The Drug
Daraprim is the brand name for pyrimethamine, an antiparasitic drug the FDA approved in 1953. It is the standard treatment for toxoplasmosis, an infection caused by Toxoplasma gondii that can be fatal in people with weakened immune systems. No equally effective alternative has been approved since.
| Fact | Detail |
|---|---|
| Generic name | Pyrimethamine |
| Drug class | Antiparasitic / folic acid antagonist |
| FDA approved | 1953 |
| Formulation | 25 mg oral tablets |
| Standard use | Treatment of toxoplasmosis |
| Current status | Available as brand (Daraprim) and multiple generics since 2020 |
Development
Gertrude Elion and George Hitchings developed pyrimethamine at Burroughs Wellcome in London. Instead of screening compounds at random, they studied the biochemical differences between parasite cells and human cells, then designed a drug to exploit them. Their work in rational drug design contributed to the 1988 Nobel Prize in Physiology or Medicine.
Pyrimethamine was originally approved for toxoplasmosis and malaria. In August 2017, the CDC removed the malaria indication because parasite resistance and better alternatives had made it ineffective for that use. Toxoplasmosis remains its only approved indication.
How It Works
Pyrimethamine blocks dihydrofolate reductase, or DHFR, inside the parasite. DHFR is required for DNA synthesis. Without it, the parasite cannot replicate.
Parasite DHFR binds pyrimethamine much more tightly than human DHFR. Doses that kill the parasite therefore have limited effect on human cells. At the higher doses used for toxoplasmosis, some bone marrow suppression can still occur, so physicians always give leucovorin (folinic acid) alongside it.
Standard treatment combines pyrimethamine with sulfadiazine, which blocks an earlier step in the same folate pathway. Blocking two sequential steps produces a stronger antiparasitic effect. Leucovorin protects the patient's bone marrow without reducing the drug's effect on the parasite.
Who Needs It
HIV/AIDS patients are the largest affected group. When CD4+ T-cell counts fall below 100 to 200 cells per microlitre, dormant Toxoplasma cysts in the brain can reactivate. Toxoplasmic encephalitis was historically the most common cause of focal brain lesions in AIDS patients. About 30% of seropositive AIDS patients develop reactivation disease without prophylaxis.
Organ transplant recipients risk reactivation because immunosuppressive drugs can allow dormant cysts to reactivate.
Cancer patients on chemotherapy risk reactivation during treatment-induced immunosuppression.
Newborns with congenital toxoplasmosis may need up to one year of continuous treatment with pyrimethamine, sulfadiazine, and leucovorin. Without treatment, the infection can cause blindness and permanent neurological damage.
Pregnant women with acute infection are treated to reduce transmission risk from about 45% to 9%.
Pricing History
| Period | Owner | Price per tablet |
|---|---|---|
| 1953 to ~2010 | Burroughs Wellcome, then GlaxoSmithKline | ~$1.00 |
| ~2010 to 2014 | CorePharma (via RoundTable Healthcare Partners) | $1.00 to $1.50 |
| 2014 to August 2015 | Amedra/Impax Laboratories | $13.50 |
| August 2015 onward | Turing Pharmaceuticals (later Vyera) | $750.00 |
Daraprim cost about $1 per tablet from 1953 through 2010. In March 2015, Impax Laboratories acquired the CorePharma portfolio for $700 million. On August 10, 2015, Turing bought the Daraprim rights from Impax for $55 million. Within weeks, Turing raised the price to $750.
In November 2015, Turing introduced a hospital discount program at $375 per pill and a 340B program at lower rates. The list price stayed at $750.
Generic Availability
The FDA approved the first generic pyrimethamine on February 26, 2020. Cerovene, Inc. manufactured it. Multiple companies now make the drug:
- Cerovene (first approval, February 2020)
- Dr. Reddy's Laboratories
- Oakrum Pharma (approved March 2020)
- Teva Pharmaceuticals USA
- Alvogen Inc.
- Fera Pharmaceuticals
- NorthStar Rx LLC
Generic entry was delayed by about five years. In its 2020 complaint, the FTC documented practices it described as anticompetitive: restricted distribution that blocked generic manufacturers from getting samples for bioequivalence testing, exclusive agreements with the sole approved supplier of the raw ingredient, and data restrictions that obscured market size.