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AntifolatesIn useDerivative of an earlier drugNeeds review

Pralatrexate

Also known as Folotyn, 10-propargyl-10-deazaaminopterin

A folate analogue for relapsed or refractory peripheral T-cell lymphoma. The FDA granted accelerated approval in 2009 on response-rate data; the European Medicines Agency refused authorisation in 2012.

From discovery to approval

  1. 1993 · First described

    A 1993 J Med Chem paper reported the synthesis of 10-propargyl-10-deazaaminopterin, which a 2010 review identifies as pralatrexate. In L1210 cells the compound was about five times as potent as methotrexate as a growth inhibitor but about one-third as potent against the enzyme DHFR.[2][3][4][5]

  2. 2009-09-24 · FDA accelerated · 16 years after first description

    Treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). The letter states the application is approved under the accelerated approval regulations (21 CFR 314.510). The 2026 label still carries the accelerated-approval statement; no conversion document was found, and Folotyn is not on FDA's 'Verified Clinical Benefit' accelerated-approval list (opened 26 October 2026).[6]

How it works

Competitively inhibits dihydrofolate reductase and the enzyme folylpolyglutamyl synthetase, which depletes thymidine and other molecules whose synthesis depends on single-carbon transfer.[1]

Where it came from and why

A 2008 review says it was developed to overcome limitations of methotrexate, with better transport into cells and greater polyglutamylation in preclinical studies. A 2013 paper describes a stepwise search from a 10-deaza analogue of aminopterin through edatrexate to pralatrexate.

Cancers

Family and partners

Derived from: Aminopterin

Worth knowing

  • An FDA approval summary says pralatrexate was the first drug approved for relapsed or refractory peripheral T-cell lymphoma, and that accelerated approval was based on a response rate in a single-arm trial; it reports an overall response rate of 27% in 109 evaluable patients (95% CI 19 to 36).[9]
  • PROPEL reports a response rate of 29% (32 of 109 evaluable patients; 12 complete and 20 partial responses) by independent central review, against 27% in the FDA approval summary for the same 109 evaluable patients; the PROPEL abstract does not explain the difference.[7]
  • The CHMP adopted a negative opinion on 19 January 2012 and confirmed it on re-examination on 19 April 2012, citing a single-arm main study with no comparator and no assessment of overall or progression-free survival.[10]
  • The 2026 US label states that the indication is approved under accelerated approval based on overall response rate and that continued approval may depend on a confirmatory trial; its efficacy table lists 29 of 109 evaluable patients (27%) with a response, 9 of them complete or unconfirmed complete.[1]
  • Patients receive vitamin B12 by intramuscular injection and daily folic acid with pralatrexate, according to the FDA approval summary.[9]

References

  1. Acrotech Biopharma Inc. Folotyn (pralatrexate): prescribing information. DailyMed, set ID 9f3d9c4d-9386-4451-b712-0fbdc5478d8f, published 21 September 2026. Read 26 October 2026. Source
  2. DeGraw JI, Colwell WT, Piper JR, Sirotnak FM. Synthesis and antitumor activity of 10-propargyl-10-deazaaminopterin. J Med Chem. 1993;36(15):2228-31. PubMedDOI
  3. Zain J, O'Connor O. Pralatrexate: basic understanding and clinical development. Expert Opin Pharmacother. 2010;11(10):1705-14. PubMedDOI
  4. Molina JR. Pralatrexate, a dihydrofolate reductase inhibitor for the potential treatment of several malignancies. IDrugs. 2008;11(7):508-21. PubMed
  5. Visentin M, Unal ES, Zhao R, Goldman ID. The membrane transport and polyglutamation of pralatrexate: a new-generation dihydrofolate reductase inhibitor. Cancer Chemother Pharmacol. 2013;72(3):597-606. PubMedDOI
  6. U.S. Food and Drug Administration. Approval letter, NDA 022468, Folotyn (pralatrexate injection), Allos Therapeutics, Inc.: accelerated approval, 24 September 2009. Source
  7. O'Connor OA, Pro B, Pinter-Brown L, Bartlett N, Popplewell L, Coiffier B, et al. Pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma: results from the pivotal PROPEL study. J Clin Oncol. 2011;29(9):1182-9. PubMedDOI
  8. Krug LM, Azzoli CG, Kris MG, Miller VA, Khokhar NZ, Tong W, et al. 10-propargyl-10-deazaaminopterin: an antifolate with activity in patients with previously treated non-small cell lung cancer. Clin Cancer Res. 2003;9(6):2072-8. PubMed
  9. Malik SM, Liu K, Qiang X, Sridhara R, Tang S, McGuinn WD Jr, et al. Folotyn (pralatrexate injection) for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma: U.S. Food and Drug Administration drug approval summary. Clin Cancer Res. 2010;16(20):4921-7. PubMedDOI
  10. European Medicines Agency. Folotyn (pralatrexate): refusal of marketing authorisation; CHMP negative opinion 19 January 2012, confirmed on re-examination on 19 April 2012 (Questions and answers EMA/CHMP/255106/2012). Page read 26 October 2026. Source
  11. U.S. Food and Drug Administration. Drugs@FDA: Approval date(s) and history, letters, labels, reviews for NDA 022468 (pralatrexate; Folotyn). Page read 2026-10-26. Source