Palonosetron Effectively Prevents Emesis and Nausea Induced by High Dose Chemotherapy in Patients Undergoing Autologous Stem Cell Transplantation

BERLIN -

- Single Dose Palonosetron Achieves Optimal Control of Acute Emesis in Patients Receiving Multiday-High Dose Chemotherapy Before Autologous Stem Cell Transplantation.

- The Addition of a Second Dose of Palonosetron After 48 Hours Significantly Reduces the Detrimental Impact of Nausea on Daily Activities in This Setting.

- Data Presented at the ECCO-ESMO Joint European Oncology Conference in Berlin, Germany

New data presented today at the ECCO-ESMO joint European oncology conference in Berlin show that palonosetron, a second generation 5-HT3 receptor antagonist, importantly improves emesis and nausea control in patients undergoing multiday-high dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT). Moreover the addition of a second palonosetron dose 48 hours after the first one significantly reduces the detrimental impact of nausea on daily activities.

The result comes from a spontaneous study conducted by the team coordinated by Dr. Antonio Pinto at Hematology Oncology and Stem Cell Transplantation Unit, National Cancer Institute - IRCCS Fondazione “Sen. G. Pascale”, Naples, Italy.

“The vast majority of patients undergoing multiday-high dose chemotherapy and autologous stem cell transplantation still experience major acute and delayed chemotherapy-induced nausea and vomiting (CINV), showing how emesis control in the ASCT setting remains sub-optimal”, said Dr. Pinto. “Moreover, we know that palonosetron is effective in preventing CINV in patients receiving moderately or highly emetogenic chemotherapy”, he added. “We have previously shown that a single dose of palonosetron effectively prevented CINV, with prevention rates higher than those obtained with the historical 5-HT3 receptor antagonists. The objective of this study was to evaluate whether a subsequent dose of palonosetron may result more effective than a single dose administration in controlling CINV after multiday chemotherapy regimens”, Pinto explained. “And it did, impressively. Despite the emesis control achieved with a single dose, nausea was still experienced by about half of the patients. The administration of the second dose minimized the negative effects of nausea in the delayed phase thus leading to a significant amelioration of patient’s quality of life in the overall period”, he concluded.

60 patients with diagnosis of lymphoma, myeloma, sarcoma, acute leukemia, and breast cancer were accrued. They were all receiving multiday chemotherapy regimens. The first cohort (30 patients) received a single dose of palonosetron (0.25 mg i.v.) plus dexamethasone (8 mg) half an hour before starting HDT; the second cohort (30 patients) received a second dose of palonosetron plus dexamethasone after 48 hours.

The results showed no significant differences between the two groups as to acute CINV evaluation, since 98% of patients achieved a complete response (no emesis, no need for rescue therapy). Only 17 patients (28%) experienced moderate nausea.

Double-dose palonosetron displayed a trend for a better control of delayed nausea, which occurred in 77% of patients versus 53% of those treated with a single dose (p=0.0581). In addition, double palonosetron dosing had a highly significant impact on nausea-related modifications of daily activities as self-assessed by patients at 120 hours from starting of HDT.

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

Palonosetron (palonosetron hydrochloride) is a second generation 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 demonstrates, in clinical trials and clinical practice, a unique long-lasting action in the prevention of CINV. The product has shown to be effective in preventing both acute and delayed CINV in patients receiving Moderately Emetogenic Chemotherapy (MEC). 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*. According to the NCCN (National Comprehensive Cancer Network) Guidelines palonosetron is the preferred 5-HT3 receptor antagonist to be used in a combined regimen with an NK-1 antagonist and dexamethasone to prevent nausea and vomiting induced by Highly Emetogenic Chemotherapy (HEC).

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 greater 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) in more than 40 countries world-wide. 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

* This sentence refer to Moderately Emetogenic Chemotherapy (MEC) setting

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

Contact person at Helsinn Healthcare SA: Paolo Ferrari Head of International Marketing Tel: +41-91-985-21-21. info-hhc@helsinn.com

Source: Helsinn Healthcare SA

Contact person at Helsinn Healthcare SA: Paolo Ferrari, Head of International Marketing, Tel: +41-91-985-21-21, info-hhc at helsinn.com