More Tough Times

It has not been an easy time in the Research Triangle Park area but we got some more bad news this week. I heard a report that High Point chemical synthesis company PharmaCore had let people go last week. I don’t seem to be able to find any confirmation of that anywhere. Then I also heard yesterday that biotech company Grifols (which acquired Talecris in RTP not too long ago) has shed more R&D positions here. Again, a lack of news source, but since I actually know someone involved, I am pretty certain of my facts there.

What with the decline of GSK in the area, plus the relocation of Pamlico last year, the biotech/pharma industry has been hurting in these parts.

Best of luck to all of those involved.

NIH NCATS Drug Repurposing

In his latest Forbes column, John LaMattina makes a number of very good points over the NIH plan to take existing drug candidates and use their resources to look for new applications that they may treat.

As LaMattina says, this would be great if it worked, but is it really likely and is there a better way that NIH could be spending its precious resources? Is this sort of sifting through the dusty shelves of the pharmaceutical industry panning for gold really what the NIH should be doing? I see this as the sort of activity a small start-up forms around, takes a chance on their find and then lives or dies. It is more than a little risky.

Curious Wavefunction makes the point (while broadly agreeing with LaMattina) that the pharma industry is not really doing all it can to discover new drugs, putting next quarter’s revenue forecast over a more long term outlook and it is hard to deny that the pharmaceutical industry has been rather self-destructive lately.

However, re-examining old drug candidates can’t be the best use of NIH funds. It is there to spur the research, the basic research, that will eventually lead to a practical impact upon society in the form of new treatments, new prevention, or things we can’t yet imagine. The old Molecular Libraries Program – now being phased out in favor of NCATS – made a stuttering start but my impression was that it was doing the right things, making high-through-put screening, modeling and some medicinal chemistry available to academia. Indeed, folks at Vanderbilt had praised its importance to their academic drug discovery program. The screening sites set up under this initiative now need to find their own funding which may be difficult in the current climate, but there has been some collaborative work with industry as industry also needs innovation in order to feed their dwindling pipeline. Pfizer has its Centers for Therapeutic Innovation, as well as a number of academic collaborations. Eli Lilly has its Open Innovation program. Other companies have made efforts in this area too.

However, it has to be said that the main player in starting the basic research programs that result in such innovation has historically been NIH and it seems to me that even a scaled back version should concentrate on its core function.

Hard Road for Neuroscience Research

Via Chemjobber, C&E News have an article on the number of cuts in neuroscience research recently, a subject I have been meaning to blog about. As an aside, I haven’t read the C&E article (no access), but am relying on CJ’s precis. So with my scoop already busted, I soldier on.

The list is a catalog of Big Pharma research efforts shut down after review or merger. It makes for depressing reading for anyone working in the area (or hoping for progress), but it is not really that surprising. Neuroscience is notoriously difficult to get an approved drug out at the end. Expensive failures abound.

Pretty much every seminar I go to in my work area starts with Rimonabant. It was all set to be the next blockbuster, an anti-obesity drug that showed excellent results in clinical trials. It worked as a cannabinoid receptor antagonist, effectively blocking the effect of marijuana on the brain, known for euphoria but also giving you the munchies. It was even approved in Europe, but was subsequently withdrawn when the side effects, which included depression and suicidal thoughts, started to outweigh the benefits.

Another dangerous area of research is in Alzheimer’s Disease, a notoriously difficult condition to treat. Several drug companies have tried and failed, with two candidates making this list of Phase III failures, Lilly’s semagacestat and Pfizer’s Dimebon. A big problem here comes down to the drug companies having an idea of how to treat the disease (targeting an enzyme called gamma-secretase which forms beta-amyloid plaques in the brain) but no proof that it actually works. The human body in general is not completely understood and the subtleties of our biology are breath-taking, but nowhere else is still so mysterious as what goes on inside our own heads. Somehow that makes drug companies reluctant to pour more money into research.

However, despite these setbacks, Merck announced this year that they will file a new drug application for suvorexant, which is a sleep disorder treatment based on antagonism of the orexin receptor in the brain and they look promising as an improvement over GABA inhibitors like Ambien. Even this was not without its problems, as the compound most advanced in clinical trials, Almorexant, was withdrawn.

Despite it being an area where there is a very real need for more medicines, it is easy to see why drug companies are looking elsewhere when the pipelines and research budgets are shrinking.

No Such Thing as Low-Hanging Fruit

There is a theory that drug discovery is harder now, that we aren’t getting more and more blockbuster drugs because the easiest targets to make effective drugs for have already been exploited – the so-called low-hanging fruit. And so, as the theory goes, finding new medicines is fraught with failure and disappointment.

John LaMattina tackled this in his latest blog post on Forbes. As a side-note, his blog both before and after moving to Forbes is well worth a read for anyone interested in drug discovery.

His take is that there are countless stories of drug discovery projects going awry and there always have been. In hindsight, it might seem obvious and easy, but when it was going on, plenty of things were hard and did not go as expected. The example of prostaglandins he gave was poignant for me, as even in my undergraduate we were talking about prostaglandins and their importance. Though of course, they were cool little molecules to synthesize as well – I ascribe the A I got in the natural product synthesis class to the synthesis I had of that molecule in my final exam.

