Looking through my files, I found a chart which I clipped out of a pharmaceutical magazine back in late 2004 or so. It’s a table of expected drug launches and sales potentials, based on data from Mehta Partners, the well-known (and often-quoted) pharmaceutical-sector investment and consulting firm.

It’s hard not to avoid a feeling of “those were the days” when you look at some of the names on the list. But now that we’re in the last quarter of 2006, this little document has gone from looking hopeful to looking downright creepy. Its Y axis is sales potential, divided into eight tiers, and the X axis is a timeline, quarter-by-quarter. Let’s take it from the upper left corner and look at what the inhabitants of distant 2004 expected the big winners from 2005 and 2006 to be.

The first candidate is Macugen, expected launch 1Q 05, sales potential $1.25 to $1.5 billion. The reality: the launch went off pretty much as expected, but the sales, well . . . they’re running at about 10% of that peak estimate. You may remember that OSI bought the drug’s developer, Eyetech, and people wondered at the time what they were thinking. Perhaps OSI is wondering now, too. This doesn’t seem like an auspicious start to the list, but come back to this one after a few more and see what you think — at least it reached the market.

Next up is Indiplon, expected launch 4Q 05, sales potential $1.25 to $1.5 billion. The reality: oh, dear. This was, of course, the subject of a spectacular blowup at the FDA earlier this year. The most highly anticipated versions of the drug were given the dreaded “approvable” letter, which was enough for Pfizer to pull out of the collaboration. Neurocrine is still in there pitching, trying to go it alone until they find a new partner, but this has been a real development disaster.

Let’s pause a moment to note that both of these first two candidates were printed in green type on the original chart, which means that they were considered “low risk” at the time. After meditating on the implications of that statement, we move on to:

Edifoligide, expected launch 4Q 05, sales potential $1.25 to $1.5 billion. The reality: Aaargh. The drug, an oligonucleotide “decoy” designed to tie up a particular set of transcription factors involved in vein graft failure, completely missed its clinical endpoints in a major trial. Bristol-Myers Squibb dropped it; its developer (Corgentech) went through a near-death experience and emerged with a changed name and an (appropriate) focus on pain management. This one will never be seen again, from the looks of it.

Then we come to Acomplia, expected launch 1st half 06, sales potential $1.5 to $2.75 billion. The reality: gosh, remember when this drug was going to be launched in the U.S. this year? It’s slowly, slowly creeping into the market in Europe. But no one has any idea of when it might be approved over here, where most of that money in that forecast is going to be made (if it ever is). Sanofi-Aventis, despite visible impatience from its investors, has been extraordinarily uncommunicative on the issue. It sure doesn’t look like a 2006 launch, that’s for sure. Next year? You’d think, but that’s what they thought last year. . .

Next on the chart is Plavix (for the Japanese market), expected launch 1st half 06, sales potential $1.25 to $1.5 billion. The reality: they made it to Japan in May of this year, but the cost has been heavy enough to warrant comment in Sanofi-Aventis’s financial statements. And, of course, Plavix and its profits have been making the news for other reasons entirely, but who could have foreseen the current Apotex craziness back in 2004? (Not even Apotex, most likely.)

Rounding out the expected big hits is Asoprisnil, expected launch 2nd half 06, sales potential $1.25 to $1.5 billion. The reality: who knows? Takeda/Abbott and Schering, after some clinical difficulties, have written off 2006 and refuse to say when the uterine bleeding drug might be submitted for approval. Judging from the lack of recent statements, the outlook isn’t good. I’d be willing to bet that we’ll never hear about this one again, but even if I’m wrong about that, it’s going to be a while.

OK, so far we have, by my count: one expensive success, one disappointing success, one serious delay, one near-catastrophic failure, and two wipeouts. But hey, that’s just the most profitable section of the chart, no big deal. Let’s try the ‘mere’ billion-dollar drugs in the next tier and see how that goes. All of the following were listed as having sales potentials of $1.0 to $1.25 billion:

First up is Avastin (for the EU market), expected in 1Q 2005. And, wonderful to report, that’s exactly what happened. Right after that, also in green low-risk type, is Ambien CR for 2Q 2006. That made it in the third quarter which, given what’s on the rest of the chart, is hardly worth mentioning. It’s a bit early to say how the sales are going, but Sanofi-Aventis’s first half results for it looked reasonable. Two for two!

Don’t relax yet, though, because the next drug on the list is muraglitazar, which was expected in 4Q 2005. Instead of approval, the fourth quarter of 2005 saw the release of troubling cardiovascular clinical data. By 2Q 2006 the drug was dead, with Bristol-Myers Squibb and Merck deciding to cut their (substantial) losses. The PPAR alpha-gamma field has been a slow-motion demolition derby, and this compound is merely the latest ruinously expensive crash.

And, unfortunately, the next one up is PTK787, from Novartis and Schering AG, listed for the first half of 2006. That one ran into all kinds of trouble in its Phase III trials for colon cancer in 2005, and looks like it may never realize the hopes that the two companies had for it. We won’t see it for quite a while, if we ever do (which at this point I rather doubt).

And finally, the chart rounds out the second half of 2006 (also known as “right now”) with Pfizer’s varencline for smoking cessation (approved!), and three antipsychotics: asenapine from Akzo and Pfizer (still in the clinic), Wyeth/Solvay/ Lundgren’s antipsychotic bifeprunox (now expected next year), and paliperidone from J&J, which is in approvable-letter limbo as I write. It’s too early to say how these three are going to work out, so I’ll defer comment and only note that none of them are on the market yet.

There we have it — step back for the full effect. Overall, despite a few correct calls, this 2004 rundown is mostly a cornucopia of missed timelines (at best) and expensive disasters (at worst). But I’m not blaming Mehta Partners for this at all. They did what they could with the best information they had, which was mostly from the companies involved. The companies aren’t completely to blame, either — they really believed that these things were going to work, and they put a lot of their own money down on those opinions. No, it’s hard to find one party to soak up the blame: all it does is graphically illustrate just how hard R&D is. But just think about how many investment decisions were made (are made!) based on such forecasts, and shiver a little.

Derek B. Lowe has been employed since 1989 in pharmaceutical drug discovery in several therapeutic areas. His blog, In the Pipeline, is located at http://www.corante.com/pipeline and is an invaluable aid to Contract Pharma. He can be reached at [email protected]