Palonosetron “Preferred” 5-HT3 Antagonist for Emesis Prevention in Oncology Patients Receiving Highly Emetogenic Chemotherapy

LUGANO, Switzerland - A new release of the NCCN (National Comprehensive Cancer Network) Clinical Practice Guidelines in Oncology on Antiemesis recommends palonosetron as the “preferred” 5-HT3 antagonist in combination with aprepitant and dexamethasone for prevention of emesis in highly emetic risk chemotherapy.

Based on the important multicenter study published in The Lancet Oncology by the equipe of Dr. Mitsue Saito, last February (Saito M., Aogi K., Sekine I. et al.; Lancet Oncology 2009 Feb; 10(2):115-24. Epub 2009 Jan 8), the National Comprehensive Cancer Network (NCCN, a not-for-profit alliance of 21 of the world’s leading cancer centres), antiemesis panel members have reached consensus to include only palonosetron, the second generation 5-HT3 receptor antagonist, as the “preferred” 5-HT3 antagonist, in the combined regimen recommended for emesis prevention in patients undergoing highly emetogenic chemotherapy. According to the NCCN, the newly recommended regimen comprises: palonosetron (0.25 mg IV on day 1) plus aprepitant (125 mg PO on day 1, and 80 mg PO daily on days 2 and 3; on day 1, aprepitant may be substituted by fosaprepitant 115 mg IV) plus dexamethasone (12 mg PO or IV on days 1 to 4).

The decision follows the data recently published by Saito, who showed, in a phase III comparator trial conducted in Japanese patients undergoing highly emetogenic chemotherapy including antracycline and cyclophosphamide containing regimens (AC/EC) that palonosetron is better than granisetron, a first generation drug of the same class, in preventing chemotherapy-induced nausea and vomiting (CINV) during the delayed phase, defined as 24-120 hours after the initiation of anti-cancer treatment. In the acute phase, defined as the first 24 hours of the start of chemotherapy, palonosetron is as effective as granisetron with a comparable safety profile.

“The NCCN recommendation is an important recognition of palonosetron’s therapeutic value and a new milestone achievement for the product”, commented Andrea Meoli, Chief Commercial Officer at Helsinn, the Swiss pharmaceutical group developer and worldwide licensor of palonosetron.

About NCCN (National Comprehensive Cancer Network)

The National Comprehensive Cancer Network, a not-for-profit alliance of 21 of the world’s leading cancer centers, is dedicated to improving the quality and effectiveness of care provided to patients with cancer. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines, including the guidelines on “Antiemesis”, appropriate for use by patients, clinicians, and other health care decision-makers. The primary goal of all NCCN initiatives is to improve the quality, effectiveness, and efficiency of oncology practice so patients can live better lives. For more information about NCCN, please visit the website: www.nccn.org

About Palonosetron (Aloxi(R), Onicit(R), Paloxi(R))

Palonosetron (palonosetron hydrochloride) is a selective 5-HT3 receptor antagonist, developed for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer, with a long half-life of 40 hours and at least 30 times higher receptor binding affinity than currently available compounds. Palonosetron is a second generation 5-HT3 receptor antagonist, and demonstrates, in clinical trials and clinical practice, a unique long-lasting action in the prevention of CINV. Since its availability in USA in September 2003, and since then in more than 40 countries world-wide, there have been over 10 million administrations of palonosetron. The product has shown to be effective in preventing both acute and delayed CINV in patients receiving moderately emetogenic chemotherapies. A single intravenous dose of palonosetron (0.25 mg) provides better protection from CINV than first-generation 5-HT3 receptor antagonists throughout a 5-day post-chemotherapy period*. This means that a single administration of palonosetron also grants protection during the delayed phase of CINV*. Palonosetron 0.075 mg IV is also approved by FDA as a single intravenous dose administered immediately before the induction of anaesthesia for the prevention of postoperative nausea and vomiting (PONV) for up to 24 hours following surgery.

Palonosetron is contraindicated in patients known to have hypersensitivity to the drug or any of its components. The most commonly reported adverse reactions (incidence more than or equal to 2 percent) in CINV trials with palonosetron were headache (9 percent) and constipation (5 percent), and they were similar to the comparators. In PONV trials, the most commonly reported adverse reactions were QT prolongation (5 percent), bradycardia (4 percent), headache (3 percent), and constipation (2 percent), similar to placebo. Palonosetron has been developed by Helsinn Group of Switzerland and today it is marketed as Aloxi(R), Onicit(R), and Paloxi(R). Palonosetron, marketed as Aloxi(R), is the leading brand in the USA within the CINV Day of Chemo segment, and it is steadily growing in the European markets. For more information about palonosetron, please visit the website: www.aloxi.com

About Chemotherapy-induced nausea and vomiting (CINV)

Chemotherapy-induced nausea and vomiting is among the most dreaded side effects following therapy in patients with cancer. Despite prophylaxis, on the day of chemotherapy, up to 30-45 percent of patients experience nausea or vomiting or require rescue therapy following administration of certain types of emetogenic chemotherapy. The 5-HT3 receptor plays a pivotal role in the process of emesis, and agents that antagonise these receptor subtypes are the basis for control of this effect. Following the development of the first generation 5-HT3 receptor antagonists, such as ondansetron and granisetron, in the late ’80s and early ’90s, in recent years new compounds have been made available for preventing CINV, including palonosetron.

About Helsinn Group

Helsinn is a privately owned pharmaceutical group with headquarters in Lugano, Switzerland, and subsidiaries in Ireland and USA. Helsinn is the worldwide licensor of palonosetron. Helsinn’s unique business model is focused on the licensing of pharmaceuticals and medical devices in therapeutic niche areas. The Group in-licenses early stage new chemical entities, completes their development from the performance of pre-clinical/clinical studies and Chemistry, Manufacturing and Control (CMC) development, to the filing for and attainment of their market approval worldwide. Helsinn’s products are sold directly, through the Group subsidiaries, or eventually out-licensed to its network of local marketing and commercial partners, selected for their deep in-market knowledge and know-how, and assisted and supported with a full range of product and scientific management services, including commercial, regulatory, financial, legal and medical marketing advice. The active pharmaceutical ingredients and the finished dosage forms are manufactured at Helsinn’s cGMP facilities in Switzerland and Ireland, and supplied worldwide to its customers. For more information about Helsinn Group, please visit the website: www.helsinn.com

* These sentences refer to Moderately Emetogenic Chemotherapy (MEC) setting

Contact: Paolo Ferrari Head of International Marketing Tel: +41-91-985-21-21 E-Mail: info-hhc@helsinn.com

Source: Helsinn Healthcare SA

Contact: Paolo Ferrari, Head of International Marketing, Tel: +41-91-985-21-21, E-Mail: info-hhc at helsinn.com