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The breakthrough potential of aptamer therapeutics

Since their initial explosion onto the market, there is a growing pipeline demonstrating the promise of aptamer therapeutics across a range of indications.

Aptamer therapeutics progress through clinical pipelineThe first aptamer therapeutic was approved by the FDA in 2004. From the discovery of aptamers in 1990, this was a rapid journey to the first therapeutic approval in just 14 years. Considering the average time for drug development, including all clinical trial phases, is 10-15 years, aptamers showed no delay in proving their therapeutic potential. With the second aptamer therapeutic approved in 2023 and a burgeoning clinical pipeline, aptamers are starting to break through as an effective new therapeutic modality.

The dawn of aptamer therapeutics

When it was approved in 2004, Eyetech’s pegaptanib sodium injection (Macugen) was hailed as a revolutionary, breakthrough treatment for wet AMD, which robbed patients of their sight and had no other FDA-approved treatment. It was the first in what was then a new class of anti-vascular endothelial growth factor (VEGF) drugs and was said to represent a new era in treatment of wet AMD. It also was the first therapeutic drug delivered by intraocular injection. With peak net product revenue of $175-190 million in 2005, pegaptanib led the market for a number of years as an ophthalmologic treatment.

Aptamer therapeutics mature through the pipeline

Since pegaptanib, the emergence of further aptamer therapeutics has been slower, while researchers refined the technology and developed an increased understanding of how best to apply these molecules as therapeutics. But we are now beginning to see this modality making its way through the clinical pipeline to market.

A second aptamer therapeutic, avacincaptad pegol (Izervay), was approved for in September 2023 for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration. Along with being the second RNA aptamer to gain FDA approval, avacincaptad pegol is also the second complement-targeted drug for this cause of blindness. The 39-mer aptamer is conjugated to a polyethylene glycol group and inhibits complement protein C5, which is a central messenger in the innate and adaptive immune responses and a driver of GA.

Similar to pegaptinib, this new aptamer therapeutic is targeted to the eye, though many more of the aptamers in the current pipeline are targeted to alternative tissues and indications from blood disorders to oncology and infectious disease. 

Aptamer TherapeuticDisease indicationPhase 1Phase 2Phase 3Approved
Neovascular wet (age-related) vascular degenerationapproved pipeline arrow
(avacincaptad pegol)
Geographic atrophy secondary to age-related macular degenerationapproved pipeline arrow
BC007Heart failure DCMphase 2 pipeline arrow
BC007Long COVIDphase 2 pipeline arrow
BT200Von-Willebrand disease Type 2Bphase 2 pipeline arrow
BT200Haemophillia A, non-severephase 2 pipeline arrow
AON-D21Severe community-acquired pneumoniaphase 2 pipeline arrow
RBM007Wet age related macular degenerationphase 2 pipeline arrow
(avacincaptad pegol)
Autosomal recessive Stargardt diseasephase 1.5 pipeline arrow
AptollAcute ischaemic strokephase 1.5 pipeline arrow
BT200Haemophilia A, severephase 1.5 pipeline arrow
BT200Von Willebrand disease Type 3phase 1.5 pipeline arrow
BT200Von Willebrand disease Type 1phase 1.5 pipeline arrow
NOXA12Glioblastoma / Brain cancerphase 1.5 pipeline arrow
RBM007Achondroplasiaphase 1.5 pipeline arrow
BB-031Acute ischaemic strokephase 1 pipeline arrow
Apta-1Sepsisphase 1 pipeline arrow
NOXA12Pancreatic cancerphase 1 pipeline arrow
AptollLong COVIDphase 1 pipeline arrow
NOX-E36Solid tumoursphase 1 pipeline arrow
AM003Solid tumoursphase 1 pipeline arrow

Aptamer therapeutics tailored to therapeutic strategy

The flexibility of the aptamer format with both DNA aptamers and modified RNA aptamers available allows different therapeutic strategies to be embraced with aptamer therapeutics. Modified RNA aptamers incorporate inverted thymidine nucleotides to cap the 3’ end, fluorine and O-methyl modified nucleotides within the aptamer sequence, and the addition of a large polyethylene glycol (PEG) group to the aptamer. These modifications are used to extend the half-life of the aptamer therapeutic in vivo.

DNA aptamers, in contrast, typically offer shorter half-lives suitable for ‘hit-and-run’ strategies, where the aptamer therapeutic can quickly reach its target, induce an effect, and be excreted or degraded. In this case, the small size of the aptamer and accessibility of the DNA structure to endogenous enzymes facilitate the short half-life.

Both of the approved aptamer therapeutics are composed of modified RNA. Of the aptamer therapeutics currently undergoing clinical trials seven are composed of RNA, three of DNA and one (AON-D21) is a mixed aptamer, containing nucleotides of both DNA and RNA.

A further integration to support aptamer stability in vivo is the use of enantiomers, which are harder for endogenous enzymes to degrade. Three of the current aptamer therapeutics have utilised this approach, NOXA12, NOXE36 and AON-D21, using L-RNA nucleotides to synthesise the aptamer therapeutic for a longer half life.


As more aptamer therapeutics progress through the clinical pipeline there is increasing evidence of the potential of this therapeutic format, with more lessons learned as we go. At the same time manufacturers are now focused on improving CMC processes for these molecules to support the developers of this new modality, with reduced costs while maintaining the excellent product consistency that has long been associated with aptamers. To find out more about the cost and time to clinic of aptamers download our white paper or get in touch with our experts.

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