FDA Approves AKYNZEO® (netupitant/palonosetron) for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV)

LUGANO, Switzerland and WOODCLIFF LAKE, New Jersey, October 13, 2014 /PRNewswire/ --

-- First New Fixed Combination Targeting Two Critical Pathways Involved in CINV

Helsinn Group and Eisai Inc. announced today that the Food and Drug Administration (FDA) 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 author 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 tumor 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."

About the AKYNZEO® (netupitant/palonosetron) Pivotal Clinical Trials 

The efficacy of AKYNZEO was established in a pivotal, Phase 2, randomized, double-blind, dose-ranging study in 694 patients undergoing cisplatin-based chemotherapy for a variety of tumor 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% versus 80.1%; P=0.032; 98.5% versus 89.7%; P=0.002; 89.6% versus 76.5%; P=0.003, respectively).

The clinical efficacy profile was further established in a multinational, randomized, double-blind, parallel-group, Phase 3 study in 1455 chemotherapy-naïve patients receiving anthracycline and cyclophosphamide-based chemotherapy. Patients were randomized 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% versus 69.5%; P = 0.001), which was also seen in the overall (74.3% versus 66.6%; P = 0.001) and acute (88.4% versus 85.0%; 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.

About AKYNZEO^® (netupitant/palonosetron)  

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 Authorization Application for netupitant/palonosetron fixed combination for the prevention of acute and delayed CINV.

AKYNZEO Important Safety Information 

Warning and Precautions

• Hypersensitivity reactions, including anaphylaxis, have been reported with or without known hypersensitivity to other 5-HT₃ receptor antagonists
• Serotonin syndrome has been reported with 5-HT₃ receptor antagonists alone but particularly with the use of serotonergic drugs. Symptoms associated with serotonin syndrome may include the following combination of signs and symptoms: mental status changes, autonomic instability, neuromuscular symptoms, seizures, and gastrointestinal symptoms. Patients should be monitored for the emergence of serotonin syndrome, and if symptoms occur, discontinue AKYNZEO and initiate supportive treatment

Adverse Reactions

• Most common adverse reactions ( ≥3% and greater than palonosetron): headache, asthenia, dyspepsia, fatigue, constipation and erythema

Drug Interactions

• Use with caution in patients receiving concomitant medications primarily metabolized by CYP3A4. The inhibitory effect on CYP3A4 can last for multiple days
  • Dexamethasone doses should be reduced when given with AKYNZEO
  • Consider the potential effects of increased plasma concentrations of midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) when administering with AKYNZEO
  • Caution and monitoring for chemotherapy-related adverse events are advised in patients receiving chemotherapy agents metabolized primarily by CYP3A4 including docetaxel, paclitaxel, etoposide, irinotecan, cyclophosphamide, ifosfamide, imatinib, vinorelbine, vinblastine, and vincristine
  • Avoid concomitant use of AKYNZEO in patients on chronic use of a strong CYP3A4 inducer such as rifampin as this may decrease the efficacy of AKYNZEO

Use in Specific Populations

• Avoid use of AKYNZEO in patients with severe hepatic impairment, severe renal impairment, or end stage renal disease

AKYNZEO is available by prescription only.

For more information about AKYNZEO, click here for the full Product Information or visit http://www.AKYNZEO.com.

About Helsinn and Eisai 

Helsinn signed a licensing 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 U.S. Inc., the U.S. subsidiary of Helsinn.

About the Helsinn Group 

Helsinn is a family run, privately owned pharmaceutical group focused on building quality cancer care with a large portfolio of products. Founded in 1976 with headquarters in Lugano, Switzerland, Helsinn also has operating subsidiaries in Ireland, the U.S. and a representative office in China. Helsinn's business model is focused on the licensing of pharmaceuticals, medical devices and nutritional supplement products in the therapeutic area of cancer care.

Helsinn Group in-licenses early-to-late stage new chemical entities, completing their development by performing preclinical and clinical studies and associated manufacturing activities. Helsinn then prepares necessary regulatory filings in order to achieve marketing approvals worldwide. Helsinn's products are out-licensed to its global network of marketing and commercial partners that have been selected for their local market knowledge. Helsinn supports these partners by providing a full range of product and scientific management services, including commercial, regulatory, and medical marketing advice. In March 2013, Helsinn established a new commercial organization within its subsidiary, Helsinn Therapeutics (U.S.), Inc., in order to conduct direct sales and marketing activities within the U.S. market. Helsinn's products are manufactured according to the highest quality, safety, and environmental standards at Helsinn's GMP facilities in Switzerland and Ireland from where they are then supplied worldwide to customers. Further information on Helsinn Group is available at http://www.helsinn.com

About Eisai Inc. 

At Eisai Inc., human health care is our goal. We give our first thoughts to patients and their families, and helping to increase the benefits health care provides. As the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd., we have a passionate commitment to patient care that is the driving force behind our efforts to help address unmet medical needs. We are a fully integrated pharmaceutical business with discovery, clinical, manufacturing and marketing capabilities. Our key areas of commercial focus include oncology and specialty care (Alzheimer's disease, epilepsy and metabolic disorders). To learn more about Eisai Inc., please visit us at http://www.eisai.com/US.  

Eisai Inc. has affiliates that are part of a global product creation organization that includes R&D facilities in Massachusetts, New Jersey, North Carolina and Pennsylvania, as well as a global demand chain organization that includes manufacturing facilities in Maryland and North Carolina. Eisai's global areas of R&D focus include neuroscience; oncology; metabolic disorders; vascular, inflammatory and immunological reaction; and antibody-based programs.

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