To nurture a drug through the tortuous process of drug approval is an extraordinarily expensive business. For a pharmaceutical company to gain a return on an investment of many millions, it needs to ensure that the drug will have a broad use among a potentially huge patient body.
There are two possible strategies for guaranteeing the numbers. The first is to develop the modern equivalent of a liver pill, an all-purpose cure-all that can be applied to chronic symptoms of every description. Another good strategy is to seize upon a newly defined illness with vague enough symptoms to apply to just about anybody.
Both these strategies may be part of Pfizer’s long-term game plan for Lyrica (pregabalin). The drug was originally approved by the US Food and Drug Administration in 2004 for a highly specific condition: neuropathic (nerve) pain—nerve damage as a result of diabetes or as a complication of shingles (post-herpatic neuropathy, or PHN).
This condition alone represents a sizable market niche; half of the USA’s 18 million diabetics will develop excruciating burning or stabbing pain in the extremities, and 150,000 patients have PHN.
Approval in the UK and elsewhere followed shortly.
Pfizer then decided the new kid on the block might also be able to be used as an adjunctive (chaser) drug to treat partial onset seizures, for which the company received approval in the USA in 2005.
This new indication no doubt stemmed from the great success of their epilepsy drug Neurontin (gabapentin), which Pfizer later discovered could also be used to treat diabetic neuropathy.
Pfizer moved on to a highly lucrative growth market in the form of a mental condition called ‘generalized anxiety disorder (GAD)’, characterized by ‘depressive symptoms and panic, headaches and muscle aches’.
This ‘disorder’, claimed Pfizer, afflicts some two million patients, or 5 per cent of the population at some point in their lives.
If you don’t yet see the connection between Lyrica’s various indications, Pfizer certainly did. Mental symptoms like GAD, claims the company, are far more common with people with chronic medical conditions. People who live with chronic pain or who are wondering if they’re about to have a fit are, not surprisingly, anxious.
Within two years, Pfizer received approval for Lyrica to be used to treat GAD in the European Union.
The drug, an alpha-2-delta ligand, is believed to work by ‘calming hyper-excited neurons’. It appears to bind to a subunit of the calcium channels in the central nervous system and to calm pain receptors and seizures in animal models. When studied in the test tube, it appeared to release several neurotransmitters. Pfizer doesn’t understand its mechanism of action. This, in other words, is a neurochemical looking for a disease.
Although Pfizer conducted studies on more than 9000 patients, adverse events were ‘moderate’. The most common side effects include dizziness (in 29 per cent of patients), sleepiness (22 per cent) and a number of visual disturbances, such as blurred vision (6 per cent), a lack of visual acuity (7 per cent) and visual field changes (13 per cent) (Lyrica manufacturer’s information).
Rats given the drug and studied over their lifetimes developed ocular lesions, including atrophy of the retina and loss of photoreceptor cells and corneal inflammations.
Another side effect of Lyrica is weight gain; about one in 12 patients gain up to 7 percent or more of their body weight. So, if your social anxiety is bound up with a lack of confidence or a poor self-image, this drug could make you feel worse about yourself.
Diabetics gained an average of 5.2 kg (11.5 pounds) and as much as 16 kg (35 pounds). This is a particular concern for diabetics, since weight gain can often send blood sugar levels spiralling out of control.
Aside from piling on the pounds, some 6 per cent of patients suffer water retention in the extremities. In diabetics, problems of weight gain and water retention escalated (7.5 per cent and 19 per cent, respectively) among patients taking both Lyrica and a thiazolidinedione anti-diabetic drug.
Diabetics should also note that animals given this drug developed skin ulcerations, from erythema or necrosis (skin death), although these effects weren’t observed in human trials.
More worrying, the drug has demonstrated a high incidence of haemangiosarcoma (cancer in the blood vessels) among two strains of mice. What this means, as animal studies don’t always apply to humans, is anyone’s guess.
Besides possibly causing cancer, the drug causes a decrease in blood platelet counts, with 5 per cent of patients suffering a significant decrease. Lowered levels of blood platelets affect the ability of the blood to clot and may precipitate haemorrhage.
Patients who take pregabalin also demonstrate worrying changes in electrocardiogram readings, called a prolongation of the PR interval. This condition is seen in alcoholics after binge drinking (Neth J Med, 2005; 63(2): 59–63) and predisposes to interrupted electrical impulses to heart muscles, arrhythmia and possibly cardiac arrest.
The drug also causes elevations in levels of creatine kinase, an enzyme in the muscles. When muscles are injured this enzyme leaks out into the blood stream. Elevated levels (also commonly caused by statins) are often associated with myopathy, or muscle weakness.
Finally, you might think twice about this drug if you want to have a baby, particularly if you are the male partner. In various animal models, the drug lowered sperm count, increased sperm abnormalities, reduced fertility and caused miscarriages and birth defects. Nevertheless, in the one short-term study carried out in men the drug lowered sperm count, but not to a pronounced degree.
It’s probably not such a good idea to give it to children, either. Young animals given the drug suffered difficulties with motor skills and learning, even after the drug was withdrawn.