It's not supposed to be like this.
newfangled AIDS drug works well, if the evidence from the clinical trial presented Monday at the annual meeting of the
American Society of Microbiology
holds up in subsequent studies.
That used to be enough for investors. If the data were positive, the drug (especially an AIDS drug) would get approved. Approval would mean good sales for a drug this effective.
But not so fast. Trimeris' drug,
, is an injectible peptide. To meet its plan, Trimeris' partner
will need to manufacture more peptides than are currently manufactured by all other makers combined.
There are so many damn risks in biotech. You gotta worry about management, the regulators, the monster competitors. Now you have to invent a whole new manufacturing technology? On top of that, you have to be able to make the drug affordable?
Scary stuff. Worried about a risk that they've had largely ignored up until now, investors sold Trimeris shares Monday. The stock closed down 3 3/8, or 14%, to 20 5/8. The selling continued unabated Tuesday, pushing Trimeris shares down an added 1 3/8, or 6.7%, to 19 1/4.
Let's look at the data. T-20 is the first of an entirely new class of AIDS medicines called "fusion inhibitors." They attack HIV before it binds with cells in the victim's body. With resistance developing to the current AIDS treatments, which inhibit either the reverse transcriptase or the protease enzymes, a new way to attack the virus is thrilling stuff.
T-20, though early, is causing a bit of a sensation at this meeting. In a Phase II study presented Monday as a late-breaker, the drug showed that it worked and caused no significant side effects. Building on earlier
data, the trial enrolled 71 patients, all of whom had been heavily treated previously. More than half responded to the treatment. Of those who actually got the drug, 60% responded. About a third of the patients who responded saw their viral loads, the amount of virus in the blood, fall below 400 copies of the virus per milliliter, below the level of detection.
The treated patients showed a reduction of viral load of 1.2 orders of magnitude on average at 16 weeks. The drug's dose is 50 milligrams, taken twice a day. "The drug shows a lot of promise. That's why we need the next set of trials," says Michael Saag, a top AIDS specialist from the
University of Alabama at Birmingham
The drug is going to be used in patients for whom the current cocktails of therapies have failed. As resistance grows, this population grows as well, making it an increasingly attractive market.
The companies are embarking on a four-arm Phase II trial. It will have 17 patients in each group, testing three different doses of T-20. Analysts think that if things go well, the drug could be on the market in the middle of 2002.
But to be a success, the company's going to need to make a whole lotta peptide. It's not like Trimeris and Roche don't know about the challenges to increasing manufacturing capacity to accommodate T-20. "The partnership with Roche was essential," says Dani Bolognesi, the company's newly installed president and chief executive and a major cancer researcher himself. "There is no paradigm for manufacturing the drug. For us to consider doing it ourselves would have been foolhardy. If you add up all the peptides made in the world today, it's maybe 500 kilograms. We have to be above that -- in the metric-ton range."
He adds in the cautious way of a professor (so unlike the typical biotech CEO): "We are fairly confident that we are on track for all of the trials. The beginning phase is obviously tricky." Originally, he says the drug cost about $11,000 a gram to produce; now it's more like $300 a gram and going lower. The company is studying reducing the dose and different formulations as well.
"We expect significant demand," says Frank Condella, a vice president at Roche who is spearheading its T-20 effort. He says Roche will consider all options on making the drug, including possibly building a new plant for T-20.
There's plenty of skepticism. "A lot of these stories come down to very simple concepts," says Kellie Seringer, a biotech analyst for
who attended the presentation, but doesn't cover the company. "You can have all the data in the world, but it doesn't matter if you can't make it."
But a hedge fund manager who has a major position in Trimeris thinks Roche will be able to pull it off. "Roche says there's no doubt they'll be able to make one ton in 2002," the manager says. "I think they'll be able to make two, maybe more." He says the company has an idle plant that it can use for the drug, adding, "They don't seem too concerned about scaling up." He says the bigger issues are logistical ones, like signing deals with raw-materials suppliers, rather than technical ones.
Perhaps. If the challenge proves beyond Roche's capabilities, all isn't lost. Trimeris has a follow-up compound. It appears to be more potent, to work its way through the body more easily and to have a better resistance profile, because it binds more tightly. Says the normally conservative Bolognesi: "This baby is a very nice advance."