MGI Pharma's 5HT3 antagonist, Aloxi (palonosetron), is effective against delayed emesis following the administration of highly emetic chemotherapy

According to the National Cancer Institute over 500,000 Americans received chemotherapy in 2004, and the majority of these patients received an antiemetic such as ondansetron to prevent nausea and vomiting (for an in depth insight into cancer therapeutics including antiemetics see Cancer Market Top 20 Drugs - Supportive Care Grows the Cancer Market). MGI Pharma's 5HT3 antagonist, Aloxi (palonosetron), was launched in 2004 and is attractive because unlike the market leader, GSK's Zofran (Ondansetron), it is effective against delayed emesis.  The study featured here reports for the first time that extended doses of Aloxi are able to limit delayed emesis with highly emetic chemotherapy.

According to the National Cancer Institute over 500,000 Americans received chemotherapy in 2004, and the majority of these patients received an antiemetic such as ondansetron to prevent nausea and vomiting (for an in depth insight into cancer therapeutics including antiemetics see Cancer Market Top 20 Drugs - Supportive Care Grows the Cancer Market).

Chemotherapy typically evokes a biphasic response comprised of nausea during the first 24 hours post-treatment and then a delayed phase peaking a few days later. The severity of nausea and vomiting varies depending on the chemotherapy.  Fluorouracil, Etoposide, low dose Methotrexate and Vinca alkaloids are mildly emetic while Cisplatin, Dacarbazine and high dose Cyclophosphamide are highly emetic.  Doxorubicin, low doses of Cyclophosphamide, Mitoxantrone and Methotrexate are intermediately emetic.  5HT-3 antiemetics have revolutionized the treatment of cancer patients, controlling the initial phase although it should be noted that the delayed phase is relatively resistant to serotonergic drugs.

The 5HT3 antagonist, GSK's Zofran (Ondansetron) is the world's best-selling anti-emetic agent, generating annual US sales worth approximately $1.0 billion in 2003. The product patent expires in June 2006. While this opens the way for generic competition novel formulation with improved efficacy may also compete for this market. For example Hana Bioscience is developing a lingual spray formulation of ondansetron (press release). Alternative novel antiemetics with improved profiles, especially those able to limiy delayed emesis, may also capture the ondansetron market.

One 5HT3 antagonist that has been approved is MGI Pharma's Aloxi (palonosetron), which was launched in 2004.  This agent has an improved pharmacokinetic profile and may therefore provide an extended duration of action. Aloxi is currently approved for the prevention of acute nausea and vomiting associated with moderately and highly emetogenic cancer chemotherapy.  MGI Pharma expect 2004 sales of Aloxi to be in the range of $155 to $160 million while analysts are anticipating peak sales of above $500 million for by 2007.

Aloxi is also the only 5HT3 antagonist approved for the prevention of delayed nausea and vomiting associated with moderately emetogenic cancer chemotherapy; efficacy is significantly greater than ondansetron from about 1 day post chemotherapy.  The featured Ann Oncol paper described an important study demonstrating the efficacy of extended doses of Aloxi in treatment of nausea and vomiting associated with highly emetogenic cancer chemotherapy. 

The recommended dosage of Aloxi is a single bolus administration of 0.25mg (approx 3.75 micrograms/kg). The efficacy of higher doses of Aloxi has been evaluated in a trial of 161 recipients of highly emetogenic cisplatin chemotherapy. The paper in Ann Oncol reports that at 10 and 30 micrograms/kg single doses of Aloxi showed prolonged efficacy in preventing delayed emesis, with approximately one-third of patients who received Aloxi maintaining a complete response throughout the 7-day period following chemotherapy administration.

These data suggest that approval of higher doses of Aloxi could offer a new treatment for delayed emesis produced by highly emetogenic chemotherapy further extending the potential of Aloxi.

Entry date Sunday, March 06, 2005

Ann Oncol. 2004 Feb;15(2):330-7.