A survey of breakthrough therapy designations

Journal name:
Nature Biotechnology
Year published:
Published online

As of last month, 41 products have been granted breakthrough therapy designations by the US Food and Drug Administration—drugs against cancer, hepatitis C and monogenetic diseases predominate.

At a glance


  1. Number of BTDs applied for, and number of BTDs granted and denied by CBER and CDER from July 9, 2012 to March 7, 2014.
    Figure 1: Number of BTDs applied for, and number of BTDs granted and denied by CBER and CDER from July 9, 2012 to March 7, 2014.

    See Supp. Fig. 1.

  2. BTDs by category of therapeutics or disease.
    Figure 2: BTDs by category of therapeutics or disease.


  1. Sherman, R.E., Li, J., Shapley, S., Robb, M. & Woodcock, J. Expediting drug development—the FDA's new “breakthrough therapy” designation. N. Engl. J. Med. 369, 18771880 (2013).
  2. Senior, M. Drugs with breakthrough status charm investors. Nat. Biotechnol. 31, 945947 (2013).
  3. IMS Health. Total unaudited and audited global pharmaceutical market by region; 2012–2017 http://www.imshealth.com/deployedfiles/imshealth/Global/Content/Corporate/Press%20Room/Total_World_Pharma_Market_Topline_metrics_2012-17_regions.pdf (2013).
  4. Aggarwal, R.S. What's fueling the biotech engine—2012 to 2013. Nat. Biotechnol. 32, 3239 (2014).
  5. Aggarwal, S.R. What's fueling the biotech engine—2011 to 2012. Nat. Biotechnol. 30, 11911197 (2012).
  6. Aggarwal, S. Targeted cancer therapies. Nat. Rev. Drug Discov. 9, 427428 (2010).
  7. Beers, S.A., Chan, C.H., French, R.R., Cragg, M.S. & Glennie, M.J. CD20 as a target for therapeutic type I and II monoclonal antibodies. Semin. Hematol. 47, 107114 (2010).
  8. Hornberger, J. et al. Cost-effectiveness of adding rituximab to fludarabine and cyclophosphamide for the treatment of previously untreated chronic lymphocytic leukemia. Leuk. Lymphoma 53, 225234 (2012).
  9. D'Cruz, O.J. & Uckun, F.M. Novel Bruton's tyrosine kinase inhibitors currently in development. Onco Targets Ther. 6, 161176 (2013).
  10. Pollack, A. Imbruvica, drug to treat blood cancer, gains FDA approval. The New York Times http://www.nytimes.com/2013/11/14/business/drug-to-treat-blood-cancer-gains-fda-approval.html?_r=0 (13 November 2013).
  11. Chustecka, Z. Ibrutinib (Imbruvica) approved for CLL in US. Medscape Multispecialty. http://www.medscape.com/viewarticle/820537 (13 February 2014).
  12. Lowery, M. Sovaldi approved to treat chronic hepatitis C. Drug Topics http://drugtopics.modernmedicine.com/drug-topics/news/sovaldi-approved-treat-chronic-hepatitis-c?page=full (9 December 2013).
  13. Hillman, P. et al. Ofatumumab + chlorambucil versus chlorambucil alone in patients with untreated chronic lymphocytic leukemia: results of the phase 3 study complement 1. Oral presentation, 55th Annual Meeting of the American Society of Hematology, New Orleans (9 December 2013).
  14. Finn, R. Results of a randomized phase 2 study of PD 0332991, a cyclin-dependent kinase (CDK) 4/6 inhibitor, in combination with letrozole vs letrozole alone for first-line treatment of ER+/HER2- advanced breast cancer (BC). Abstract. Publication Number S1–6. San Antonio Breast Cancer Symposium, San Antonio, Texas (9 December 2013).
  15. Yardley, D.A. et al. Randomized phase II, double-blind, placebo-controlled study of exemestane with or without entinostat in postmenopausal women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on treatment with a nonsteroidal aromatase inhibitor. J. Clin. Oncol. 31, 21282135 (2013).
  16. Shaw, A. et al. Clinical activity of the ALK inhibitor LDK378 in advanced, ALK-positive NSCLC. J. Clin. Oncol. 31, Abstract 8010 (2013).
  17. Döhner, H. Phase I/II study of volasertib (BI 6727), an intravenous Polo-like kinase (Plk) inhibitor, in patients with acute myeloid leukemia (AML): results from the randomized phase II part for volasertib in combination with low-dose cytarabine (LDAC) versus LDAC monotherapy in patients with previously untreated AML ineligible for intensive treatment. Oral presentation at ASH Annual Meeting and Exposition, New Orleans. (8–11 December 2012).
  18. Eisai, Inc. FDA ODAC Briefing Document. Dacogen http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/
    (9 February 2012).
  19. Fellner, C. Ipilimumab (Yervoy) prolongs survival in advanced melanoma. Pharm. Ther. 37, 503511 (2012).
  20. Kuznar, W. Ibrutinib induces rapid durable responses in Waldenströms macroglobulinemia, http://www.onclive.com/conference-coverage/ash-2013/Ibrutinib-Induces-Rapid-Durable-Responses-in-Waldenstrms-Macroglobulinemia.
  21. National Institute for Health Service. Asfotase alfa for hypophosphatasia. http://www.hsc.nihr.ac.uk/topics/asfotase-alfa-for-hypophosphatasia/ (6 December 2013).
  22. Whyte, M.P. et al. Enzyme-replacement therapy in life-threatening hypophosphatasia. N. Engl. J. Med. 366, 904913 (2012).
