Agouron now has a dozen medical sites in place for the pivotal Phase II/III clinical studies of AG3340. They intend to include approximately 50 medical sites and target 500 patients for enrollment in these two studies:
1. One Phase II/III study is to treat advanced non-small lung cancer in combination with paclitaxel and carboplatin. Patients will be compared to a control arm in which patients receive placedbo, pacitaxel and carboplatin.
2. The other Phase II/III is to treat advanced hormone refractory prostate cancer in combination with mitoxantrone and prednisone.
The primary endpoints are time to progression of disease. The secondary endpoints include response rates, survival and quality of life measurements.
Unlike other MMP inhibitors currently under development (British Biotech's Marimastat), AG3340 is highly specific and appears to inhibit only selective types of MMPs, such as the gellatinases, that are believed to be involved in tumor progression.
In preclinical studies, AG3340 exhibited the ability to block blood vessel proliferation necessary for tumor growth (anti-angiogenesis) as well as the ability to block tumor metastasis. AG3340 also enhances the activity of certain chemotherapy drugs.
So far, Phase I human clinical studies of AG3340 in normal healthy volunteers and in cancer patients demonstrated that the product was well tolerated. As a small molecule, AG3340 is easy to administer (pill) and potentially less difficult to manufacture.
James McCammant from the MTSL, a guest on CNBC yesterday who recommended Agouron, also said that Agouron's MMPI does not appear to have the side effects of British Biotech's, i.e. joint pain.
The American Cancer Society estimates there will be 171,500 cases of lung cancer in 1998 and 184,500 new cases of prostate cancer. The five year relative survival rate for all stages of lung cancer is only 14%, while for prostate cancer the survival rate is 89%.
Agouron has pre-clinical studies of AG3340 for macular degeneration, and is presenting some information at an opthamology meeting this week in Florida. It's all pre-clinical still. They hope to begin human clinical studies in the late summer.
Data from the Phase I and Phase I/II clinical studies for AG3340 are expected to be presented at the 10th NCI-EORTC Symposium on New Drugs in Cancer Therapy scheduled for June 16-19 in Amsterdam.
More data on AG3340 Phase I/II will be presented in mid 1998 (H2 98)
Gart inhibitor or AG2034: Phase I dose escalation study ongoing, with pilot clinical studies in certain solid tumors to be initiated later this year.
Clinical results of Phase I dose ranging studies for GART (AG2034) in mid 1998 (H2 98)
Additional clinical data on Viracept will be presented at the World AIDS meeting in Geneva, June 28 to July 3rd.
PW believes that Agouron has a number of product licensing candidates under discussion, primarily to augment its HIV franchise, with a potential announcement in the next 6-12 months (2nd half of 98).
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To change the topic, there were some previous posts, ~4275, 4276, and I'm not sure what the point was. I assume it was "how long it takes to be ready to file an NDA?
>It takes dozens of people months to put together and is the culmination of years of work -- so, yeah, it will take the FDA a while to sort through all that stuff.
>I can verify that...I knew someone that worked for Parke Davis years ago who worked in a huge department that created these reports. Table after table, extremely sophisticated documents in their structure also.
Here are some dates for Viracept, a partial "timeline."
1. Three pivotal Phase II/III clinical trials started in February 1996, in approximately 700 patients
2. In April of 96, Agouron said they hoped to file an NDA for Viracept in the first quarter of 97.
3. Agouron filed the NDA early, in December of 96.
4. March 14th, 1997, the FDA cleared Viracept for marketing, about three months after receiving the NDA.
I'm not implying that AG3340 will proceed as quickly, as the endpoints are very different.
For AG3340 the primary endpoints are time to symptomatic progression of disease. In protease inhibitors the end points are markers for reduced viral load.
The FDA accepts Phase II/III data for accelerated approval.
For AG3340, enrollment needs to be completed and the medical sites arranged. But no one expected Viracept to be approved as quickly either.
Time will tell...but Agouron has shown what it is capable of. As Peter Johnson said in his CNBC interview on May 6t.h. "There are some things that happen in young companies that are kept small and that keep the entrepreneurial spirit that don't necessarily happen elsewhere. A case in point is the very rapid development track that companies like Agouron have been able to execute."
Some quotes by Peter Johnson reported in the Tribune in February 1997, before Viracept approval: "It's been our experience that managing expectations is so important," says
Johnson. "Particularly when you're dealing with diseases where there's a lot of
emotions associated -- with AIDS, with cancer -- the last thing somebody
needs is building unrealistic expectations or building expectations too early."
"It's not appropriate to call drugs like these cures, and there aren't any real
cures on the radar scope," says Johnson. "What Viracept does represent is
one widely used drug in combination therapy, which offers excellent prospects
for patients to manage HIV long term... For many patients who can resume
normal lives it represents not only the lifting of the death sentence that has
been associated with AIDS -- it's kind of a ticket to resume their life."
Johnson's cautious optimism about the progress of the AG3340 trials shown in the recent CNBC interview and when Viracept was approved was more appropriate, imo, than all the hype surrounding the Entremed story, that resulted in extreme disappointment for many cancer patients and their families, who deluged cancer hotlines and physicians offices the following day, with great expectations for a cure for cancer.
Mike McAlary, a columnist who was awarded the Pulitzer Prize for commentary this year for his reporting of the Abner Louima police brutality case in New York City, has colon cancer. In an article published last week, "The Cancer Life, One patient wonders whether he'll beat clock" he described how "we opened the newspaper and there was hope on the front page. ..I couldn't wait to get to my doctor this week. It was all I could do not to beep him on Sunday morning. On Monday.
"So how many people have called you about the cure this morning? I asked (my doctor) pretending to joke about a question I desperately wanted answered."
"Oh angiogenesis is a real thing," Dr. Bernard Kruger said. "It is very encouraging."
Like most patients, I steeled myself against bad news before asking the overwhelming question: How soon? "Maybe four or five years away"
"Can I make it that long? It is the question being asked in every ward, beneath every IV pole this week as cancer people measure out their lives, one drip at a time."
Further on in the article, .
"I have to laugh sometimes when I think about it. Who would have thought two years ago that a person would rather have AIDS than cancer? But there is more hope for living with
HIV than my colon cancer." |
