I hate to be that person, I always feel exactly like the xkcd cartoon I referenced in the title. However, when somebody posts on the internet and it’s not so much an article as a display of stunning ignorance the scientist in me gets offended and needs to correct.
The post that pissed me off is at io9, which can generally be relied upon for good science fiction news with the occasional interesting real science mixed in. The post “Three Sleazy Moves Pharmaceutical Companies Use to Extend Patents,” however, is a hatchet job. You may be able to detect this from the title, which indicates the author may not be objective on the subject. I understand that people are upset that prescription drugs cost a lot (see my post further down about how my rosacea meds cost $350 a month) and that pharmaceutical companies have done some things which make them seem sort of evil. Full disclosure: I work for Eli Lilly and Company.* My paycheck comes from a large pharmaceutical company. You should, however, view what follows as an objective response to the author from someone who has direct and relevant experience, not as a defense of the industry that puts food on my table.
OK, so now that’s out of the way, let’s visit the author’s three “sleazy” things Big Pharma does:
1) The Mashup
The argument here is that combination drugs, like Caduet (containing the active drugs Norvasc and Lipitor) are a scam to extend the patent on one of the drugs which is coming off patent by mixing with one still on patent. In this way Caduet (sold beginning in 2004) effectively extended Pfizer’s patent on Norvasc (expiring in 2007) by combining it with Lipitor (scheduled to expire in 2011) or, possibly, vice versa. The only problem with this argument is that a) Norvasc still expired in 2007 and generic versions of amlodipine went on sale almost immediately and b) Lipitor went off patent as originally scheduled in 2011 and generic versions of atorvastatin were approved for sale that day. Neither’s patent was extended by Caduet. Yes, from the time period from 2007-2011 you could not buy a generic version of a pill containing both amlodipine and Lipitor because the Lipitor bit was still on patent. You could, however, buy generic amlodipine and Pfizer’s Lipitor if you really wanted to take both and save some money.
By the way, Caduet went generic on Nov. 30th 2011, the same day Lipitor did.
2) The Planned Purification
The argument here is that a “purer” version (Lexapro) of the existing drug Celexa was specifically developed to lengthen the patent exclusivity for Celexa, scheduled to go off patent in 2006. This is correct, but not for the reason the author states.
It is true that Lexapro does not go off-patent until 2012; it is not true that, “this purified version instantly becomes a new drug in the eyes of the FDA, warranting a five year period of exclusivity as a new chemical entity”.
Let’s step back a bit. In chemical synthesis a carbon atom has four other atoms covalently bonded to it. These occupy places in space 109° apart … sort of like the points of a triangular pyramid with the carbon in the center. In most reactions, the site of addition is random. Imagine your body. You decide to add on an extra arm, but you don’t get to choose whether it goes on the right side of your body or the left. Half the time you end up with two arms on the left side. If the opposite happens you have two right arms. The two results are mirror images. This is equivalent to the (R) and (S) isomers that result from a chemical synthesis (rectus and sinister, right and left).
In pharmacology often only one of the two is active. The other is frequently less active or has adverse effects. In the case of the molecule citalopram, the (S) isomer is active and the (R) isomer is inactive; at some point during development the developer discovered this. Celexa was a 1:1 mixture of the two. Lexapro is the (S) isomer only. There is some evidence that the presence of the (R) isomer inhibits binding of the (S) isomer to the serotonin receptor.
The benefit the sponsor received from the FDA was that they could use all the clinical trial data from Celexa to help demonstrate Lexapro’s safety. It only took Lexapro 3.5 years to make it through the safety/efficacy process because the manufacturer already had loads of data before they stared the process for regulatory approval. The FDA approved it in 2002.
They also, completely contrary to the author’s statement, approved a generic version less than four years later in 2006. Exclusivity was granted by the U.S. Patent and Trademark Office on the new process used in its manufacture which yields only the (S) isomer instead of a mixture of both isomers. As a result, Lexapro doses are 5, 10, and 20 mg versus the Celexa doses of 20 mg or 40 mg (which are actually 10 mg (R)-citalopram and 10 mg (S)-citalopram, etc). The potential benefit of Lexapro is that you’re not also getting an equal dose of the inactive compound, and exposed to its potential side effects, at the same time. Thus the author’s statement, “One possible benefit of the purification route is a decrease in side effects associated with the molecule. Users of Lexapro only need to take half the dosage of Celexa, leading many to correlate a decrease in side effects with Lexapro,” is disingenuous because patients are taking exactly the same dose of the active compound and they really might be seeing decreased side effects because they’re not taking the inactive version on top of the active.
3) Alternate Delivery
The author argues using an example of Intermezzo, which contains the same active ingredient as Ambien, which was approved by the FDA “as a new chemical entity in 2011” by changing the dosage form. This is also inaccurate, Transept Pharmaceuticals (not the original patent holder on zolpidem, that was Sanofi-Aventis) was granted a new indication which uses the new dosage form. They had to fund a new clinical trial for this, so it’s not like they didn’t invest significant time and money. The alternative is just to allow people to prescribe any drug for anything they want to, which might be cheaper but is definitely not safer.
So, please, I recognize that prescription medication is expensive. But there is a difference between protecting your intellectual property and being evil. Nobody I work with is evil, we take our patients’ safety very seriously. But, at the same time, it’s a business and businesses have to make a profit. That isn’t necessarily evil.
*The views expressed in this post are the personal opinion of the author and do not reflect those of Eli Lilly and Company.