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Breakthrough Therapies

What is a Breakthrough Therapy?
A new drug may be designated as a breakthrough therapy by the Food and Drug Administration (FDA) if it is intended to treat a serious or life-threatening disease and preliminary clinical evidence suggests it provides a substantial improvement over existing therapies. Once the breakthrough therapy designation is requested by the drug sponsor, the FDA and sponsor work together to determine the most efficient path forward.


Breakthrough Designations Announced By Companies (Updated 9/5/2014):

  • Kalydeco - (Vertex) - 2 cystic fibrosis designations

    o    in combination with VX-809 in patients with two copies of the F508del mutation 

    o    ​monotherapy for other CFTR mutations (Received FDA approval for eight additional mutations 2/21/2014)

  • Ibrutinib - (J&J/Pharmacyclics) - 3 designations 

    o    mantle cell lymphoma (Received FDA approval 11/13/2013 as Imbruvica)

    o    waldenstrom macroglobulinemia (WM)

    o    chronic lymphocytic leukemia (Received FDA approval 2/12/2014 as Imbruvica, expanded to additional CLL populations 7/28/2014)

  • LDK378 - (Novartis) - ALK+ NSCLC resistant to crizotinib (Received FDA approval 4/29/2013 as Zykadia (ceritinib))
  • Palbociclib - (Pfizer) - treatment of post-menopausal patients with ER+, HER2- locally advanced or metastatic breast cancer
  • Lambrolizumab (later Pembrolizumab) - (Merck) - inoperable and metastatic melanoma (Received FDA approval 9/4/2014 as Keytruda)
  • SD101 - (Scioderm) - topical cream for the treatment of inherited Epidermolysis Bullosa (EB)
  • Daratumumab - (Janssen) - for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), or who are double refractory to a PI and IMiD
  • Daclatasvir*- (Bristol-Myers) - interferon-free treatmemt of Hepatitis C *combination of daclatasvir with two other direct-acting antivirals, asunaprevir, an NS3 protease inhibitor and BMS-791325, an NS5B non-nucleoside polymerase inhibitor
  • ABT-450* - (AbbVie) - interferon-free 3-DAA treatment of Hepatitis C tested both with and without ribavirin *combination of ABT-450 with two other drugs, ABT-267, an NSA5 inhibitor, and ABT-333, a non-nucleoside polymerase inhibitor
  • Gazyva (obinutuzumab) - (Genetech/Roche) - for the treatment of chronic lymphocytic leukemia (CLL) (Received FDA approval 11/1/2013)
  • Sebelipase Alfa - (Synageva) - for the treatment of early onset lysosomal acid lipase deficiency (LAL deficiency)
  • Asfotase Alfa - (Alexion Pharmaceutical) - for the treatment of patients with hypophosphatasia (HPP) whose first signs or symptoms occurred prior to 18 years of age, including perinatal-, infantile-, and juvenile-onset forms of the disease
  • Serelaxin - (Novartis) - for the treatment of acute heart failure
  • Drisapersen - (GlaxoSmithKline) - for the treatment of Duchenne muscular dystrophy (DMD) in ambulant and non-ambulant boys who carry dystrophin gene mutations amenable to exon 51 skipping
  • BYM338 (bimagrumab) - (Novartis) - for the treatment of sporadic inclusion body myositis (sIBM)
  • Sofosbuvir/ledipasvir combination - (Gilead) - for the treatment of Hepatitis C
  • Firdapse (amifampridine phosphate) - (Catalyst Pharmaceutical) - for the symptomatic treatment of Lambert-Eaton Myasthenic Syndrome (LEMS)
  • Entinostat - (Syndax Pharmaceuticals) - in combination with exemestane for the treatment of metastatic ER-positive breast cancer in postmenopausal women who have progressed on hormonal therapy
  • Arzerra (ofatumumab) - (Genmab A/S, GlaxoSmithKline) - in combination with chlorambucil for the treatment of previously untreated chronic lymphocitic leukemia (CLL) in patients for whom fludarabine-based therapy is inappropriate (Received FDA approval 4/17/2014)
  • Volasertib - (Boehringer Ingelheim) - for the treatment of previously untreated acute myeloid leukemia (AML) in patients over the age of 65
  • Alectinib - (Roche) - for the treatment of non-small cell lung cancer
  • MK-5172/MK-8742 - (Merck) - for the treatment of Hepatitis C
  • cPMP - (Alexion) - for the treatment of molybdenum cofactor deficiency (MoCD) type A
  • PRT4445 (andexanet alfa) - (Portola Pharmaceuticals) - a Factor Xa inhibitor antidote
  • Tafenoquine - (GlaxoSmithKline) - for the treatment of Plasmodium vivax malaria
  • Idelalisib - (Gilead) - for the treatment of chronic lymphocitic leukemia (CLL) (Received FDA approval 7/24/2014 as Zydelig)
  • Tafinlar (dabrafenib) - (GlaxoSmithKline) - for the treatment of BRAF V600E mutation-positive non-small cell lung cancer (NSCLC)
  • VX-661/Kalydeco - (Vertex) - in combination for the treatment of cystic fibrosis in  patients with two copies of the F508del mutation
  • Sofosbuvir - (Gilead) - for the treatment of hepatitis C (Received FDA approval 12/6/2013 as Sovaldi)
  • Eltrombopag - (GlaxoSmithKline) - for the treatment of severe aplastic anemia (Received FDA approval 8/26/2014 as Promacta)
  • Daclatasvir/asunaprevir combination - (Bristol-Myers) - for the treatment of genotype 1b hepatitis C
  • Bivalent rLP2086 - (Pfizer) - for the prevention of invasive meningococcal disease caused by Neisseria meningitidis serogroup B in persons 10 – 25 years of age
  • Bexsero - (Novartis) - for the prevention of invasive meningococcal disease caused by Neisseria meningitidis serogroup B
  • Mydicar - (Celladon) - for reducing hospitalizations for heart failure in NYHA class III or IV chronic heart failure patients who are NAb negative
  • AZD9291 - (AstraZeneca) -  for the treatment of patients with metastatic, EGFR T790M mutation-positive, non-small cell lung cancer (NSCLC) whose NSCLC has progressed during treatment with an FDA-approved, EGFR tyrosine kinase inhibitor
  • Nivolumab - (Bristol-Myers) - for the treatment of patients with Hodgkin lymphoma (HL) after failure of autologous stem cell transplant and brentuximab
  • Elotuzumab - (Bristol-Myers) - for use in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma in patients who have received one or more prior therapies
  • CO-1686 - (Clovis Oncology) - for the treatment of second-line EGFR mutant NSCLC in patients with the T790M mutation
  • MPDL3280A - (Roche) - an anti-PD-L1 immunotherapy for people previously treated for metastatic urothelial bladder cancer
  • Arikayce - (Insmed) - for the treatment of treatment-refractory nontuberculous mycobacterial lung disease
  • Idarucizumab - (Boehringer Ingelheim) - a specific antidote for Pradaxa, an anticoagulant
  • Blinatumomab - (Amgen) - for the treatment of acute lymphoblastic leukemia (ALL)
  • CTL019 - (Novartis) - for the treatment acute lymphoblastic leukemia (ALL)
  • Nintedanib - (Boehringer Ingelheim) - for the treatment of idiopathic pulmonary fibrosis (IPF)
  • Pirfenidone - (InterMune) - for the treatment of idiopathic pulmonary fibrosis (IPF)
  • CRS-207 - (Aduro) - in combination with GVAX for the treatment of pancreatic cancer
  • Nuplazid (pimavanserin) - (Acadia) for the treatment of Parkinson's disease psychosis
*As of September 3, 2014, FDA lists 213 total requests for Breakthrough designation, 61 requests granted, and 116 requests denied. FDA does not disclose information regarding specific drugs or sponsors. Currently, about twelve granted requests have not been publicly announced by their sponsors.
Exceptional Early Progress with Breakthrough Therapies:

