Get Rich Quick With Old Generic Drugs! The Pyrimethamine Pricing Scandal (2024)

In September, the decision by Turing Pharmaceuticals to increase the price of pyrimethamine, a 62-year-old generic drug used to treat toxoplasmosis and malaria, from approximately $13.50 to $750.00 per pill resulted in a firestorm that ignited social media, led to harsh criticism by 2 Democratic presidential candidates, and was the subject of a satirical monologue by Bill Maher. Walter Palmer, the dentist who killed Cecil the lion in Zimbabwe, must have breathed a sigh of relief as he watched Turing Pharmaceutical's CEO Martin Shkreli replace him as the national villain of the day. After spending several days as the most publically reviled man in the country—a role he seemed to relish—Shkreli was rescued by Pope Francis in true deus ex machina fashion. The Pope's arrival in the United States dominated the media and dampened the intensity of Shkreli's public shaming.

Shkreli, with his “Wolf of Wall Street” smugness, arrogance, and unapologetic greed, made a compelling villain. A former hedge fund manager with a highly checkered past, he now posed as a drug manufacturer and scientific expert. “There are very few people who care about toxoplasmosis more than me,” he said. “I think I know more about toxoplasmosis than anyone in the world.” [1] (Don't tell Jack Remington!)

Shkreli minimized the price increase, grossly underestimating the new cost of treatment for toxoplasmosis by ignoring the fact that it requires not just 6 weeks of high-dose therapy ($94 500), but prolonged maintenance therapy at lower doses [2]. The estimated annual cost—for the pyrimethamine component alone—was closer to $645 500 than the much lower figure cited by Shkreli.

Shkreli justified the 5000% price increase by saying he needed to fund research on toxoplasmosis, although no one had been clamoring for more research on this treatable complication of immunosuppression. It wasn't clear who would be doing this research. Did Turing employ any scientists? Did they have a laboratory? (Of course, there were other expenses beyond pure research. Shortly before the increase went public, I was invited to attend a “launch meeting” in Florida and to join their new Speakers' Bureau, where I would have been taught how to effectively promote their “new” product.) Shkreli also talked about “eradicating” toxoplasmosis, a goal that would presumably require the destruction of the world's livestock and cats.

The implications for the treatment of toxoplasmosis are alarming. Patients with toxoplasmosis usually require hospitalization for seizures or subacute neurologic deficits due to brain lesions and surrounding edema. They are typically started on empiric therapy based on magnetic resonance imaging (MRI) findings, because definitive diagnosis requires brain biopsy. A patient weighing more than 60 kg would need to take 3 25 mg pills per day, at a cost of $15 750 per week, not including the cost of the leucovorin and the sulfadiazine or clindamycin that they would also require. Could hospitals afford to keep pyrimethamine on their shelves to treat the infrequent patient with toxoplasmosis? If not, how long would it take to acquire it from what is now a single supplier for a patient who needed immediate therapy?

Outpatient therapy is even more problematic. Shkreli argued that a “patient assistance program” would prevent patients from paying out of pocket for their treatment. However, it was never made clear how these neurologically impaired patients being discharged from the hospital would access the program. Would they have to remain hospitalized until they had been approved for the assistance program? To what degree would this process prolong hospital stay? Several hospitals have reported unsuccessfully trying to quickly obtain the medication for their uninsured patients, and many physicians have reported being forced to use alternative regimens because of access and affordability issues [3]. These reports cast doubt on Turing's assurances that rapid treatment is available to everyone who needs it.

Although most of the early discussion of this scandal focused on pyrimethamine, Turing, and Shkreli himself, this is far from a new phenomenon. We have recently seen astonishing price increases with other old, generic, and once inexpensive drugs, including nitroprusside, benzathine penicillin, albendazole, albuterol, cycloserine, and doxycycline, to name just a few. In fact, the pre-Turing $13.50 price of pyrimethamine represented a huge but comparatively affordable increase over the $1.00 price before GlaxoSmithKline sold rights to the drug to CorePharma in 2010. Why was it only the recent pyrimethamine price increase that hit social media by storm and that caught the attention of presidential candidates and talk show hosts? Shkreli himself can take much of the credit. He was no faceless, anonymous executive, quietly plotting huge profits in the background. He became an overnight anticelebrity, the bratty face and voice behind the company's aggressive pricing strategy. His own public relations strategy was inconsistent, alternating between feigned compassion for toxoplasmosis sufferers on television and a shameless defense of pure corporate greed on his Twitter feed.

The other reason for the sensation was that pyrimethamine was not an antihypertensive drug or pain medication but a lifesaving drug used by patients with acquired immune deficiency syndrome (AIDS). Shkreli had inadvertently taken on AIDS activists and advocates, who would not just roll over and let this go. It was the press release from the Infectious Diseases Society of America and the HIV Medicine Association (HIVMA), as well as the ubiquitous media presence of HIVMA executive board members, that ignited the controversy. A number of physicians and community groups are continuing the fight by refusing to meet with representatives of a now robust Turing sales force until the price is lowered. It is easier to get people exercised about increasing the price of a drug used to treat disadvantaged AIDS patients than one used to treat congestive heart failure in patients in an intensive care unit.

Shkreli argues that people with uncommon or rare diseases will not get treated unless the drugs to treat their conditions are expensive. That may be true from a drug development standpoint. Drug companies will not develop drugs without the expectation of profit, and profiting from uncommon diseases requires high drug prices. However, in Turing's case, there were no development costs. The drug has existed for over 60 years; profiting from it was merely a matter of seeing the opportunity, purchasing exclusive rights to distribution, then jacking up the price. Shkreli had done this before with a previous company, Retrophin, which bought Thiola, a generic drug for a rare kidney disease, and increased the price by 2000%. He was subsequently ousted from that company for what were euphemistically called “stock irregularities.” Although Shkreli himself may or may not be guilty of breaking the law in his business practices, the sad truth is that in the United States, what Turing has done with pyrimethamine is entirely legal.

The activism surrounding the pyrimethamine price increase has had at least some effect. Turing announced that they will reduce the price of the drug, presumably to a price somewhere between $13.50 and $750.00 per pill. When asked for more specifics regarding price and timing, a Turing representative initially made the following unhelpful statement: “We are committed to lowering the price of Daraprim. To that end, we are working with various stakeholders to ensure we find the right solution, a process which takes time. The right solution will balance the value of the treatment, patient access and affordability.” (written communication with Andrea Weddle. October 11, 2015) A group of concerned physicians and activists representing multiple organizations subsequently met with Turing representatives in early November. They were given no specifics about the company's plans, but they were told that any price reduction was likely to be “modest” (on the order of 10%) [4].

For those in search of happier news, Imprimis Pharmaceuticals, in direct response to the Turing controversy, announced that it would sell a coformulation of pyrimethamine and leucovorin for a dollar per pill. It would be sweet revenge indeed if this product quickly dominated the small pyrimethamine market, completely undercutting all of Turing profits. However, the Imprimis product is not approved by the US Food and Drug Administration, so it is unclear whether it will solve our problem.

I will make 3 predictions about how the Turing pyrimethamine story will play out: (1) The company won't announce the new price for a while, hoping that the controversy will fade away; (2) The new price will remain unacceptably high; and (3) Advocacy groups will refuse to let the issue die. What is harder to predict is whether we will move beyond our transient fascination with a single corporate villain and change our laws so that generic drugs remain as affordable treatments for human disease rather than as investment opportunities for unscrupulous hedge fund managers and Wall Street bankers.

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