The US Food and Drug Administration (FDA) has approved Akynzeo for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. Akynzeo is the first approved fixed combination oral agent that targets two critical signaling pathways associated with CINV by combining netupitant, an NK1 receptor antagonist, and palonosetron, a 5-HT3 receptor antagonist, in a single capsule for the prevention of CINV.

"Patients receiving chemotherapy face a significant burden due to CINV. Akynzeo may help alleviate part of that burden of chemotherapy by better managing nausea and vomiting up to five days following chemotherapy," said Paul J. Hesketh, M.D., Akynzeo pivotal study lead authour and chair, Lahey Health Cancer Institute and director of Thoracic Oncology, Lahey Hospital & Medical Center. "The results from the pivotal trials show that Akynzeo provides superior prevention against nausea and vomiting compared with oral palonosetron. As a result, physicians may be able to help patients manage CINV with a treatment that works both at the time of chemotherapy administration, and up to five days following treatment."

The approval of Akynzeo was based on the submission of phase 2 and phase 3 trials with Akynzeo in patients undergoing treatment with moderately and highly emetogenic chemotherapy regimens for a variety of tumour types. The most common adverse reactions reported with Akynzeo were headache, asthenia, fatigue, dyspepsia, constipation and erythema.

CINV is one of the most common side effects of chemotherapy. Its management has been refined over the past several decades, but despite the existence of effective treatments and clear antiemetic guidelines, many patients still suffer from CINV, particularly during the delayed phase after chemotherapy. Studies show that patients often receive antiemetic drug regimens that are inconsistent with CINV treatment guidelines, which call for multiple-pathway targeted antiemetic prophylaxis. Akynzeo provides cancer care teams with two antiemetics in a single oral fixed combination capsule. A combination of an NK1 receptor antagonist, a 5-HT3 receptor antagonist and dexamethasone meets guideline recommendations for optimal antiemetic therapy following highly emetogenic chemotherapy.

"Helsinn is delighted with the FDA approval of Akynzeo and we look forward to a successful launch in the United States. We are proud of our long-standing partnership with Eisai and Akynzeo is the newest development in our combined efforts," said Riccardo Braglia, Helsinn's group chief executive officer. "This approval offers patients access to a new treatment option for CINV prevention that is effective in preventing both nausea and vomiting, particularly in the delayed phase, following emetogenic chemotherapy regimens."

"The approval of Akynzeo represents an important development in the prevention of acute and delayed nausea and vomiting for patients," said Yuji Matsue, chairman and chief executive officer, Eisai Inc. "We are proud to achieve this milestone with Akynzeo as we work to further our human health care mission to provide patients going through what we know can be emotionally- and physically-demanding cancer treatment with an additional option for CINV prevention."
The efficacy of Akynzeo was established in a pivotal, phase 2, randomised, double-blind, dose-ranging study in 694 patients undergoing cisplatin-based chemotherapy for a variety of tumour types. The efficacy of Akynzeo was assessed in 135 chemotherapy-naïve patients who received Akynzeo (netupitant 300 mg/palonosetron 0.5 mg), and 136 patients who received oral palonosetron 0.5 mg. For the key efficacy endpoints of complete response (CR), defined as no emetic episode and no use of rescue medication, for the delayed phase (25-120 hour interval), the acute phase (0-24 hour interval), and the overall phase (0-120 hours) after the start of chemotherapy administration, Akynzeo showed significantly higher complete response rates compared with oral palonosetron in all phases (90.4 per cent versus 80.1 per cent; P=0.032; 98.5 per cent versus 89.7 per cent; P=0.002; 89.6 per cent versus 76.5 per cent; P=0.003, respectively).

The clinical efficacy profile was further established in a multinational, randomised, double-blind, parallel-group, phase 3 study in 1455 chemotherapy-naïve patients receiving anthracycline and cyclophosphamide-based chemotherapy. Patients were randomised to receive a single oral dose of either Akynzeo plus dexamethasone or palonosetron plus dexamethasone prior to chemotherapy. The percentage of patients who met the primary endpoint of CR in the delayed phase was significantly higher in the Akynzeo group compared to the oral palonosetron group (76.9 per cent versus 69.5 per cent; P = 0.001), which was also seen in the overall (74.3 per cent versus 66.6 per cent; P = 0.001) and acute (88.4 per cent versus 85.0 per cent; P = 0.047) phases post chemotherapy. In this study, Akynzeo was generally well tolerated with a safety profile similar to that of palonosetron.

In a separate study, 309 patients undergoing initial and repeat cycles of chemotherapy (including carboplatin, cisplatin, oxaliplatin, and doxorubicin regimens) received Akynzeo; efficacy was maintained throughout all cycles.

Akynzeo is an oral, fixed combination of an NK1 receptor antagonist, netupitant, and a 5-HT3 receptor antagonist, palonosetron, that targets two critical signaling pathways associated with chemotherapy-induced nausea and vomiting (CINV).

Additional regulatory submissions for netupitant/palonosetron fixed combination are underway worldwide. On January 22, 2014, the European Medicines Agency (EMA) started to review the submission of Helsinn's Marketing Authorisation Application for netupitant/palonosetron fixed combination for the prevention of acute and delayed CINV.

Helsinn signed a licencing agreement with Eisai Inc. granting Eisai commercial rights for Akynzeo in the United States.  Under the terms of the agreement, Helsinn is responsible for conducting all development activities (Chemistry and Manufacturing Controls [CMC], preclinical and clinical), obtaining regulatory approvals and holding the New Drug Application (NDA). Akynzeo will be co-promoted in the United States by Eisai Inc. and Helsinn Therapeutics US Inc., the US subsidiary of Helsinn.