Helsinn Group Announces First Patient Enrolled in Phase 3b Study of NEPA IV vs NEPA Oral for the prevention of chemotherapy induced nausea and vomiting (CINV) in Women with Breast Cancer

Lugano, Switzerland, March 20, 2018 - Helsinn, a Swiss pharmaceutical group focused on building quality cancer care products, today announced that the first patient has been enrolled in a Phase 3b study to assess the safety and tolerability of IV NEPA fixed combination of fosnetupitant/palonosetron (235 mg/0.25 mg) compared to oral NEPA for the prevention of CINV in women with breast cancer receiving multiple cycles of anthracycline-cyclophosphamide (AC) chemotherapy. This multiregional, Phase 3b study will enroll 400 patients in the US and Europe.

Riccardo Braglia, Helsinn Group Vice Chairman and CEO, said: "We are pleased that NEPA IV is moving into a Phase 3b trial. The purpose of this study is to add important safety information at the disposal of the physicians to potentially assist them to prescribe antiemetics appropriately in patients receiving AC chemotherapy."

The IV formulation of NEPA in highly emetogenic chemotherapy in non-AC patients is currently under FDA evaluation for bioequivalence with oral NEPA, with an anticipated PDUFA date of April 20, 2018. The development program included a repeated dose safety study to further establish the safety of the intravenous formulation and potentially uncover adverse drug reactions that may appear during subsequent clinical practice. The safety profile of IV NEPA was generally similar to that seen with oral NEPA, no anaphylactic and injection site reactions were reported in this study.

Fosnetupitant, a component of NEPA IV was developed without the need for surfactant emulsifier or solubility enhancer to result in a clear injectable solution, thereby reducing the number of excipients and potential related toxicities (Abrantes et al 2016)^[1].

NEPA IV has not been approved for commercial use by any regulatory authority in any part of the world.

About NEPA (netupitant/palonosetron)

In the US:
Akynzeo^® (netupitant 300mg/palonosetron 0.5mg) capsules for oral use was approved in October 2014 in the United States 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 an oral fixed combination of palonosetron and netupitant. Palonosetron, a 5HT3 inhibitor, prevents nausea and vomiting during the acute phase and netupitant, an NK-1 inhibitor, prevents nausea and vomiting during both the acute and delayed phases after cancer chemotherapy.

Important Safety Information about Akynzeo^®

Warnings and Precautions

• Hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving palonosetron 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 concomitant use of serotonergic drugs. Serotonin syndrome can be life threatening. 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. Patients should be informed of the increased risk of serotonin syndrome, especially if Akynzeo^® is used concomitantly with other serotonergic drugs. 

Adverse Reactions

• Most common adverse reactions include headache, asthenia, dyspepsia, fatigue, constipation and erythema 

Drug Interactions

• Use with caution in patients receiving concomitant medications primarily metabolized by CYP3A4. The plasma concentrations of CYP3A4 substrates can increase when co-administered with Akynzeo^®. The inhibitory effect on CYP3A4 can last for multiple days
  • Dexamethasone doses should be reduced when given with Akynzeo^®. A two-fold increase in the systemic exposure of dexamethasone was observed 4 days after single dose of netupitant.
  • Consider the potential effects of increased plasma concentrations of midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) when administering with Akynzeo^®. When administered with netupitant, the systemic exposure to midazolam was significantly increased.
• 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

For additional information please see the US full Prescribing Information for Akynzeo

In the EU:

Akynzeo® (netupitant 300mg/palonosetron 0.5mg) capsules for oral use was approved in May 2015 in the EU. Akynzeo oral is indicated in the EU for adults for the prevention of acute and delayed nausea and vomiting associated with highly emetogenic cisplatin-based cancer chemotherapy and moderately emetogenic cancer chemotherapy.

For additional information please see the EU Summary of Product Characteristics

Oral NEPA has been recommended by various antiemetic guidelines: the National Comprehensive Cancer Network (NCCN) antiemetic guidelines, both in Highly Emetogenic Chemotherapy (HEC; inclusive of AC and carboplatin AUC >=4)) and Moderately Emetogenic Chemotherapy (MEC); the American Society for Clinical Oncology (ASCO) guideline for antiemetics in oncology, in HEC AC and carboplatin (AUC >=4) regimens and the MASCC/ESMO Guidelines in HEC, AC and carboplatin based chemotherapy. Helsinn currently has 20 licensing partners for Akynzeo^® in 167 countries.

About the Helsinn Group

Helsinn is a privately owned pharmaceutical group with an extensive portfolio of marketed cancer care products and a robust drug development pipeline. Since 1976, Helsinn has been improving the everyday lives of patients, guided by core family values of respect, integrity and quality. The Group works across pharmaceuticals, biotechnology, medical devices and nutritional supplements and has expertise in research, development, manufacture and the commercialization of therapeutic and supportive care products for cancer, pain and inflammation and gastroenterology. In 2016, Helsinn created the Helsinn Investment Fund to support early-stage investment opportunities in areas of unmet patient need. The company is headquartered in Lugano, Switzerland, with operating subsidiaries in Switzerland, Ireland, the U.S., Monaco, and China, as well as a product presence in approximately 190 countries globally.

To learn more about Helsinn Group please visit www.helsinn.com

For more information:

Helsinn Group Media Contact

Paola Bonvicini
Group Head of Communication
Lugano, Switzerland
Tel: +41 (0) 91 985 21 21
[email protected]
For more information, please visit www.helsinn.com and follow us on Twitter, LinkedIn and Vimeo.

^[1] J Pharm Sci. 2016 Jul;105(7):2019-26. doi: 10.1016/j.xphs.2016.03.019. Epub 2016 Jun 1. An Overview of Pharmaceutical Excipients: Safe or Not Safe? Abrantes CG¹, Duarte D¹, Reis CP².