This is GREAT for the sector, no equivocation.
Agreed, but it might take some of the skill out of biotech investing. A big part of biotech investing (at least in my mind) is dissecting public pronouncements by biotechs to try to figure out the extent to which they are spinning.
How good is a potential drug? The closest we get to discovering the "reality" is when we see the briefing material for an FDA AC meeting. Before that, we have only (in order of decreasing spin) company pronouncements, abstracts of presentations and refereed journal articles.
So one of the things I like to do is closely examine company PR releases to see if they are being reasonably straight with us or whether they are trying to put the best face on a poor situation (or are perhaps even deceiving themselves).
In that spirit, I propose what I think will be an instructive exercise for us all. APHT today put out fairly complex PR relating to a trial for gastric cancer. I invite everyone to go ahead and dissect, deconstruct and analyze this release and give the company a mark from 1 (criminally deceptive) through 10 (completely straight and unbiased) on the honesty of the release.
To avoid being influenced by each other (at least in the first pass of this analysis) I suggest that people post their views and analysis of this release at a set time tomorrow - say noon EST. I'll post my initial analysis then too. All are welcome - feel free to contribute even if you are a biotech investment novice.
Feel free to make suggestions and comments about this exercise before the deadline - just don't give away your view on the release itself. One of the great things that SI gives us is the ability to put our collective minds together (so to speak) - but one problem is that I suspect that we tend to get overly swayed by each others' views (cf. the charity portfolios overlap) and so we don't always fully take advantage of multiple viewpoints.
Here's the release:
Press Release Source: Aphton Corporation
Aphton Corporation Reports Positive Final Results in Phase II Trial of G17DT in Combination With Cisplatin and 5-FU in Patients With Advanced Gastric Cancer
Thursday February 5, 8:30 am ET
MIAMI--(BUSINESS WIRE)--Feb. 5, 2004--Aphton Corporation (Nasdaq:APHT - News) today announced final results from its Phase II single-arm clinical trial of G17DT in combination therapy with cisplatin and 5-FU in patients with advanced gastric (stomach) cancer.
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The Phase II trial enrolled a total of 103 chemotherapy-naive patients with advanced gastric cancer from 42 sites in the United States and Europe. Patients received G17DT in combination with cisplatin and 5-FU. G17DT was given at a dose of 500mcg on weeks 1, 5 and 9 with an additional dose at 6 months. Cisplatin was given at a dose of 100mg/m2 during the first day of each 4-week treatment cycle with 5-FU given at a dose of 1000mg/m2/day during the first five days of each 4-week treatment cycle.
The trial included male and female patients over 18 years of age with histologically confirmed adenocarcinoma of the stomach or esophagogastric junction. All patients were chemotherapy naive with measurable metastatic disease and were not suitable for tumor resection with curative intent. All patients must have had a life expectancy of at least 3 months and a Karnofsky index for performance status (KPS), a measure of general health status, of greater than or equal to 70%. Baseline demographic data and health status of patients recruited in the trial were typical of this disease and consistent with published epidemiological studies.
The primary end-point of the trial as specified by the protocol was tumor response by radiographic assessment. Secondary endpoints included evaluation of progression free survival, overall survival, the relationship of immune responsiveness to G17DT and clinical efficacy and safety and tolerability of G17DT in combination with cisplatin and 5-FU. Further analyses investigated the independence of the immune response to G17DT from other clinical parameters. The following results were obtained on the intent to treat population (ITT):
Best overall tumor response rate was 51% (49% partial responders, 2% complete responder) as measured by RECIST criteria. Stable disease was 31% with progressive disease 18%. Confirmed tumor response rate was 28% (partial 27%, complete 1%) with stable disease 48% (ITT).
The one year survival for patients treated with the combination was approximately 19% (ITT).
Median survival for patients treated with the combination was 8.9 months (ITT).
Median progression free survival was 5.3 months (ITT).
Importantly, patients who generated anti-G17 antibodies (N = 79) lived significantly longer than patients who did not generate anti-G17 antibodies (N=24). Analysis of the Kaplan Meier plots showed that G17 responders had a median survival of 10.0 months compared to 3.3 months for G17 non responders (p less than 0.0001, log rank).
