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Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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September 17, 2006

Tough Targets

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Posted by Derek

Novartis has been looking pretty impressive lately. They've announced promising data for their odd immunosuppresive drug Fingolimod (FTY720) in multiple sclerosis therapy. The study isn't very large (255 patients), but the statistics versus placebo look pretty strong. The compound is also showing promise in transplantation, and no doubt the company is looking into other autoimmune disorders as well.

I should note that the drug's target (which appears to be a sphingosine phosphate receptor) wasn't known for many years. It started out as a structural variation on another compound with known effects, it but turned out to have a different (and more useful) profile. This one, if it works, will be more a triumph of persistance and deep pockets rather than drug design, but we'll take 'em where we can get 'em.

The company also has reported data on a new bisphosphonate (Aclasta, aka Reclast) for osteoporosis, notable because it's only dosed once a year. This one had over seven thousand patients, followed for three years, so it's a substantial piece of work, with what appear to be very strong statistics indeed. Novartis appears ready to hammer Fosamax (aledendronate), which has been coining money for Merck for many years now, since they specifically studied a subgroup of patients who were switched from that drug.

One of the notable things about these two drugs is that they're addressing chronic, slow-moving diseases with difficult clinical endpoints. These therapeutic areas are tough to work with in the clinic, and very costly to explore. There are many companies in the industry that would immediately try to outlicense a new osteoporosis clinical candidate rather than try to develop it themselves. You won't see many small biotechs trying to go it alone in areas like this, that's for sure.

So even though I make fun of Pfizer (especially) for being too huge, Novartis is one of the counterexamples. They (along with Merck and GlaxoSmithKline) show that size can have advantages, if you use some of that muscle in the research buildings. FIguring out why some large research organizations are more productive than others, and what part of that isn't due just to chance, has stumped better pundits than me, though. . .

Comments (5) + TrackBacks (0) | Category: Business and Markets | Clinical Trials


1. fubar on September 17, 2006 9:31 PM writes...

Wouldn't a new bisphosphonate have to make it's case against alendronate, given the status of the Teva/Arrow Generics suit against Merck's patents? A new compound in a market served by a generics is a tough play for the sales guys.

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2. SC on September 17, 2006 9:52 PM writes...

On the other hand, it's hard to argue with once a year dosing. Patients would love it. And compliance would be a relative non-issue ("Well, Mrs. Jones, just be sure to come in next year at this time for your next dose, right after your Bone Density Scan").

And it's hard to imagine any sort of pricing that would make that sort of pricing schedule significantly out of line with competitors and possibly even generics when taken as the "cost per year".

This could turn out to be a real winner. Novartis is looking very strong indeed, with upwards of seven major launches targeted in the next two to three years.

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3. Chrispy on September 18, 2006 2:31 PM writes...

Once a year? I had heard that the side-effect profile of these bis-phosphonates was not that great. What do you do if your jaw starts to suffer from osteonecrosis in month one?

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4. MTK on September 18, 2006 5:24 PM writes...

The study as reported specifically mentions jaw side effects as being "comparable to placebo" and that most side effects observed were within days of intial dosing and then dissipated.

I remember that it was about 5 years ago that someone published that they could see good results with bisphosphonates with once-a-month dosing in a very small study. This, of course, raised the possibility of even more sporadic dosing of bisphosphonates. Does anyone know what the mechanism here is? I'm not an expert in this area. It's good to see some academic work getting translated into real clinical results in a reasonable timeframe for this type of long-term indication.

Anyway, if this holds up oral Fosamax/generic alendronate is dead. Compliance is a huge problem with alendronate. You have to take it with 8 oz of plain water and you have to sit upright or stand for 30 minutes after taking it. Even at the once/week dosing this is a chore. The labeling might as well say, "Do the hokey-pokey."

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5. Petros on September 19, 2006 3:15 AM writes...

Bisphosphosphonates have funny PK, probably due to their low bioavailability. But slow release from a depot seems to be effective and the market has recently been dominated by wekly formulations.

Since the target population is elderly less frequent dosing is proably advantgeoues. Roche's Bonviva is the first monthly drug in this class and a yearly injection makes sens for the reasons already mentioned.

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