FDA "Breakthrough Therapy" Designations

A list of publicly-announced breakthrough therapy designations granted by the FDA.

Breakthrough status was introduced in the 2012 FDA Safety and Innovation Act to expedite development and review of a potential new medicine intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition, when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. Below is a list of publicly announced breakthrough therapy designations for products or indications not yet approved. For regular tracking of breakthrough designations, see our sister publication Pharmaceutical Approvals Monthly.

Company	Product(s)	Indication
AbbVie	Triple direct-acting antiviral combination of the protease inhibitor ABT-450 boosted with ritonavir, the NS5A inhibitor ABT-267, and the non-nucleoside polymerase inhibitor ABT-333	Chronic hepatitis C
Acadia	Nuplazid (pimavanserin), a selective serotonin inverse agonist	Parkinson’s psychosis
Aduro BioTech	Combination immunotherapy comprising CRS-207 (based on a live-attenuated, double-deleted Listeria monocytogenes immunotherapy platform) and GVAX Pancreas vaccine	Pancreatic cancer
Alexion	Asfotase alfa, a recombinant protein that addresses the underlying cause of hypophosphatasia by targeting replacement of the missing enzyme	Hypophosphatasia patients whose first signs or symptoms occurred prior to 18 years of age
Alexion	Cyclic pyranopterin monophosphate (cPMP, or ALXN1101), an enzyme co-factor replacement therapy	Molybdenum cofactor deficiency type A
Ariad	AP26113, oral inhibitor of anaplastic lymphoma kinase	ALK+ metastatic non-small cell lung cancer in patients who are resistant to crizotinib
AstraZeneca	AZD9291, third-generation EGFR inhibitor	Metastatic EGFR T790M mutation-positive non-small cell lung cancer that has progressed during treatment with an FDA-approved EGFR tyrosine kinase inhibitor
Boehringer Ingelheim	Idarucizumab, a humanized antibody fragment	Antidote for the oral anticoagulant Pradaxa (dabigatran)
Boehringer Ingelheim	Volasertib, a selective and potent polo-like kinase inhibitor	Untreated acute myeloid leukemia in patients ineligible for intensive therapy, in combination with low-dose cytarabine
Bristol-Myers Squibb	Opdivo (nivolumab), a fully human PD-1 immune checkpoint inhibitor	Hodgkins lymphoma after failure of autologous stem cell transplant and brentuximab
		Previously treated advanced melanoma
Bristol-Myers Squibb	Daclatasvir, an NS5A replication complex inhibitor, and asunaprevir, an NS3 protease inhibitor	Genotype 1b chronic hepatitis C infection (Withdrawal of asunaprevir NDA announced Oct. 7, 2014; “complete response” letter for daclatasvir NDA announced Nov. 26, 2014
Bristol-Myers Squibb	Triple direct-acting antiviral combination of the NS5A replication complex inhibitor daclatasvir, NS3 protease inhibitor asunaprevir, and NS5B non-nucleoside polymerase inhibitor BMS-791325	Chronic hepatitis C
Bristol-Myers Squibb/AbbVie	Elotuzumab, a humanized monoclonal antibody targeted against Signaling Lymphocyte Activation Molecule (SLAMF7, also called CS1)	Used in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma in patients who have received one or more prior therapies
Catalyst Pharmaceutical Partners	Amifampridine phosphate	Symptomatic treatment of patients with Lambert-Eaton myasthenic syndrome
Celladon	Mydicar, a genetic enzyme replacement therapy to correct the deficiency in the enzyme SERCA2a in heart failure patients	Reducing hospitalizations for heart failure in NYHA class III or IV chronic heart failure patients who are Nab-negative
Clovis Oncology	CO-1686, an oral, targeted covalent (irreversible) inhibitor of mutant forms of the epidermal growth factor receptor	Monotherapy for treatment of second-line EGFR mutant NSCLC in patients with the T790M mutation
Genmab/J&J	Anti-CD38 antibody daratumumab	Multiple myeloma patients who have received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent or who are double refractory to such drugs
