When Generics Arrived
The FDA approved the first generic pyrimethamine on February 26, 2020. Cerovene, Inc. made it. The approval came four and a half years after Turing Pharmaceuticals raised the price of Daraprim from $13.50 to $750 per pill. An ANDA (Abbreviated New Drug Application) for generic pyrimethamine had been filed by 2014. Daraprim's patent had expired decades earlier. The FTC's 2020 complaint said anticompetitive practices caused the five-year delay.
Why It Took Five Years
Daraprim faced no patent barrier to generic entry. Vyera Pharmaceuticals used three strategies described in the FTC's 2020 antitrust complaint:
Restricted distribution. Vyera sold Daraprim only through Walgreens Specialty Pharmacy under agreements that barred sales to generic manufacturers. Generic companies need branded drug samples for the bioequivalence testing the FDA requires for approval. Multiple manufacturers spent more than a year trying to buy Daraprim samples and failed. At least one dropped its generic program.
Exclusive API supply agreements. Vyera locked up Fukuzyu Pharmaceutical Co., Ltd., the only FDA-approved manufacturer of the pyrimethamine active ingredient for the US market. The exclusive contract barred Fukuzyu from supplying competitors. Vyera also paid RL Fine Chem about $10 million to sign an exclusive agreement, even though it never bought any product from RL Fine. Vyera received no supply from either company. According to the FTC complaint, the contracts existed only to block competitors from the raw material.
Data blocking. Vyera stopped distributors from selling Daraprim sales data to reporting companies such as IQVIA. Generic companies use that data to estimate market size before deciding whether to enter the market.
The FTC estimated that these practices delayed generic entry by about five years and generated $64 million in monopoly profits.
Current Manufacturers
As of 2024, multiple companies make generic pyrimethamine tablets (25 mg):
| Manufacturer | Notes |
|---|---|
| Cerovene, Inc. | First generic approved, February 26, 2020 |
| Dr. Reddy's Laboratories | Commercial partner with Cerovene |
| Oakrum Pharma | Approved March 13, 2020 |
| Teva Pharmaceuticals USA | Major generics manufacturer |
| Alvogen Inc. | |
| Fera Pharmaceuticals | |
| NorthStar Rx LLC | Marketing start October 1, 2024 |
The FTC settlement required Vyera to license Daraprim to any qualified generic manufacturer that asked for it. Vyera also had to end its exclusive supply agreements and distribution restrictions.
Current Pricing
Generic pyrimethamine tablets sell for roughly $20 to $30 per pill through retail pharmacies, depending on the supplier. Prices have not returned to the pre-2015 level of $13.50 or the pre-2010 level of about $1. The FTC settlement required Vyera to provide Daraprim at no more than $1 per tablet to certain buyers.
The CREATES Act
The CREATES Act (Creating and Restoring Equal Access to Equivalent Samples) became law in December 2019 as part of a spending bill. It lets generic manufacturers bring a civil action in federal court if they are denied the branded drug samples they need for bioequivalence testing.
The law passed more than four years after the Daraprim price hike and after the 2016 congressional hearings documented the blocked-sample strategy in detail.
The Compounding Alternative
Before generics reached the market, Imprimis Pharmaceuticals, a compounding pharmacy in San Diego, offered a compounded version of pyrimethamine and leucovorin for $99 per 100 capsules. Imprimis announced the alternative in October 2015, one month after the Daraprim price increase drew national media coverage.
Compounded drugs are prepared by pharmacies for individual prescriptions and do not go through the standard FDA approval process. Insurers and hospitals did not always accept them, so many patients who needed reliable coverage could not use the Imprimis product.
Timeline
| Date | Event |
|---|---|
| 1953 | Pyrimethamine (Daraprim) approved by FDA |
| 2014 | First ANDA filed for generic pyrimethamine |
| August 2015 | Turing acquires Daraprim, raises price to $750 |
| October 2015 | Imprimis offers compounded alternative at $99/100 capsules |
| September 2017 | Turing rebrands as Vyera; anticompetitive practices continue |
| December 2019 | CREATES Act signed into law |
| January 27, 2020 | FTC files antitrust complaint |
| February 26, 2020 | First generic pyrimethamine approved (Cerovene) |
| March 13, 2020 | Oakrum Pharma generic approved |
| December 2021 | FTC settlement requires $1/tablet provision and generic licensing |
| May 2023 | Vyera files Chapter 11 bankruptcy |