VentureBeat

(UPDATED: See below.)

For at least a decade, biotech futurists have been predicting that the genomics revolution will lead to medical treatments tailored to the genetic quirks of individuals. And for at least as long, we’ve all been waiting for evidence that this “personalized medicine” revolution is coming to pass.

On Monday, the field took a baby step forward when the FDA approved Selzentry, a new AIDS drug from Pfizer. Selzentry is unique in a number of ways — for instance, it’s the first drug that tries to “lock down” T-cells to prevent HIV (that’s the culprit, above and to the left) from entering and infecting them. Fuzeon, a less-than-successful drug from Roche and Trimeris, does something similar, although it works to gum up HIV’s “landing gear,” not the T-cell’s docking port.

But the particularly interesting thing about Selzentry is that it only works against a particular sub-strain of HIV — those that dock to a T-cell surface protein called CCR5 in order to invade. (Most HIV strains use another protein called CXCR4 or a combination of the two.) That means would-be Selzentry users first have to be tested to ensure that their HIV strain will respond to the drug. And that, in turn, makes Selzentry one of the first drugs to be paired with a diagnostic test that limits the number of people who can try it, but which also greatly enhances the odds that it will work in those who do.

That test, offered by Monogram Biosciences, requires “amplifying” the HIV genome in the lab, producing scads of genetically identical viruses that are used to infect cultures of T-cells that lack either CCR5 or CXCR4. When infection occurs, a transplanted gene in the cell cultures begins to produce fluorescent proteins, making it easy to tell whether the viral strain is CCR5-specific. (There’s more info in this Monogram press release.)

Of course, Selzentry — generically known as maraviroc — most likely wouldn’t appear to work at all if tested in a general population, which helps explain why Pfizer was willing to pair it with a diagnostic. Genentech’s breast-cancer drug Herceptin — long the sole poster-child for the nascent field of personalized medicine — likely would have gone the same way had researchers not realized that it appeared to work particularly well in an identifiable subset of tumors.

So far, however, there aren’t too many other similar personalized treatments out there, or even in development. One exception is the beta blocker bucindolol being developed by Arca Discovery, which aims to test the drug in patients who have specific genetic variants; I wrote about them here.

Why aren’t there more? The simplest explanation is that most drug developers, whether pharma companies or biotechs, don’t want to risk circumscribing their patient population unless they have to, since doing so by definition limits the potential sales of a new drug. Up to now, drug makers haven’t really faced much economic pressure to embrace personalized medicine, or “pharmacogenomics,” as it’s technically known. With pipelines drying up and the patent environment getting a lot harsher for the me-too drugs drug giants have long relied on, however, they may soon have little choice.

(Brief aside: Pharmacogenomics, of course, is also the answer to the oft-touted assertion that me-too drugs — meaning a variety of drugs that all target the same biological mechanism, such as the half-dozen statins approved to lower cholesterol — aren’t the waste that drug-industry critics often assert. This argument holds that patients who, for instance, don’t respond to one statin might actually benefit from a different one. The short and simple response is, Where’s the proof? If the makers of statins, or of the depressants known as SSRIs, really want to know which patients their drugs work best in, it’s certainly within their ability to find out. The fact that no one is conducting such tests tells you quite a bit of what you need to know about decision-making in the drug industry.)

UPDATE: Apropos of nothing, I just stumbled across this Reuters story describing a Royal Society report on personalized medicine. The bottom line:

“Personalized medicines show promise but they have undoubtedly been over-hyped,” said David Weatherall, who chairs the working group that produced the report.

UPDATE REDUX: For more on the FDA’s big push behind personalized medicine, see this more recent post.

Read the rest of this entry »

Baltimore, Md.-based Profectus BioSciences, a biotech developing new strategies to attack HIV, received a $200,000 small-business innovation grant from the National Institutes of Health to improve the effectiveness of anti-HIV antibodies. Last month, the company received a similar $300,000 grant (PDF link), just a few days after the company raised $3 million in a private placement.

Profectus, which was spun out of the Institute for Human Virology in 2005, has so far rased a total of at least $6.5 million.

I’m at work on a longer post that hasn’t yet come together, so I thought I’d pull an old dodge favored by daily newspaper columnists and respond to some reader comments instead. Fortunately for me, both comments left here in the past day or so have been thought-provoking — maybe there’s hope for the Internet after all.

With respect to the tussle over patents and drug pricing in Thailand, Gal Josefsberg wrote:

I’m not sure how they expect to get cheap HIV drugs if the destroy the company’s profits. I know we all think these sort of drugs should be cheap, but there’s an enormous cost to developing and testing them. Without some kind of profit motive, the R&D spent on these treatments will go down. I’m not saying the pharma companies should gouge HIV patients, but just saying “thanks for developing this drug, we’ll take it from here” is not the right answer.

Where AIDS drugs in the developing world are concerned, the arguments tend to be a little more complicated than I may have suggested. Some pharma and biotech companies — I’m most familiar with Gilead Sciences, although I believe others do this as well — explicitly acknowledge that it’s wrong to profit from the world’s poorest nations and set what they call “no-profit” prices for HIV drugs in almost 100 countries. Of course, they still plan to make out handsomely in the U.S., Europe and other industrialized parts of the world.

Things, however, get quite a bit murkier in “middle income” nations like Thailand, where the population as a whole is unquestionably getting richer, but where many of the people who need the drugs most are also still quite poor. Critics argue that it’s the responsibility of the Thai government to help its citizens afford drugs, and while they have a point, I’m not convinced the drug companies are wholly blameless. Many of them have only grudgingly begun efforts to cut poorer nations some slack on the price of life-saving drugs, following years of protest by AIDS activists and international organizations. Given that many activists still think companies like Abbott are trying to profiteer in developing-but-not-exactly-wealthy nations like Thailand, it’s no wonder that distrust of the pharmas still runs high in many quarters.

By the way, Brazil has apparently issued a similar threat to Merck over its HIV drug efavirenz (via Pharmalot).

In response to an item on the tactics drug reps use to push their product on doctors, RJ notes:

the first paper seems to be describing a phenomenon known as “sales”– truly a beauty to behold when it’s done well. No matter whether you’re selling drugs or enterprise software. That’s why the great sales people are paid so much. They’re artists.

That paper was written so vividly that I couldn’t help but wonder if Ahari, the former Lilly rep, doesn’t kind of miss his old job for exactly those reasons. There’s definitely something awe-inspiring about watching a professional salesperson at work, although I’d feel better about admiring it here if the sales job wasn’t specifically designed to override a physician’s best medical judgment — which is, after all, what the patient needs most and what insurers are supposed to be paying for.