Bill, I do find it strange that British Biotech scientists are now claiming that other companies with effective MMPIs in development will have the same side-effect problems as they are having. How do they know?
Does that make their side effects more acceptable? I would be curious to hear Dr. Millar's thoughts on the subject, the former head of clinical research at British Biotech, who was dismissed in April for supposedly leaking information disputing BBIOY's claims of efficacy of another drug, Zacutex, in trial for pancreatic cancer. European drug regulators did delay approval of Zacutex, pending the results of additional clinical trials. Dr. Millar faxed a letter to the Financial Times on April 29, 1998 which said: "Marimastat is a very interesting drug which must be researched, but it could take a few years or more before we know whether it works on cancer or not. This is totally at odds with the business plan. I presently estimate the chance that maristamat is a useful medicine in cancer at about 40 percent." He considered those prospects good.
So who do you believe???? Dr. Millar, former director of clinical research, responsible for supervising clinical trials or the scientists who remain at BBIOY. Time will tell.
As far as some comments made recently about Agouron's Phase I data for AG3340:
>>I am unable to determine if the latter include 'non advanced' cancer patients? Since AG 3304 is being administered with two established anticancer drugs why would the latter trials be confined to advanced cases?>>
According to the PW release, the patients in Phase I had advanced cancers and had exhausted all other standard cancer treatments, including chemotherapy, radiation and surgery. So "just" stabilization is an improvement over progressive deterioration for these patients, if their lives can be extended with minimal side effects. Agouron never claimed they were aiming to extend survival by 'X" amount of time. As Peter pointed out, they are examining time to progression of disease and the results will be compared to controls not receiving AG3340.
Re:>> why would the latter trials be confined to advanced cases? >>
I don't think anyone condones trying out new unproven drugs on patients with less advanced disease who have not received any therapy. What if there are interactions with the other 'traditional' chemo drugs in the regimen? What if the drug is not effective? The efficacy data has not been reported yet. This information will be revealed later in Phase II/III clinical trials. Agouron's goal IS to use AG3340 in patients with less advanced cancers, as well as in more advanced patients, in combination with other traditional chemotherapy, once efficacy and a side effect profile is established.
Phase I clinical trials determine the maximum safe dosage levels of the drug that does not produce toxicity. Any efficacy results reported from Phase I are of an anecdotal nature. The Phase I results that were reported in the 47 patients with non-small cell lung cancer (NSCLC) used AG3340 alone. Better results have been observed when AG3340 is used in combination with traditional chemotherapy than when either is used alone. Pre-clinical studies in mice examining NSCLC using AG3340 in combination with carboplatin found tumor reductions of up to 65% compared to controls, and a 77% decrease in the formation of new blood vessels.
The results that some here found "unimpressive" in NSCLC used AG3340 as 'monotherapy' and did not report data from all patients.
Bhag, do you have the links or references for the "half a dozen Phase I Cancer drug trial announcements from various companies proclaiming reduction or arrest of growth in tumors and metastasis?"
I'm curious to see what they say.
>Are they all guilty of hype? >More importantly, is Agouron being too conservative.
I get the impression that you think Johnson was too conservative.
You won't find this company hyping their drugs that are still in clinical trials. There was a real backlash against the hype generated by the Entremed article in the New York Times. There have been many drugs that "cured" cancer in animals but did not work in humans. "The field is littered with magic bullets that failed, that were initially hyped as cure-alls, like interleukin-II; monoclonal antibodies in the '70's; and tumor necrosis factor in the 80's." When Dr. Folkman is asked whether he can cure cancer, he invariably replies: "Yes, in mice." Folkman does not think angiostatin and endostatin will be used alone but in combination with other drugs.
I didn't see the CNN interview so who knows what Johnson really said; it's hard to tell from the article. Reports can be clouded by an individual's "perception of events" or by their own agenda, as we have seen. Johnson was cautiously optimistic in his interview on CNBC on May 6 and I don't imagine too much has changed since then. Message 4357298
I guess some of you don't realize you are offending some of us (at least me) when you question the company's ability to make correct decisions. John Metcalf and Peter S. pointed out that it is premature to make conclusions about efficacy from Phase I data and that less advanced patients should respond better than those with more advanced disease. There are other things I would rather do with my time than look for data to dispel some of these unsubstantiated claims. The answers are available on the internet, from the company's press releases or from Investor Relations.
I have confidence in the company and I don't think they would proceed to large scale Phase II/III for AG3340 without good reason, especially after Thymitaq. The World AIDS conference is less than a week away. Surely there are other more pressing issues to discuss.
aids98.ch
We all know protease inhibitors have side effects and that they are not the cure-all for AIDS. That is not new News. Some press releases, especially from from UCSF and Stanford, are focusing only on the negative: the side effects of HAART, lipodystrophy, problems with adherence, resistance, and claiming very high failure rates. There will be seminars and studies at Geneva that deal with lipodystrophy and treatment; immune therapy, vaccines etc. Some seem to have forgotten the New Journal of Medicine article in March that found a 75% decline in the death rate and a 73% decrease in opportunistic infections in HIV patients, attributable to the addition of protease inhibitors to combination therapy.
It is interesting that on the other side of the ocean, focus is on the "radical" improvements in HIV treatment available in developed countries that has allowed HIV to become a treatable disease. This is in contrast to the lack of progress in developing countries where there are 30.6 million people infected with HIV who do not receive treatment. The title and focus of the 12th World Conference on AIDS is "Bridging the Gap." Providing treatment for developing countries is a major problem that needs to be dealt with. Giving small quantities of drugs at low costs is a small start, although UNAIDS says only 3000 patients will be able to afford treatment but many will be able to afford medicine for OI's. There are hopes that a vaccine can be developed that will prevent HIV infection, but that is years off and won't help those already infected.
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