Org Prep Daily

September 6, 2007

Copycat drugs

Filed under: industry life — milkshake @ 1:13 am

storks.jpg Credit Jiri Sliva

Levitra is a close Viagra knock-off and there is little difference between the two for the patient. “Money wasted on developing yet another version of the erection pill could have been put into malaria research instead.” And so on.

I am not a fan of Big Pharma but I would like to point out that the misery of the Third World was not caused by the lack of drugs or by their high prices - the root problems have to do more with awful governments and wars. But if most patients there cannot pay for the new antimalarials / HIV inhibitors / tuberculostatics, the research interest will get re-directed elsewhere and one can hardly blame the industry for that.  (Another complication is that even if the drugs are provided for free, it is hard to get these patients to take their medications in a disciplined manner for the prescribed period of time - and hence the multidrug resistance emerges soon)

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Sepracor business plan used to be entirely based on patent-busting; Sepracor was scorned for it by many people in the industry. Yet this kind of “bottom-feeding” research saved some good drugs from oblivion - drugs that would not be introduced into US otherwise. As a result, a next generation of drugs appeared in previously stagnant fields. (Antihistaminics, sleep meds.) 

A competition from me-too drugs produces pressure that pushes the innovation - without it, companies selling popular drugs are in no hurry developing their more advanced follow-on candidates if their established drug is doing fine. 

A late-comer drug needs to offer some demonstrable advantage over the more established ones. The me-too drug can for example have a different pharmacology from the original drug – whether this was a part of the design or just a coincidence. (The drug distribution, metabolism, drug-drug interactions and side-effect profile are notoriously hard to predict: a small change in the structure can have an important effect which might not be apparent until the testing is done in patients). The main reasons for doing the me-too medchem research is that it is a lot easier: Developing a new structural class from a low-potency screening hit can take years and there is no guarantee that this optimization will ever produce a drug candidate. Starting with a proven competitor’s compound and modifying it in few places greatly shortens the development time and improves the chances of success. 

It is just impossible to exhaust all possibilities inherent in a class of molecules. The chemists and biologists in the team that discovered the original drug must have made choices at numerous points of the project- when they picked the directions they thought were worth pursuing. Their project had deadlines, it was influenced by personal experience and bias.  Independent re-visiting the original data and premises with the hindsight knowledge of the clinical performance and with a competitive mindset can lead to surprises, and eventually to an improved drug candidate.  

There is also a natural tendency of compounds coming out from different groups to converge:  It is a common practice in the industry to re-synthesize and test the published compounds. The added insight from their testing (especially when combined with the X-ray crystallography) can quickly close the gap between the competing groups. This can also produce a resemblance of a me-too approach.

6 Comments »

  1. “Sepracor business plan used to be entirely based on the patent-busting and for these audacious efforts Sepracor was derided by the rest of the pharma industry.”

    They produced this patent. Do you think it deserves derision?

    Comment by Zeph — September 6, 2007 @ 9:30 am

  2. No. Their chemistry was always first-rate. I had them in high regards since the school because of the early adaptation of asymmetric synthesis in process scale-up. When I was interviewing years ago in the industry, Sepracor was on the top of my list – I was asked during the later interviews about which companies I visited so far and just mentioning the Sepracor name at few major companies caused a hissy response from medicinal chemists. The “bottom-feeders” was the one that I remembered clearly :)

    Note: I just re-wrote the end of that sentence a bit, to make it less suggestive of ‘the prevailing mood in the industry”.

    Comment by milkshake — September 6, 2007 @ 9:38 am

  3. What did Sepracor do that could not have been done in-house by Big Pharma? Any of them could have massively reset their patent dates – and seized those of their competitors – with chiral prep HPLC. It is more sour grapes than bottom-feeding.

    Polymerizable UV absorbers are heavly patented. The entire galaxy of prior art was broken by using an SOP molecule as a polymerization inhibitor. The degree of MW suppression was monitored by UV absorption. It was OK for the stuff to be permanently bonded afterward.

    Uncle Al’s reward was a write-down because the project assignment was not fulfilled – finding a suitable new UV absorber outside competitor patents. Nice.

    Comment by Uncle Al — September 6, 2007 @ 3:49 pm

  4. It’s funny- I’ve wonder if the lawyers that wrote the Pfizer patents for Viagra still have jobs? I guess Levitra hasn’t made too much of a dent in the bottom line, but still….

    Comment by Jose — September 6, 2007 @ 6:16 pm

  5. Their chemistry was always first-rate.” That implies that the patent I referenced works.

    Comment by Zeph — September 7, 2007 @ 8:37 am

  6. I am not familiar with the Taxol patent situation and how it relates to the IP from other companies so I cannot comment on this. I know that Sepracor did try to patent whole lots of stuff that was “improved version” of somebody else drug – and I wonder how much of that was solid – or how much of it was a general idea plus prophetic examples. That’s their business model and if they exploited a weakness in the patent law and laziness of some Big Pharma companies, I say good for them. When I interviewed there I did not have the most pleasant feeling about the place yet I though what they were doing was worthwhile. Again, I have had a high opinion especially of their process chemists so I was surprised that lots of medicinal chemists at other companies were quite angry at them.

    Comment by milkshake — September 7, 2007 @ 9:15 am


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