You remember 1999 and 2000, don't you? The internet stocks got a lot of attention, but there were plenty of biotech wonders on NASDAQ, too. The genomics wave was cresting at the same time as several other technologies, and people were just caught up in the excitement of it all. Dozens of wonder cures were going to come spewing out of the human genome, and this glowing future belonged to the young and the fast. That's basically the only way to explain how Human Genome Sciences hit the prices it did.
The genome hype collapsed at roughly the same time as the early Internet hype, by one of those little jokes of history, and HGSI had to go out and earn a living. They've been trying to turn themselves into a good old biotech company, but their most advanced clinical prospect just hit a major air pocket. Somewhere around fifty per cent of the stock's remaining value evaporated when they announced that their therapy for lupus missed its Phase II endpoints.
They were going after a target protein called beta-lymphocyte stimulator, or BLyS. It's required for the survival of that variety of white blood cell, and if you cause mice to overexpress it, their revved-up beta lymphocytes give them an autoimmune disease rather similar to lupus. Humans with lupus often show elevated BLyS levels, too, making it one of the prime candidates for a new therapy.
Well, so much for theory. HGSI's LymphoStat B antibody neutralizes BLyS, all right, but that doesn't seem to be enough to slow down lupus. The treatment failed to lessen lupus symptoms or reduce the number of acute attacks. The company says that they did see some trends toward symptomatic relief, but it's clear that they were hoping for a lot more than that. They're talking about plowing ahead into Phase III, but Glaxo SmithKline (who would be paying for a lot of that) is sounding more cautious about the idea, as well they should.
So, what role does BLyS play? One theory has been that it's the main causative agent, but that's now been shot down. Another idea was the a certain level of BLyS was necessary for the autoimmune condition to take hold, but that it wasn't a player in the actual mechanism. (Recall that not all lupus patients show elevated BLyS levels). I don't know what shape that idea is in, because if it's true, then the patients who have just barely enough BLyS to support the disease state should have responded, and it doesn't sound like they saw that, either.
No, while the understanding of lupus (and other autoimmune diseases) has advanced because of this trial, it's done so in the toughest way possible. The old theories are in bad shape, and we don't seem to have much to replace them with. Here's hoping that there's something in HGSI's clinical data that might show where to go next. At the rate that they're going through cash, though, they might see this promised land and not be able to enter it. . .