Donidalorsen, also known by its developmental name dawnzera, is an investigational antisense oligonucleotide drug [1]. It is being developed for the treatment of transthyretin amyloidosis (ATTR) [2].
What is Transthyretin Amyloidosis (ATTR)?
ATTR is a progressive, debilitating, and often fatal disease caused by the misfolding and aggregation of the transthyretin (TTR) protein [3]. These amyloid deposits can accumulate in various organs, including the nerves and heart [4]. There are two main types: hereditary ATTR (hATTR), caused by genetic mutations, and wild-type ATTR (wtATTR), which occurs without a genetic predisposition [5].
How does donidalorsen work?
Donidalorsen is designed to reduce the production of the TTR protein in the liver [1]. It achieves this by targeting the messenger RNA (mRNA) responsible for TTR protein synthesis [6]. By reducing TTR levels, the drug aims to prevent the formation of amyloid deposits or even clear existing ones, thereby slowing or reversing disease progression [2][4].
What clinical trials is donidalorsen in?
Donidalorsen is currently being investigated in clinical trials for ATTR [1]. These trials are evaluating its safety and efficacy in patients with both hATTR and wtATTR [2]. Key studies include the cardiovascular and polyneuropathy arms of the ATTRibute-CM and AP101 trials, respectively [7].
How does donidalorsen compare to other ATTR treatments?
Other approved treatments for ATTR include tafamidis, which stabilizes the TTR protein [8]. Gene silencers, such as patisiran and inotersen, also reduce TTR production, but they are delivered via intravenous infusion or subcutaneous injection, respectively [9]. Donidalorsen, if successful, could offer a different dosing regimen or efficacy profile compared to existing therapies [1].
When is donidalorsen expected to be approved?
As an investigational drug, donidalorsen has not yet received regulatory approval from agencies like the U.S. Food and Drug Administration (FDA) [1]. Approval timelines depend on the successful completion of ongoing clinical trials and subsequent review by regulatory bodies [2].
Who is developing donidalorsen?
Donidalorsen is being developed by Ionis Pharmaceuticals [1].
What are the potential risks or side effects of donidalorsen?
Like all medications, donidalorsen may have side effects. The specific risks and side effects are being evaluated in ongoing clinical trials [2]. Common side effects associated with antisense oligonucleotides can include injection site reactions, flu-like symptoms, and liver enzyme elevations [9].
What is the patent status for donidalorsen?
Information regarding specific patent filings and expiry dates for donidalorsen is not publicly detailed in this context. However, Ionis Pharmaceuticals typically seeks patent protection for its novel drug candidates [1].
Where can I find more information on donidalorsen?
More detailed information on donidalorsen, including clinical trial data and regulatory status, can be found on the Ionis Pharmaceuticals website and through clinical trial registries such as ClinicalTrials.gov [1][2].
What is the mechanism of action for antisense oligonucleotides?
Antisense oligonucleotides (ASOs) are short, synthetic strands of DNA or RNA designed to bind to specific mRNA molecules [6]. This binding can prevent the mRNA from being translated into protein or can lead to its degradation, thereby reducing the production of the targeted protein [6]. In the case of donidalorsen, the target is the mRNA for transthyretin [1][6].
Sources:
[1] https://www.ionispharma.com/pipeline/donidalorsen/
[2] https://www.prnewswire.com/news-releases/ionis-provides-pipeline-update-including-advancement-of-next-generation-transthyretin-amyloidosis-treatment-donidalorsen-301885855.html
[3] https://www.nhlbi.nih.gov/health/transthyretin-amyloidosis
[4] https://www.mayoclinic.org/diseases-conditions/amyloidosis/symptoms-causes/syc-20354504
[5] https://www.ameli.fr/assurance-maladie/sante-pratique/maladies/maladies-rares/amylose-transthyretine-ATTR
[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300161/
[7] https://ir.ionispharma.com/news-releases/news-release-details/ionis-announces-positive-topline-results-ATTRibute-cm-trial-patisiran-patients-transthyretin
[8] https://www.fda.gov/drugs/drug-approvals/vyndaqel-tafamidis-and-vyndamax-tafamidis-meglumine
[9] https://www.nejm.org/doi/full/10.1056/NEJMoa2101509