RNA-Based Therapeutics in Clinical Trials
Clinical Trials Featuring Oligo-based Therapeutics
The feasibility of oligo-based therapeutics such as microRNAs and microRNA inhibitors is supported by preclinical models and ongoing clinical trials with oligo-based therapeutics. Macugen (Pegaptinib) developed by Eyetech (now OSI Pharmaceuticals) is an FDA-approved RNA-based drug that treats patients with age-related macular degeneration by binding to VEGF. Sirna, Inc. developed siRNA-027, an siRNA targeting VEGFR-1, which has entered a Phase II clinical trial for the treatment of age-related macular degeneration. Alnylam has initiated a Phase I human clinical trial of an inhaled formulation of ALN-RSVO1, an siRNA-based drug for the treatment of Respiratory Syncytial Virus (RSV) infections. The inhaled formulation of ALN-RSV01 used in this Phase I study is delivered via a nebulizer and advances previous clinical work for ALN-RSV01 administered as an intranasal spray. The company previously completed two Phase I human clinical trials of ALN-RSV01 using an intranasal formulation and demonstrated that ALN-RSV01 was safe and well tolerated in healthy volunteers. Another example of RNA-based drugs is GRN163L, an inhibitor of human telomerase developed by Geron, which is presently in clinical Phase I and Phase II trials as an anti-cancer drug in chronic lymphoblastic leukemia and solid tumors. In addition, several antisense oligonucleotides are in Phase II and III trials for a variety of clinical applications.
Phase 3:
Drug (Manufacturer) |
Type of Compound |
Indication (Molecular target) |
| Genasense (Genta) | Anti-Sense Oligo | Varied Cancer (BCL2) |
Phase 2:
| Drug (Manufacturer) | Type of Compound | Indication (Molecular target) |
| Alicaforsen (Isis) | Anti-Sense Oligo | Ulcerative colitis (ICAM1) |
| ISIS 301012 | Anti-Sense Oligo | High cholesterol (apoB-100) |
| ISIS 113715 | Anti-Sense Oligo | Diabetes (PTP1B) |
| ATL1102 (ATL/Isis) | Anti-Sense Oligo | Multiple sclerosis (VLA4) |
| OGX-011 (OncoGenex/Isis) | Anti-Sense Oligo | Prostate cancer (clusterin) |
| SPC2996 (Santaris) | Anti-Sense Oligo | B-cell lymphoma (BCL2) |
| Resten-NG (AVI) | Anti-Sense Oligo | Restenosis (MYC) |
| Sirna-027 (Sirna) | siRNA | Macular degeneration (VEGF) |
Phase 1:
| Drug (Manufacturer) | Type of Compound | Indication (Molecular target) |
| LY21181308 (Lilly/Isis) | Anti-Sense Oligo | Cancer (survivin) |
| LY2275796 (Lilly/Isis) | Anti-Sense Oligo | Cancer (eIF4E) |
| GRN163L (Geron) | Anti-Sense Oligo | Cancer (telomerase*) |
| AVI-4065 (AVI) | Anti-Sense Oligo | Hepatitis C (HCV virus) |
| AVI-4557 (AVI) | Anti-Sense Oligo | Drug metabolism (cytochrome P) |
| Cand5 (Acuity) | siRNA | Macular degeneration (VEGF) |
| ALN-RSV01 (Alnylam) | siRNA | RSV infection (RSV virus) |
*GRN163L targets the RNA component of telomerase rather than telomerase mRNA.