Aphton Corp.'s stock jumped 16.6 percent on news of positive results from a Phase III trial with G17DT, the monotherapy for pancreatic cancer.
Shares (NASDAQ:APHT) closed Thursday at $7.17, up $1.02. The question now is: Can the company file for - and win - approval on the data?
"I'd give them about a 50/50 chance," said Buddy Lyons, analyst with Stanford Financial Group in Memphis, Tenn., adding that his percentage is somewhat more than others might grant.
"I don't think so," was the answer from Tom Shrader, analyst with Harris Nesbitt Gerard in New York, calling the trial too small.
The trial enrolled 154 treatment-na ve patients with advanced pancreatic cancer from 22 sites in Europe, assigning them randomly to one of two arms; one received G17DT alone, and the other arm received placebo.
"The knock you hear is that they haven't even [tested] it against gemcitabine," the standard of care for pancreatic cancer, Lyons said. "But when they started this trial, the FDA wasn't approving anything, so they said, Let's just compare it with nothing.'"
Another Phase III trial is under way testing G17DT - which contains a portion of the hormone gastrin 17 and diphtheria toxoid, chemically bound together to neutralize G17 and the hormone Gly-G17 - when used with gem citabine vs. gemcitabine alone in advanced pancreatic cancer. Data are expected in mid-2004.
"That's the classic trial, in 400-plus patients," Lyons said. "Am I willing to wait six months for it? You bet. Six months isn't going to get me out of the stock."
Analysis in the G17DT vs. placebo trial was conducted once the protocol-specified 101 deaths were reached.
Enrolled were male and female patients over 18 with histologically or cytologically confirmed pancreatic carcinoma, all patients treatment-na ve with Stage II, III or IV disease and not suitable for tumor resection in an attempt at cure.
Patients had a life expectancy of at least two months and a Karnofsky index for performance status (KPS) of 60 percent. The Karnofsky index, named after the cancer physician who developed it, charts the ability to perform usual activities, evaluates progress after a therapeutic procedure and determines suitability for therapy.
The primary objective of the trial as specified by the protocol was to compare the overall survival between the two arms. Secondary endpoints included comparative analyses of quality of life, time to deterioration of KPS and changes in dry weight. Also analyzed was the relationship of immune responsiveness to G17DT and survival, as well as independence of the immune response to G17DT from other clinical parameters.
In the intent-to-treat population, G17DT, which was safe and well tolerated, yielded a median survival of 151 days, compared with 83 days for patients treated with placebo (p=0.030, log rank). Nine-month survival for patients treated with the drug was about 22 percent, compared to 11 percent for the placebo group.
Kaplan Meier curves, which chart patient progress over time, showed superiority of G17DT over placebo in both Stage IV and Stage II/III subgroups - but in both subgroups the number of patients was too small to reach statistical significance independently.
When combined on an intent-to-treat basis, the survival benefit of G17DT compared to placebo was statistically significant (p=0.030, log rank).
Patients treated with G17DT showed a significantly longer time to deterioration of their Karnofsky scores to 24 weeks, compared to 12 weeks for patients treated with placebo (p=0.044, log rank).
In both treatment groups, mean dry weight tended to decrease during the study, and the decrease from baseline proved consistently less in patients treated with G17DT compared to placebo. What these data mean, though, is hard to say given the small number of patients, Aphton said.
One indicator was clear: Patients who generated anti-G17 antibodies (G17 responders) lived significantly longer than patients who did not generate anti-G17 antibodies (G17 non-responders), or patients who received placebo. Kaplan Meier plots showed that antibody responders to G17 had a median survival of 176 days compared to 63 days for non-responders (hazard ratio=0.44, p=0.0043, log rank) and to 83 days for the placebo group (hazard ratio=0.5, p=0.0028, log rank).
Aiming to show the survival benefit of G17 responders compared to non-responders wasn't caused by their health status, a sub-group analysis based on KPS, ranging from 60-100, showed that the survival benefit of G17 responders compared to G17 non-responders remained statistically significant (p=0.007). At each KPS level, G17 responders lived significantly longer than G17 non-responders.
What's more, at each KPS level among the G17 non-responders there were anti-DT antibody responders, which suggests many of the G17 non-responders were immunocompetent - offering another clue that survival benefit was not because of health status, Aphton said.
The company has a co-promotion and licensing deal for the drug with Lyon, France-based Aventis Pasteur Ltd.
In the conference call Thursday, the company said it's nearing completion of paperwork for filing outside the U.S. first. Aphton will meet with the FDA early next year to discuss its U.S. options regarding the drug. Lacking a positive response, the gemcitabine Phase III is the "fallback" trial, the company said.
"They were going to put [the ex-U.S. filing] on hold when they thought the FDA was loosening up, but I don't think they've lost anything," Lyons told BioWorld Today. "They've just brought the outside-the-U.S. filing up closer than it would have been."
A contract research organization "does most of this work for them," he added. "It depends on how busy they are at any particular time and how much money and manpower they can throw at it."
Shooting for approval on the drug vs. placebo trial first, rather than waiting for the gemcitabine study, is "a logical strategy, if nothing else," Lyons said. "It may not be conventional. We shall see."