Maurice, I obviously was not clear enough on this. The fact that a particular indication is the apparently best major indication for a drug has almost nothing to do with the choice of the indication on which a company does a clinical trial. In almost every case, once a company decides a drug is worthy of taking to market, it wants to be on the market ASAP, and at the minimal cost to get there. THe label indication at that point is quite secondary, and does not indicate ignorance of who really needs to take this drug. In the case you gave, sure, probably early dosing of early stage lymphoma patients without metastases is the place this drug may end up saving the most lives. But that would be an INSANE one on which to run a clinical trial. Why? Many reasons. First, look at the endpoint. A company has to define, way before the trial begins, the measurable value that it is going to use as the indicator of whether or not the drug worked. This is perhaps the most important factor in selecting the indication that will be taken to Trial #1. (The factors change for subsequent trials.) Why does it matter so much? If you pick a disease for which there is a simple, preferably yes-no (like death, or living at least x weeks), or at least concretely measurable (like did blood chemistry concentration of Y go up or down at least Z %) , you have just made for a shorter, more definitive, and much less expensive trial, because it takes much less time and you get statistically significant results with many fewer patients in your study than if you have a "squishy" endpoint, like the patient "feels better." If your indication involves a set of afflicted patients who are dying, in great pain, becoming terribly disabled, and who have no other good treatment, the FDA is going to make it very easy for you to design and conduct your trial and get it approved FAST. Also, you will not have any problem recruiting patients to be part of your trial, whcih can be a major bottleneck. All of this is reversed if your patient population is doing OK, in early stage whatever, involves children or pregnant women, or where there are alternative therapies that work adequately well. So the fact that Idec chose to do a trial in a patient population who were terminal, failing other therapies, meant that (as grisly as it is to say it), they could use months till death as an endpoint, or at least percent of patients still alive at however months. They were able to select from a host of eager volunteer terminal patients. It was quick and definitive. The FDA did not unduly hold things up. The other group you mentioned wopuld have made for a much slower trial, that might not even have ended up wioth positive results. This way, you can bet that as of now there are lots of patients who have CD20 positive tumors (yes, that is an absolute prerequisite for this drug to have effect), who do not fall within the label indication, who are receiving Ritixan.
As another example of possible interest to IDec is Biogen's clin trial for anti-CD40L. Notice they did initial trials for ITP? Not the big-market indications? (In fact, ITP is not fatal, and is now somewhat adequately treated with a cheap-as-dirt product, prednisone, so Biogen is highly unlikely to make much if any money off this indication.) However, the endpoint is beautifully measurable: put in the drug and see if the platelet count in the patient's blood goes up or down. You might be able to do a trial with 30 patients for a month or two and be ready to file for approval. Same for the second disease that Biogen's CEO just announced they'd be taking to trial this year, namely resistant hemophiliacs, where you just measure whether the patient's level of anti-factor VIII antibodies goes down or not after a shot of anti-CD40L Ab. What's the obvious major market for the drug? LUPUS. Would you want to do a clin trial on a disease known as the "great pretender", where patients inexplicably get worse and better sporadically, and have symptoms that come and go, and no easily measurable and quantifiable endpoint? That makes for a trial that will drain your cash reserves, may take 3-4 years, will need hundreds of patients in the trial, and may come up with equivocal results. In a way, this is the way you would see it whether you were most interested in the company's bottom line, or were interested in getting the drug to market to get it to needy patients ASAP, so it isn't so bad. As soon as Biogen gets that drug approved for either ITP or resistant hemophilia, you can bet that 99.5% of the drug sold is not going into patients with either of those indications, no matter what the label says. Not with the number of interested docs who are publishing dozens of papers a month (take a look at Medline for 1997) on a wide variety of immune-related conditions, including transplant rejection, and just foaming at the mouth waiting for an anti-CD40L mAb to get approved for ANYTHING and available for sale. And Biogen won't have a reimbursement problem either. After the drug is on the market, chances are Biogen will be running a dozen clinical trials to expand the label indications in its own sweet time, the way they are doing for their interferon beta drug. The race is 95 % won with the first to market. ASsuming, of course, the patents work out...
Cheers! |
