Replies to post #339 on Biotech Values

[DewDiligence]

Re: Macugen phase-3 results:

These are my preliminary comments based on this morning’s Reuters newswire. I would like to reserve complete judgment until we have the additional details in the press release from Pfizer/Eyetech.

>> Macugen, a drug being developed by Pfizer Inc. and Eyetech Pharmaceuticals Inc., was 27 percent more effective than placebo at limiting vision loss [emphasis added] in patients with the "wet" form of macular degeneration in a late-stage trial, said Dr. Carmen Puliafito, director of Bascom Palmer Eye Institute in Miami and the study's lead investigator. <<

Right off the bat, I notice that Dr. Puliafito is talking about limiting vision loss rather than actually improving vision.

Let’s back up for a moment: in GENR’s Squalamine AMD trial, the data were placed into three categories: 1) Improved vision (gain of 3+ lines); 2) Stable vision (gain of less than 3 lines or loss of less than 3 lines); and 3) Vision loss (loss of 3+ lines). (Squalamine had no patients at all in group 3.)

The Macugen data, however, are being presented with only two categories, where categories 1) and 2) above have been merged into a single category called “improved or stable.” Presumably, when the PFE/Eyetech PR comes out it will say how many patients actually had improved vision; however, it is reasonable to infer from Dr. Puliafito’s comments that the percentage of patients with improved vision is small or this number would have been given to Reuters.

>> "VEGF is probably the most important biologic mediator of blood vessel growth. Now we have antagonists that can block that action," Puliafito said. <<

Again, what’s notable is what Puliafito did not say. Macugen can block the action of VEGF, but Squalamine can block the action of multiple growth factors including VEGF.

>> "The trial took all comers. The results imply that we are going to have a treatment for most patients with wet AMD” <<

Taking “all comers,” rather than segregating the patients by disease subtype, may cause some problems with the FDA. Please see message #298:
http://www.investorshub.com/boards/read_msg.asp?message_id=1721160

>> The drug, given every six weeks by injection directly to the eye, stabilized or improved vision in 33 percent of patients, compared with 23 percent on placebo, according to the 54-week late-stage trial of 1,168 patients. Seventy percent of Macugen patients achieved the trial's goal of limiting vision loss to no more than three lines on an eye chart versus 55 percent of the placebo group, Puliafito said. <<

In other words, 70% of Macugen patients had improved or stable vision (based on the definition given above), but an unknown percentage of patients (probably a small % or they would have touted it) had improved vision. That leaves 30% of patients who suffered vision loss of 3+ lines. Although this is a better outcome than the 45% of placebo patients who suffered vision loss, it is hardly impressive to have 30% of patients losing a significant amount of vision when you consider that Macugen was administered every six weeks throughout the study. Regardless of how these results might be spun, I am decidedly unimpressed.

Now let’s talk about safety:

>> Side effects of Macugen included a small number of eye infections… <<

How many is small? Tell us the exact number, please. FWIW, here is what it says about Macugen safety on Eyetech’s website:

http://www.eyetk.com/clinical/clinical_index.asp#7

>>
Before a physician administers the injection of Macugen™ (pegaptanib sodium) the patient will receive a topical numbing drop that may sting slightly and then a pre-injection of a local anesthetic that totally numbs the eye. The entire process from initial drop through injection of Macugen™ (pegaptanib sodium) takes under five minutes. As the specialist administers the medication (equal to about two drops), one may experience some pressure in the eye, soreness, itching or blurring of vision. Possible side effects of the procedure and the administration of drug may include cataract formation, glaucoma, damage to the retina or cornea, bleeding and the possibility of an eye infection.
<<

Infections can usually be treated, but some of these side effects are serious business –tell us the incidence rates, please.

In summary (with the caveat that I am reserving complete judgment until seeing the press release by the companies themselves), it looks like Macugen can be downgraded from the main Squalamine competitor in AMD to an also-ran. If these Macugen data are all there is, I am now more concerned about Lucentis than about Macugen.