Cover Story: It is an RNA world

Table 3. Orphan drug designations. Companies with RNA therapeutics programs receiving orphan drug designations from the FDA.

Source:; BCIQ: BioCentury Online Intelligence

Orphan indication





Spinal muscular atrophy (SMA)

Isis Pharmaceuticals Inc. (NASDAQ:ISIS)

ISIS-SMNRx,A an antisense oligonucleotide that modulates splicing of survival of motor neuron 2 centromeric (SMN2) mRNA

Phase II

Amyotrophic lateral sclerosis (ALS)

LifeSplice Pharma LLC

LSP-GR1, a splice modulating oligomer that reduces the expression of an AMPA 1 glutamate receptor (GRIA1; GLUR1) splice variant



Renal cell carcinoma

Rexahn Pharmaceuticals Inc.

Archexin, an antisense inhibitor of protein kinase B (PKB; PKBA; AKT; AKT1) mRNA

Phase IIa

Pancreatic cancer

Ovarian cancer

Gradalis Inc.

FANG vaccine with shRNA targeting transforming growth factor-b1 (TGFB1) and TGFB2

Phase II

Pancreatic cancer

Isarna Therapeutics GmbH

Trabedersen,A an antisense inhibitor of TGFB2 mRNA

Malignant melanoma

B cell lymphoma

Senesco Technologies Inc. (OTCQB:SNTI)

SNS01-T, an siRNA against eukaryotic translation initiation factor 5A (eIF5A)

Phase I/II

Mantle cell lymphoma (MCL)

Chronic myelogenous leukemia (CML)

Bio-Path Holdings Inc. (NASDAQ:BPTH)

Liposomal Grb-2, an antisense inhibitor of growth factor receptor-bound protein 2 (GRB2)

Phase I

Ewing's sarcoma

The Cure Our Children Foundation

Oligonucleotide against Ewing sarcoma breakpoint region 1 (EWSR1; EWS)


Malignant glioma



Acute myelogenous leukemia (AML)

Lorus Therapeutics Inc. (TSX:LOR; Pink:LRUSF)

Antisense inhibitor of ribonucleotide reductase M2 (RRM2; R2)

Renal cell carcinoma

Gti-2040, an antisense inhibitor of RRM2

Infectious disease

Ebola virus

Sarepta Therapeutics Inc. (NASDAQ:SRPT)

AVI-7537, an antisense oligonucleotide

Phase I

Marburg virus

AVI-7288, an antisense oligonucleotide

Ophthalmic disease

Corneal neovascularization

Gene Signal International S.A.

Aganirsen,B an antisense oligonucleotide targeting insulin receptor substrate 1 (IRS1) mRNA

Phase III

Corneal epithelial defects

CoDa Therapeutics Inc.

Nexagon, an antisense inhibitor of gap junction protein a1 43 kDa (GJA1; CX43; connexin-43)

Phase II

Optic neuropathy

Kunshan RiboQuark Pharmaceutical Technology Co. Ltd.; Biocon Ltd. (NSE:BIOCON; BSE:BIOCON); BioSpring GmbH

QPI-1007, an siRNA inhibitor of caspase-2 (CASP2)

Phase I

Retinitis pigmentosa

Genable Technologies Ltd.

GT038,A an adeno-associated viral (AAV) vector encoding RNAi targeting rhodopsin (RHO; OPN2)


Musculoskeletal disease

Muscular dystrophy

Prosensa Holding N.V. (NASDAQ:RNA)

Drisapersen,A an antisense oligonucleotide targeting exon 51 of dystrophin (DMD)

Phase III

(failed to meet primary end points; new Phase III pending)


Eteplirsen,A a phosphorodiamidate morpholino oligomer (PMO) targeting exon 51 of DMD

Phase II


PRO044,A an antisense oligonucleotide targeting exon 44 of DMD

Phase I/II

PRO045,A an antisense oligonucleotide targeting exon 45 of DMD

PRO055,A an antisense oligonucleotide targeting exon 55 of DMD


PRO052,A an antisense oligonucleotide targeting exon 52 of DMD


SRP-4050, a peptide-conjugated PMO promoting skipping of exon 50 of DMD


PRO053, an antisense oligonucleotide targeting exon 53 of DMD


uniQure N.V. (NASDAQ:QURE)

AAV vector containing modified U11 small nuclear RNA

GlaxoSmithKline plc (LSE:GSK; NYSE:GSK)

An antisense oligonucleotide targeting exon 46 of DMD

Pulmonary disease

Cystic fibrosis

ProQR Therapeutics B.V.

QR-10, an antisense oligonucleotide


Endocrine/metabolic disease


Isis; Genzyme Corp. unit of Sanofi (Euronext:SAN; NYSE:SNY)

Kynamro mipomersen




ISIS-TTRRx, an antisense inhibitor of transthyretin (TTR)

Phase III

Alnylam Pharmaceuticals Inc. (NASDAQ:ALNY)

Patisiran, an siRNA targeting TTR

ALN-TTRsc,B an siRNA targeting TTR

Phase II


Hemophilia A and B


ALN-AT3, an siRNA targeting anti-thrombin III (AT3; SERPINC1) mRNA

Phase I

Polycythemia vera

miRagen Therapeutics Inc.

miR-451, an inhibitor of microRNA-451



Pachyonychia congenita

TransDerm Inc.

TD101, an siRNA targeting N171K mutant form of the keratin 6A (KRT6A; CK6A) gene

Phase I


Renal transplant

SBI Biotech Co. Ltd.; Novartis AG (NYSE: NVS; SIX:NOVN);

Silence Therapeutics plc (LSE:SLN)

QPI-1002,A an siRNA targeting p53

Phase II

Autoimmune disease


Atlantic Healthcare Ltd.; Isis; Orphan Australia Pty. Ltd.

Alicaforsen,A an siRNA targeting

intercellular adhesion molecule-1 (ICAM-1; CD54)

Phase III

ADrug also has orphan drug status from the European Medicines Agency; BDrug has orphan status in EU but not in the U.S.