My take on the low-hanging fruit issue is not that the easiest things have been found but more that the level of care we can provide now is much higher and so the bar for entry in a particular therapeutic area is correspondingly higher as well. If things had gone differently, it might be that drugs we have today would not make it through clinical trials because of the side effects in comparison to the other drugs we had already. Would acetaminophen make it to market if it was discovered today? Would beta-lactams, a drug series that many people can’t tolerate? Something interesting to ponder.

Pamlico has Left the Building… er… State

More local chemistry woes, as I heard local company Pamlico Pharmaceuticals had closed doors locally here and moved their operation to New Jersey.

Oddly, I have been unable to find any official confirmation of that and the Pamlico website still shows them as an RTP company. They were financed not by venture capital but by backing from a Chinese company, so it is likely that the move has come from there. Or they set up a place in New Jersey as well and decided that keeping both sites was superfluous?

Either way, more bad news for the Triangle scientific community – good luck to those that got laid off as a result.

Drugs Are Expensive

We already know the cost of buying pharmaceuticals is very high, seemingly climbing higher and higher. Well, says the industry, they cost a lot to discover. The number that was always quoted was $1 billion. Which is quite a lot, but according to Bernard Munos (posted by Matthew Herper at Forbes), the actual figure is much higher, from $4 billion all the way up to $11 billion.

The difference comes from taking into account the failures as well as the cost of taking on a project from start to finish. That process is not cheap (with a large chunk of money going into the clinical trials prior to approval), but the ones that make it all the way to the end are really the exception. If you look at the research budget for the company as a whole and look at how many drugs came out from that spending, it is jaw-dropping how much money has been spent in the pursuit of an approved drug.

And you can see why the pharmaceutical industry wants to try and get some of that investment back, even as that course of treatment spirals up and up in cost.

Astra-Zeneca Lay-offs

Friday got busy and I didn’t find the time to blog about the announced lay-offs (and site closings) at Astra-Zeneca – over 7,000 announced and further plans for their main US site at Waltham, MA. As usual, both Derek (who gave a second post about Waltham) and ChemJobber made excellent points about the situation.

It is an ugly situation not helped by the company’s handling of it. Once again, a productive group is broken up in Montreal. And the main site at Waltham is befuddling, driving morale down even lower and (even better) encouraging the employees to jump ship if they can. And who are most able to jump ship? Your best employees, the ones that if you were going to slim down and become more efficient, that you’d really like to keep. Nice going, AZ.

The twist in the knife in the back is the stock buy-back plan. Cutting resources to spend that on shoring up the stock price is remarkably short-sighted, even for the bureaucrats and financial geniuses that dwell at the top of most of our scientific endeavors these days.

Best advice to those waiting under the axe (and indeed to many of the rest of us) is work on your papers, building a network, a fleshed out LinkedIn profile. Learn a new skill. Doing something to improve yourself is better than waiting anxiously out in the cold.

Good luck to all.

Sad News From Scynexis

Sad and bad news for the RTP scientific community this week, as Scynexis laid off 12 people this week.

Now in the grand scheme of things maybe 12 people is not so many but here it was quite a hit. Scynexis along with GSK are the main employers of organic chemists in the Triangle. Although with cuts at both places now, I am no longer sure who employs the most any more. So that is an indicator of the local job market. More personally, I know many of those laid off and I know it had to have been really hard to let them go. Sad day.

I’m keeping all the folks down there in my thoughts, both inside and outside the company. Good luck to all of them.

Medicine TEDTalk Takedown on Chemistry Blog

I read the blog post by Azamanam about a proposed way to reinvent the pharmaceutical industry, given as a TEDTalk by Thomas Pogge, with increasing incredulity. If you have not, go read Azamanam’s piece.

The fellow appears to have absolutely no idea how the real pharmaceutical companies work. Importantly, he doesn’t seem to realize what it takes to discover and, importantly, develop new drugs. It is a hugely costly endeavor, fraught with unexpected difficulties and can fail at the last hurdle. In fact, it can fail after the last hurdle when further exposure to the population at large reveals new side effects. Given the enormous expenses and the number of projects that just never make it to market, I find it entirely unsurprising that pharmaceutical companies charge so much more for a drug than the cost for making it. Because you are not paying for the costs of the goods inside the pill, but also for the research, effort and time that made that particular combination of chemicals possible.

Noted in Passing

The first day after Lipitor’s patent expired and the news is filled with talk about the measures Pfizer are taking to protect their market share against the generic competition. I had predicted that Big Pharma would be more proactive in promoting their newly off-patent medicines and, while Lipitor may be a special case as the biggest seller, I am sure other companies are watching the outcome with interest, to see how successful they might be in retaining some of that revenue.

Talking of things I wrote about before, I saw that Astrazeneca are putting more funds into their VC arm, MedImmune Ventures. The senior managing director, Ron Laufer, noted that “there is a growing role for corporate VC funds”. All the Big Pharma have these investment vehicles and they are going to be increasingly important with less internal R&D going on.