011 ASCO guidelines for classification of emetogenic potential, is the only phase 3 CINV prophylaxis study in a HEC population performed to date to use the currently recommended, standard-of-care, three-drug regimen as a comparator: a 5-HT3 receptor antagonist, fosaprepitant, and dexamethasone. The study's primary endpoint was achieved. Specifically, the percentage of patients who achieved a complete response in the delayed phase was significantly higher in the Sustol arm compared with the comparator arm (p=0.014). Adverse events reported in the study were generally mild to moderate in severity and of short duration, with the most common being injection site reactions (ISRs). In July 2015, Heron resubmitted its NDA for Sustol to the US FDA, and the FDA has assigned a Prescription Drug User Fee Act goal date of January 17, 2016. Sustol is not approved by the FDA or any other regulatory authority.