Here's the last of Hambrecht's 1/21 report. Does anybody have Exhibit 3 or better survival data?
EVIDENCE OF EFFICACY IN STELLAR 3
Most Phase III trials have very little data publicly available prior to the release of the primary efficacy analysis. In the case of STELLAR 3, the company has released significant demographic data, enrollment trends, and overall survival curves for the entire patient population.
From the available data, we believe that a large group of patients in the trial is experiencing a prolonged benefit from chemotherapy, resulting in extended survival. The simplest explanation is that these are Xyotax treated patients and the trial is likely to be a success. Extended treatment duration: Previous large trials of NSCLC PS2 patients have demonstrated a median number of chemotherapy doses of approximately two cycles. In STELLAR 3, the median is closer to four cycles of treatment and a significant number of patients (36%) have completed six cycles (Exhibit 2).
EXHIBIT 2: EXTENDED TREATMENT IN STELLAR 3 2004
(as of 5/13/04) N=402
Cycle 1 57 (14%)
Cycle 2 62 (15%)
Cycle 3 30(7%)
Cycle 4 79 (20%)
Cycle 5 31(8%)
Cycle 6 143 (36%)
Source: Company reports
Extended Survival: Previous large trials of NSCLC PS2 patients have demonstrated a median survival of two to five months and one-year survivals of 9-18%. The median and one-year survivals are tracking well ahead of these estimates, according to the company, and a plot of deaths versus patient enrollment (Exhibit 3) demonstrates a tapering off of the death rate indicative of a group of patients with prolonged survival. We believe this is a positive clue that Xyotax may be efficacious.
[Graphical Material Omitted - Call Your Client Service Representative For Availability: Exhibit 3: Slowing Death Rate In Stellar 3]
ALTERNATIVE HYPOTHESES ARE MORE DIFFICULT TO SUBSTANTIATE
There are several other hypotheses which could potentially contribute to better than expected outcomes in the control group: 1. The patient population could include PS 0 and 1 patients. This is highly unlikely. The company has reported that 99% of patients in the trial are documented PS2 patients. 2. The introduction of the EGFR inhibitor, Iressa, may be extending the survival of patients treated in the second-line setting, after failing first-line chemotherapy. This is highly unlikely because new clinical data recently reported by AstraZeneca shows Iressa does not prolong survival in relapsed NSCLC. Cell Therapeutics has reported that only 4% of patients in the trial have received Iressa in the second or third line setting. Other more potentially efficacious agents are also used infrequently-Gemzar (6%) and Taxotere (7%).
3. Patients enrolled at non-Western clinical sites may have different outcomes. Approximately 60% of the patients in STELLAR 3 were enrolled at clinical sites in Eastern Europe and Latin America. The company believes these sites have enrolled PS2 patients according to protocol. The company has also reported that patients enrolled in Eastern Europe and Latin America are not surviving any longer (as a group) than patients in Western Europe or patients in North America, which provides evidence that they demographics of the non-Western patients are unlikely to be meaningfully different.
MORE THAN ONE WAY TO WIN APPROVAL
Any of the three Xyotax Phase III trials is sufficient for approval if a clear survival benefit is demonstrated (p<0.05). We are expecting that STELLAR 3 achieves this outcome and forms the basis for FDA approval as a first-line treatment for NSCLC PS2 patients.
If STELLAR 3 and 4 fall short of demonstrating a statistically significant survival advantage, we believe that a regulatory approval is still likely if a safety benefit is demonstrated. The approval of Eli Lilly’s Alimta for refractory NSCLC is a clear example of the FDA approving a chemotherapy that has not proven superiority, but which has a demonstrated safety advantage.
We believe that if STELLAR 3 and 4 trend towards a positive survival outcome and demonstrate a measurable safety benefit, the FDA will choose to approve Xyotax as a first-line agent in PS2 patients. Clearly, if the STELLAR 3 data is mixed, the regulatory risk will be higher and the eventual market opportunity may be smaller, but it is not a completely binary outcome.
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