Thursday, October 05, 2006

Avastin and Lucentis -as I understand it..

This morning I thought of writing a nice post on a significant piece in the news, about Lucentis and Avastin, both protein pharmaceuticals marketed by Genentech. The news/debate is significant to me for personal as well as professional reasons. So here's a write up of what I get from it.

( Of course, none of this is new information not available from online sources and NEJM except I think for the last para, so for a full understanding of your own, I suggest you read the references posted below)

The drugs in the news are antibodies made by Genentech. Lucentis was approved on June 30 2006 for choroidal neovascularization in age-related macular degenration. It is a great drug, but the catch is that it costs approx $2k for one injection, which has to be taken monthly. Many doctors are using another drug Avastin, also made by Genentech which essentially works in the same way as Lucentis, but is FDA approved for colon cancer. This injection however, costs only $17-$80 ( though sometimes it could costs the patient about $350 to get it). Considering the gigantic difference in costs, without an immediate apparent benefit of Lucentis/liability of Avastin, doctors seem to prefer administering Avastin.

Of course, in theory this is not without problems. Before any FDA approved drug comes into the market, it undergoes extensive clinical trials for treating that disease, including toxicity and tolerability studies, up to efficacy and safety. While Genentech did these studies for Lucentis, it hasn't undertaken them for Avastin(for macular degen). And since it already has Lucentis on the market for wet-MD, it is reluctant/ not interested in conducting such trials for Avastin. Their logic: why undertake a huge study for something which hasn't really been proven to be significantly better when another drug already exists and has just recently been approved. (now if Lucentis was a competitor's drug, they would not have cared ONE bit about the costs, and gone ahead anyway, but since both drugs belong to the same company, this becomes a unique case.)

It also claims, and somewhat justifiably that since the preparation for Avastin has not been formulated specifically for ocular use, it does not undergo the more stringent tests an intraocular preparation would undergo. ( Though I don't know if the tests for IV adminstration would allow for less stringent criteria). The sterility of the preparation might be compromised by the doctor making aliquots of the larger dose of Avastin into the smaller doses needed for intra-ocular administration. ( well, thats what hospital pharmacies, pharmacists and sterile hoods are for). Also, while Lucentis are just antibody fragments, Avastin is the entire antibody, which basically will have different effects (either beneficial or toxic) than Lucentis.

Now yet, doctors seem to be fond of it, and continue using it. And one cannot ignore the cost issue. Of course, Genentech won't do a full scale clinical trial, as long as it believes that Lucentis works just fine.( In fact they believe it's better) So who does this study comparing the two? And who picks the tab? Well, right now, grant has been submitted to the National Eye Institute for comparing the two head-to-head in the clinic. If this comes through, as I understand it, the govt., thus tax-payers will pay for it. Of course, it will take long, but at least we will know which drug is better and will use that one. As far as the cost of the drug goes, as I understand it, the cost of Avastin will still remain low, if the Nat. Eye Insti. funds the study. However, if Genentech were to undertake the study, it would obviously increase the cost of the drug to recover the amount spent on clinical trials, and then some.

I think that if an unbiased person, with no finanical gains from the results of the study performs it, we stand to get a better answer. If he/she reports that Lucentis is indeed better, no problemo, we'll keep using that. If they say Avastin is better, then what happens? Maybe Genentech can start producing Avastin only in smaller doses which can be used in both colon cancer and introculary, thus making it available for intraocular injections, and increase the cost of Avastin for intraocular use to that of Lucentis? Thus, both the patient and Genentech will be happy. The patient because he/she gets the better drug, and Genentech because they can make twice the money from Avastin. As for Lucentis, well, it could be the alternative. Since it is debated which has a higher affinity, a genetic mutant will surely be reported which responds better to Lucentis than Avastin, thus making Genentech even happier. ( and not to mention the mutant patient whose sight will also be saved).

So in the end Sqrl thinks she's made everyone happy. (she is conveniently forgetting insurance in the mis, and she realises that. But that is something beyond her understanding. Perhaps someone else can help).

With that said, Sqrl goes off to watch Ugly Betty.

References:

http://www.bloomberg.com/apps/news?pid=20601087&sid=aKK8VkXWwTLU&refer=home

http://www.sfgate.com/cgi-bin/article.cgi?file=/chronicle/archive/2006/10/05/BUG1LLIKVG1.DTL&type=business

http://content.nejm.org/cgi/content/full/355/14/1409

http://content.nejm.org/cgi/content/full/355/14/1409/DC1

HAVE to listen to the last one..

and this one