A sub-group analysis based on KPS, ranging from 70-100, showed that the survival benefit of G17 responders compared to G17 non-responders remained statistically significant (p less than 0.0001, log rank). At each KPS stratum, G17 responders lived significantly longer than G17 non-responders. This indicates that the survival benefit of G17 responders compared to non-responders was not solely a function of health status.
At each KPS level among the G17 non-responders there were anti-DT antibody responders, indicating that many of the G17 non-responders were immunocompetent, providing a separate indication that survival benefit was not a function of health status.
Baseline laboratory values indicative of health status were similar in both responder and non responder sub-groups providing an additional indication that survival benefit was not a function of health status.
The addition of G17DT did not exacerbate the known systemic toxicity profile of cisplatin and 5-FU.
"Gastric cancer is one of the most devastating and aggressive forms of cancer," said Paul Broome, MD Aphton's VP, European Medical Director. "The results from this trial suggest that G17DT could provide a safe, effective addition to the standard of care, cisplatin and 5-FU, for the significant number of patients worldwide that have this terrible disease. We believe that these data support the addition of G17DT to chemotherapy for the treatment of gastric cancer."
"The data from this trial are quite encouraging for patients who suffer from gastric cancer," stated Jaffer Ajani, M.D., from the MD Anderson Cancer Center. "There is no approved therapy for gastric cancer and current standards of care add only a small clinical benefit at a cost of significant side-effects. The data shown in this trial marks a critical step in adding a safe, targeted biological approach to existing therapies to attack this typically fatal life-threatening disease."
About G17DT
Aphton's anti-gastrin targeted immunotherapy induces in patients antibodies that bind to both gastrin 17 and gly-gastrin 17 and remove them from circulation before they can bind to the cancer cell and initiate cell growth. Gastrin 17 and gly-gastrin 17 are believed to be central growth factors, or the initiating signals, for cell growth, cell proliferation and metastasis, or spread, in pancreatic, gastric (i.e. stomach), esophageal, colorectal and other gastrointestinal (GI) system cancers. This signaling cascade is triggered by gastrin binding to the large numbers of gastrin receptors which appear, de novo, in the great majority of cases, on tumor cell surfaces of the gastrointestinal system. Interrupting this process by immunizing the patient with Aphton's anti-gastrin immunogen is specifically targeted immunotherapy. This specificity of targeting only cancer cells occurs because gastrin is not normally secreted and gastrin receptors are not normally found on cells in the GI system, unless they are malignant, or on the path to malignancy (except for cells involved with normal acid secretion).
Recent findings have shown that inhibiting gastrin inhibits cell growth, proliferation and metastasis, leading to programmed cell death (apoptosis). This tilts the balance from cell growth to cell suicide. Gastrin also stimulates the secretion and expression of other important growth factors and receptors within and on the surfaces of the cancer cells involved in tumor growth. Hence, inhibiting gastrin inhibits all of the foregoing factors that contribute to tumor growth and spread, resulting in tumor cell death. Aphton's anti-gastrin targeted immunotherapy would add a biological dimension to the treatment of gastrointestinal cancers.
About Gastric Cancer
There is only one large, randomized, phase III clinical trial that has been reported in the medical literature with cisplatin plus 5 FU for patients with advanced gastric cancer. In that trial the tumor response rate was 20%, as reported by the European Organization for Research and Treatment of Cancer (EORTC) which conducted the trial. While Aphton's data are not directly comparable to the EORTC study we believe that the results reported by Aphton today do compare favorably with those results.
It is estimated that there are approximately 570,000 patients with gastric cancer in the US, Europe and Japan, alone. The prognosis for the overwhelming majority of these patients is very poor. Patients diagnosed with metastatic disease have five-year survival rates of only about three percent. Surgery and chemotherapy are the primary treatment options currently, but have shown only very limited benefit. Aphton believes that its anti-gastrin targeted immunotherapy approach has the potential to extend patient survival without adding systemic toxicity to the chemotherapy regimen.
Aphton Corporation is a biopharmaceutical company developing products using its innovative targeted immunotherapy technology for neutralizing hormones that participate in gastrointestinal system and reproductive system cancer and non-cancer diseases. Aphton has strategic alliances with Aventis Pasteur for treating gastrointestinal system and other cancers with G17DT in North America and Europe; GlaxoSmithKline for reproductive system cancer and non-cancer diseases worldwide
Peter |
