CHICAGO - One of the big problems in cancer therapy is that chemotherapy won't work if patients can't keep enduring it. And often they can't continue to undergo the grueling regimen because of nausea and vomiting, two of the more dismal side effects.
At the American Society of Clinical Oncology meeting here, MGI Pharma Inc. offered more Phase III data regarding palonosetron, its agent designed to prevent those conditions, data that could lead to a market position that would be "transforming" for the company, said President and CEO Lonnie Moulder.
Minneapolis-based MGI, which submitted a new drug application for palonosetron in September, had already reported the drug met its primary and secondary endpoints in a Phase III program of 1,800 patients that included three pivotal trials, but hadn't disclosed how well the drug did against London-based GlaxoSmithKline plc's market leader, Zofran (ondansetron).
It did very well, Moulder said, and the company aims to replace Zofran along with Anzemet (dolasetron mesylate), from Aventis Pharmaceuticals Inc., of Bridgewater, N.J., and Kytril (granisetron), from Nutley, N.J.-based Hoffmann-La Roche Inc.
The Glaxo drug sells twice as much as Anzemet, so "going head to head with Zofran and having these results is significant," he said.
Data were released earlier from Study 99-04, comparing palonosetron and Anzament. At ASCO, numbers from a study known as 99-03 were offered, comparing MGI's drug with Zofran.
The primary clinical endpoint of both studies was complete response, defined as the percentage of patients who did not experience vomiting or use rescue medication during the 24-hour period following chemotherapy.
Trial 99-03 showed that the complete response rate for patients in the 0.25-mg palonosetron arm was significantly greater than the complete response rate among patients who received 32 mg of ondansetron.
During the first 24 hours following chemotherapy (also called the acute phase), 81 percent of the patients treated with a single intravenous 0.25-mg dose of palonosetron achieved a complete response, compared to 68.6 percent of patients treated with 32 mg of ondansetron.
During the delayed phase (days two through five, following chemotherapy), 74.1 percent of patients treated with 0.25-mg palonosetron had a complete response compared to 55.1 percent of patients in the 32-mg ondansetron study arm.
The 5-HT3 antagonists "all have been compared to each other in well-controlled trials in the past, and this is the first time an agent with this mechanism has shown these results," Moulder said.
"Practice today is that a patient will get an intravenous dose of Zofran on day one, or sometimes two doses on day one," he explained. "On follow-up days, on average, patients will get two or three days of oral therapy."
A problem, he said, is that "many of the patients begin breaking through [vomiting] prior to getting that first oral dose. The potential with palonosetron is that there's no need for an oral dose, because of the strong binding affinity and extended plasma half-life of approximately 40 hours."
Importantly, he said, "we're protecting an additional one out of every 10 patients even in the first 24 hours. If you can control nausea and vomiting on day one, you significantly impact even beyond day one and in subsequent cycles of chemotherapy."
The bottom line is that, if patients' vomiting can be delayed, they are more likely to follow through with chemotherapy sessions that may extend their lives significantly - a fact that made MGI's one of the key supportive-care abstracts at ASCO, Moulder said.
For MGI, the bottom line is good, too. The three available drugs chalked up sales of $1.4 billion last year, Moulder told BioWorld Today.
"The cancer indications for those agents is over $800 million but growing at more than 10 percent per year," he said. Other indications are for postoperative nausea and vomiting, for which palonosetron has not been evaluated.
"We have $30 million in revenue now," Moulder said. "We expect to capture at least a 25 percent market share in a market that's growing to at least $1 billion and do it in three or four years, which for MGI would be transforming."
MGI has a "scaled-up sales organization" with a capability "at least equivalent to what the big pharma companies have, and we have clinical differentiation," he said. "Those two combined position us well."
The FDA has a deadline for action on palonosetron this summer, under the Prescription Drug User Fee Act, and MGI will be "market-ready in the second half of the year," Moulder said. Palonosetron was in-licensed from Helsinn Healthcare SA of Lugano, Switzerland, in 2001.
The data from studies 99-03 and 99-04 were pooled for analysis, too. Results showed the complete response rate for patients in the 0.25-mg palonosetron arm was significantly greater than the complete response rate in the pooled ondansetron/dolasetron group during both the acute and delayed phase.
During the acute phase, the complete response rate for palonosetron at 0.25 mg was 72 percent compared to 60.6 percent in the pooled ondansetron/dolasetron group.
For the delayed phase, 64 percent of patients treated with palonosetron 0.25 mg had a complete response compared to 46.8 percent of patients in the ondansetron/dolasetron group.
Moulder said the clinical trial design "for agents [like this] is well established, since other agents have been approved in this area. You give the drug 30 minutes before the chemotherapy and then measure vomiting episodes and rescue medication. That's the complete response."
MGI also offered data showing the efficacy of repeated doses of palonosetron across multiple cycles of chemotherapy, showing the drug continued to work throughout multiple cycles.
The company's stock (NASDAQ:MOGN) closed Monday at $20.70, up 56 cents.