GlaxoSmithKline	Tafinlar (dabrafenib), BRAF inhibitor	Treatment of patients with metastatic BRAF V600E mutation-positive NSCLC who have received at least one prior line of platinum-containing chemotherapy
GlaxoSmithKline/Medicines for Malaria Venture	Tafenoquine, an 8-aminoquinoline derivative	Treatment and relapse prevention of Plasmodium vivax malaria
Insmed	Arikayce (liposomal amikacin for inhalation)	Nontuberculous mycobacterial lung disease in adults who are treatment refractory
Janssen/Pharmacyclics	Imbruvica (ibrutinib), a Bruton’s kinase inhibitor	Waldenstrom's macroglobulinemia
Juno Therapeutics/Memorial Sloan Kettering Cancer Center	JCAR015, a chimeric antigen receptor	Relapsed or refractory B-cell acute lymphoblastic leukemia
Merck	All-oral combination regimen comprising MK-5172, an HCV NS3/4A protease inhibitor, and MK-8742, an HCV NS5A replication complex inhibitor	Chronic hepatitis C
Merck	Keytruda (pembrolizumab), a PD-1 inhibitor	Treatment of patients with EGFR mutation-negative and ALK rearrangement-negative NSCLC whose disease has progressed on or following platinum-based chemotherapy
Neurocrine Biosciences	NBI-98854, a vesicular monoamine transporter 2 inhibitor	Tardive dyskinesia
Novartis	Bexsero (meningococcal group B vaccine [rDNA, component, adsorbed])	Prevention of invasive meningococcal disease caused by serogroup B
Novartis	Bimagrumab (BYM338), a fully human monoclonal antibody	Sporadic inclusion body myositis
Novartis	Serelaxin (RLX030), a recombinant form of the hormone human relaxin-2	Acute heart failure (“Complete response” letter announced May 16, 2014)
Novartis/University of Pennsylvania	CTL019, personalized chimeric antigen receptor (CAR) T-cell therapy	Relapsed and refractory adult and pediatric patients with acute lymphoblastic leukemia
Pfizer	Palbociclib (PD-0332991), a cyclin-dependent kinases 4 and 6 inhibitor	Post-menopausal women with ER+, HER2 locally advanced or metastatic breast cancer
Portola	Andexanet alfa, a Factor Xa inhibitor antidote	Reversal of Factor Xa inhibitor anticoagulant activity
Prosensa (GlaxoSmithKline returned development rights to Prosensa in January 2014)	Drisapersen (formerly GSK2402968/PRO051), an antisense oligonucleotide	Duchenne muscular dystrophy in boys with dystrophin gene mutations amenable to an exon 51 skip
Regeneron	Eylea (aflibercept), a fusion protein designed to bind to multiple isoforms of vascular endothelial growth factor-A and placental growth factor	Treatment of diabetic retinopathy in patients with diabetic macular edema
Roche	MPDL3280A, a PD-L1 inhibitor	Metastatic bladder cancer
Roche/Chugai	Alectinib, second-generation ALK inhibitor	ALK+ metastatic NSCLC that has progressed on crizotinib
Sanofi/Regeneron	Dupilumab, an IL-4 and IL-13 blocker	Treatment of adults with moderate-to-severe atopic dermatitis that are not adequately controlled with topical prescription therapy and/or for whom these treatments are not appropriate
ScioDerm	Zorblisa (SD-101)	Inherited epidermolysis bullosa
Spark Therapeutics	SPK-RPE65, a gene therapy that targets inherited retinal dystrophies caused by autosomal recessive mutations in the RPE65 gene	Treatment of nyctalopia, or night blindness, in patients with Leber’s congenital amaurosis due to mutations in the RPE65 gene
Synageva	Sebelipase alfa, a recombinant form of the human lysosomal acid lipase enzyme	Early onset lysosomal acid lipase deficiency, also known as Wolman disease
Syndax	Entinostat, a histone deacetylase inhibitor	Treatment of locally recurrent or metastatic ER+ breast cancer when added to exemestane in postmenopausal women whose disease has progressed following non-steroidal aromatase inhibitor therapy
Takeda	Ixazomib (MLN9708), an oral proteasome inhibitor	Relapsed or refractory systemic light-chain (AL) amyloidosis
Vertex	Combination use of Kalydeco (ivacaftor), a cystic fibrosis transmembrane conductance regulator potentiator, and lumacaftor (VX-809), a CFTR corrector	Cystic fibrosis
Vertex	VX-661, a CFTR corrector, in combination with Kalydeco (ivacaftor)	Cystic fibrosis patients who have two copies of the F508del mutation