Aptamer therapies offer a new light for big pharma

Astellas Pharma has agreed to acquire Iveric Bio for $5.9 billion this week. Iveric is a biopharmaceutical company focusing on retinal diseases with an open secret of using aptamers to power its pipeline.

What is an aptamer?

Aptamers are affinity ligands composed of DNA or RNA rather than traditional protein-based affinity ligands, like antibodies. Aptamers interact with their targets based on complementary charge and shape. Some obvious advantages of aptamers, such as chemical synthesis, cost of goods, and in vitro discovery and development without the need for animals, provide clear appeal. Over the decades since their discovery, researchers have optimized their format with modified nucleotides incorporated and extensive pegylation added to these aptamers to prevent nuclease activity, renal filtration and extend their half-life in vivo.

Iveric Bio’s lead aptamer

Zimura (Avacincaptad pegol), Iveric Bio's lead asset, is a pegylated RNA aptamer that is a specific and potent inhibitor of complement C5 protein. Having completed phase III trials for geographic atrophy and currently under FDA review for market approval, this aptamer therapeutic is also progressing through phase II trials to treat Stargardt disease.

By autumn, when Astellas’ deal with Iveric Bio is scheduled to complete, Astellas may have an approved GA drug in Zimura, supporting their desired expansion into the gene therapy and vision spaces. Not only that, but Zimura offers the first competitor to Apellis Pharmaceuticals’ GA therapy, with many, including AstraZeneca, Johnson & Johnson, Novartis, and Roche, in pursuit.

Should Zimura be approved by the FDA, this will be the second aptamer therapeutic, following Macugen (pegaptanib), to come to market. Both Macugen and Zimura are modified RNA aptamers intended for ophthalmic use. It appears that aptamer characteristics are well suited to the treatment of the eye.

Engineering aptamer therapies for the future

As our understanding and engineering of aptamers have developed, so has the use of both modified and unmodified RNA and DNA aptamer therapeutics and the range of indications proving treatable with aptamers. Aptamers to multiple indications, from ophthalmology to oncology and infectious disease, are now showing promising results in the clinic. While Zimura and Macugen were modified RNA aptamers, some newer aptamers are unmodified DNA aptamers.

The flexibility of the aptamer format with both DNA aptamers and modified RNA aptamers available allows different therapeutic strategies. Modified RNA aptamers incorporate modified nucleotides and pegylation to prevent nuclease activity and overcome renal filtration. In contrast, DNA aptamers can use a ‘hit-and-run’ strategy, with the aptamer quickly reaching its target to induce an effect and subsequent rapid removal from the body to prevent side effects. In this case, the small size of the aptamer and accessibility of the DNA structure to endogenous enzymes facilitate the short half-life.

Of the current aptamer therapeutics under clinical trial, five are composed of RNA, two of DNA, and one (AON-D21) is a mixed aptamer containing nucleotides of both DNA and RNA.

As more aptamer therapeutics progress through the clinical pipeline, there is increasing evidence of and interest in aptamer therapies.

For more information: https://aptamergroup.com/the-breakthrough-potential-of-aptamer-therapeutics/