Working with our partners in all sectors, Friends took ‘Breakthrough’ from concept, to scientific whitepaper, to bipartisan legislative solution, to a tool in full use by FDA to expedite the approval of multiple drugs in 13 months.

On Novemer 1, 2013, only a year after being signed into law, and 29 designations being announced, the first Breakthrough designation recieved full FDA Approval.

Here is a list of 2013's Breakthrough designations and approvals. Twelve of the year's 28 publicly announced designations were for cancer drugs, as well as two of its three Breakthrough approvals.

The Issue:

As knowledge about complex disease such as cancer and HIV/AIDS has expanded, researchers have been able to develop increasingly precise methods of treatment. Targeted therapies, a variety of drugs that targets specific molecular pathways, allow physicians and researchers to identify patients highly likely to respond to treatment. Frequently, these new drugs show major clinical activity and significant improvement over currently available treatment early in their development. In cases where new drugs show so much promise, and particularly in cases where existing treatment options are limited, the traditional multi-phase, sequential drug development process may not be appropriate.

Our Work Toward a Solution for Patients:
On November 10, 2011, Friends of Cancer Research and the Engelberg Center for Healthcare Reform at Brookings co-hosted the fourth-annual Conference on Clinical Cancer Research, an event which brings together experts in cancer drug development from academia, industry, federal health and regulatory agencies, and patient advocacy. A panel from this conference discussed potential approaches to speed the FDA approval process for drugs that show large treatment effects early in development while still ensuring drug safety and efficacy.
Creating Bipartisan Legislative Action:
The "Advancing Breakthrough Therapies for Patients Act" was introduced in the Senate by Senators Bennet (D-CO), Hatch (R-UT), and Burr (R-NC) on March 26, 2012. Two months later, Congresswoman DeGette (D-CO) and Congressman Bilbray (R-CA) introduced the “Breakthrough Therapy Act” in the House of Representatives. The bills received bipartisan support, and were included as an amendment to the Food and Drug Administration Safety and Innovation Act, the latest iteration of the Prescription Drug User Fee bill. On July 9, 2012, the breakthrough therapy designation was signed into law.
A new drug may be designated as a breakthrough therapy if it is intended to treat a serious or life-threatening disease and preliminary clinical evidence suggests it provides a substantial improvement over existing therapies. Once the breakthrough therapy designation is requested by the drug sponsor, the FDA and sponsor work together to determine the most efficient path forward. The legislation mandates FDA guidance be developed outlining the criteria and process for the breakthrough therapy designation.
At the 2012 Conference, Friends developed a white paper and panel discussion in the pursuit of encouraging use of the new pathway and informing FDA guidance.


Breakthrough Therapy (and Friends) in the News