Biotech Values

[DewDiligence]

Improved vision vs stable vision:

[This is a repost of messages 56807-56808 on the Yahoo GENR board, which I posted in reply to a post by ‘macd_slope’.]

>> [macd_slope]: The 207 study showed that the VA at EOT [end of treatment] was positive or stable for 100% of the patients… Now perform a thought experiment and imagine that squalamine is indefinitely dosed with the result that the VA score is positive or stable practically indefinitely. <<

The tremendous promise of the Squalamine results from Mexico was Squalamine’s ability to improve vision, not merely to stabilize it. At two months from baseline (one month from the end of treatment), 33% of Squalamine patients in the Mexican trial had improved vision, defined as a gain of 3+ lines (15 letters) relative to baseline. At four months from baseline (three months from the end of treatment), 26% of Squalamine patients in the Mexican trial still had improved vision, using the same definition.

In the phase-1/2 Lucentis trial, which reported data in August 2003, patients received three to six monthly treatments, depending on the trial arm they were assigned to and whether they elected to continue in an open-label trial extension. After 210 days, 45% of patients had improved vision on a per-protocol basis, and 34% of patients had improved vision on an intent-to-treat basis, using the same definition of improved vision as in the Squalamine trial:

[Genentech PR]:
http://www.gene.com/gene/news/press-releases/display.do?method=detail&id=6487

[My analysis of the data]:
http://tinyurl.com/29h6g

Talk to ophthalmologists who treat patients with wet AMD and you will hear that the “holy grail” in this disease is --and always has been-- the ability to restore lost vision. This is what patients desperately want and it’s what patients, insurers, and Medicare will pay big money to get.

Thus, I find it disconcerting that, all of a sudden, Dr. Levitt and an array of GENR longs on the message boards are no longer crowing about Squalamine’s ability to deliver improved vision but rather it’s potential to maintain stable vision. The reality is that, for many AMD patients, “stable vision” is a euphemism for stable bad vision. By the time many AMD patients seek treatment, vision is already dreadful.

For Squalamine to compete effectively with Lucentis and become a big commercial success, it is imperative that Squalamine produce improved vision in at least a sizable minority of patients. A drug that merely allows for stable vision, with little or no chance of improved vision, is unlikely to become a blockbuster. By the end of the decade, there may a dozen or more drugs on the U.S. market to divide the wet AMD pie, using various formulations and delivery routes, each capable of stabilizing vision.

If the thrust of GENR’s AMD program has shifted from improved vision to stable vision, as Dr. Levitt hinted at the Rodman & Renchaw talk, the ramifications for shareholders are substantial. A partnership deal can presumably still be struck, but it might be with a second-tier pharma company instead of one of the top names. Such a deal will probably not command an aggregate deal value in the many hundreds of millions of dollars, as many people here appear to be counting on.

Many posts on this [Yahoo] board during the past couple of days seem to be employing creative arguments to rationalize what are mediocre early data at the new 10mg dose. I don’t buy these arguments, no matter how creative they may be.

A better argument is that the sample size in the 10mg cohort of the “207” trial is only six patients, and six patients are too few to produce statistically meaningful results. However, this begs the question of why GENR elected to reveal these data, specifically. Normally, companies show their best data, not their worst, especially when the data release coincides with a financing deal.