  23. GlaxoSmithKline. GSK and Prosensa announce primary endpoint not met in Phase III study of drisapersen in patients with Duchenne Muscular Dystrophy. http://www.gsk.com/media/press-releases/2013/gsk-and-prosensa-announce-primary-endpoint-not-met-in-phase-iii-.html (20 September 2013).
  24. Goemans, N.M. et al. Systemic administration of PRO051 in Duchenne's Muscular Dystrophy. N. Engl. J. Med. 364, 15131522 (2011).
  25. Whitely, C.B. et al. Long term effect of sebelipase alfa in patients with liposomal acid lipase (LAL) deficiency. North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Annual Meeting, Abstract No 32 (Chicago, October 10–12, 2013).
  26. Scioderm, Inc. receives positive opinion from European orphan medicinal products committee for novel topical therapy to treat epidermolysis bullosa, Scioderm, 17 December 2013.
  27. Mitchell, A.E., Colvin, H.M. & Palmer Beasley, R. Institute of Medicine recommendations for the prevention and control of hepatitis B and C. Hepatology 51, 729733 (2010).
  28. Ghany, M.G., Strader, D.B., Thomas, D.L. & Seeff, L.B. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 49, 13351374 (2009).
  29. Chen, J. et al. Earlier sustained virologic response end points for regulatory approval and dose selection of hepatitis C therapies. Gastroenterology 144, 14501455 (2013).
  30. Everson, G.T. et al. Efficacy of an interferon and ribavirin-free regimen of daclatasvir, asunaprevir, and BMS-791325 in treatment-naive patients with HCV genotype 1 infection. Gastroenterology 146, 420429 (2014).
  31. Chayama, K. et al. Dual therapy with the nonstructural protein 5A inhibitor, daclatasvir, and the nonstructural protein 3 protease inhibitor, asunaprevir, in hepatitis C virus genotype 1b-infected null responders. Hepatology 55, 742748 (2012).
  32. Kowdley, K.V. et al. Phase 2b trial of interferon-free therapy for hepatitis c virus genotype 1. N. Engl. J. Med. 370, 222232 (2014).
  33. Lawitz, E. et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet 383, 515523 (2014).
  34. Lawitz, E. et al. High efficacy and safety of the all-oral combination regimen, MK-5172/MK-8742 +/- RBV for 12 weeks in HCV genotype 1 infected patients: the C-WORTHY study. 64th Annual Meeting of the American Association for the Study of Liver diseases, Washington, DC; abstract 76 36 (1–5 November 2013).
  35. Merck announces presentation of interim data from study of investigational combination of HCV therapies MK-5172 and MK-8742 at the 2013 American Association for the Study of Liver Diseases (AASLD) Annual Meeting. http://www.mercknewsroom.com/news-release/research-and-development-news/merck-announces-presentation-interim-data-study-investiga (2 November 2013).
  36. Final data from phase 2 combination study of VX-809 and KALYDECO (ivacaftor) showed statistically significant improvements in lung function in people with cystic fibrosis who have two copies of the F508del mutation. http://investors.vrtx.com/releasedetail.cfm?releaseid=687394
  37. Collins, T.R., And a monoclonal antibody treatment helps with muscle volume in sIBM. Neurology Today 13, 3435 (2013).
  38. BioMarin initiates phase 3 trial for amifampridine phosphate for the treatment of LEMS http://www.prnewswire.com/news-releases/biomarin-initiates-phase-3-trial-for-amifampridine-phosphate-for-the-treatment-of-lems-123331068.html (7 June 2011).
  39. Portola pharmaceuticals announces new phase 2 results confirming immediate, dose-dependent and well-tolerated reversal of anticoagulation activity of XARELTO(R) (rivaroxaban) with andexanet alfa (PRT4445*), investigational Factor Xa inhibitor reversal agent. http://investors.portola.com/phoenix.zhtml?c=198136&p=irol-newsroomArticle&ID=1883157&highlight= (9 December 2013)
  40. Desmond, R. et al. Eltrombopag restores tri-lineage hematopoiesis in refractory severe aplastic anemia which can be sustained on discontinuation of drug. Blood doi:doi:10.1182/blood-2013-10-534743 (17 December 2013).
  41. Filippatos, G. et al. Serelaxin in acute heart failure patients with preserved left ventricular ejection fraction: results from the RELAX-AHF trial. Eur. Heart J. doi:doi:10.1093/eurheartj/eht497 (6 December 2013).
  42. European Medicines Agency. Refusal of the marketing authorization for Readanz http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_-_Initial_authorisation/human/002817/WC500160088.pdf (21 February 2014).
  43. Llanos-Cuentas, A. et al. Tafenoquine plus chloroquine for the treatment and relapse prevention of Plasmodium vivax malaria (DETECTIVE): a multicentre, double-blind, randomised, phase 2b dose-selection study. Lancet doi:10.1016/S0140-6736(13)62568-4 (19 December 2013).

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  1. Saurabh (Rob) Aggarwal is at Novel Health Strategies LLC, Bethesda, Maryland, USA, and the Institute for Global Policy Research, Washington, DC, USA.

    • Saurabh (Rob) Aggarwal

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