A versatile set of capabilities are embedded deep into the human fabric, and yet none can be deemed as valuable as our capability to grow on a consistent basis. We say this because the stated reality has already got the world to hit upon some huge milestones, with technology appearing as a major member of the group. The reason why technology enjoys such an esteemed stature among people is, by and large, predicated upon its skill-set, which ushered us towards a reality that nobody could have ever imagined otherwise. Nevertheless, if we look up close for a second, it will become clear how the whole runner was also very much inspired from the way we applied those skills across a real world environment. The latter component was, in fact, what gave the creation a spectrum-wide presence, and consequentially, kickstarted a tech revolution. Of course, this revolution then went on to scale up the human experience through some outright unique avenues, but even after achieving such a monumental feat, technology will somehow continue to produce the right goods. The same has grown increasingly evident in recent times, and assuming one new healthcare-themed development shakes out just like we envision, it will only make that trend bigger and better moving forward.
The US Food and Drug Administration has formally granted Rare Pediatric Disease designation to Avidity Biosciences’ investigational therapy called AOC 1044, which is designed for the treatment of Duchenne muscular dystrophy (DMD) in people living with mutations amenable to exon 44 skipping (DMD44). Before we get into the solution, we must try and understand the condition it will presumably treat. Basically, Duchenne muscular dystrophy, or DMD, is a rare genetic condition best known for causing progressive muscle damage and weakness due to the loss of dystrophin protein, and it all starts at a very young age. For people not aware of dystrophin protein, it bears the responsibility to maintain the integrity of muscle fibers and acts as a shock absorber through its role as the foundation to a protein contingent that connects the inner and outer elements of muscle cells. Anyway, when the performance of this protein takes a hit, it triggers a tear of muscle cell membranes, leading to decline in muscle function over time. During the stated stage, people suffering from it will likely develop problems in walking and breathing, eventually transitioning to a point where their heart and respiratory muscles stop working altogether. If we get into its prevalence, DMD is a monogenic, X-linked, recessive disease which primarily affects males, impacting one in every 3,500 to 5,000 boys across the globe. Now, it’s not to say that we don’t have any approved treatments for DMD at all, but despite their existence, the affected population here continues to feel a severe unmet need. Talk about how Avidity Biosciences’ latest brainchild will solve such a problem, AOC 1044 plans on leveraging phosphorodiamidate morpholino oligomers (PMOs) to deliver on its promised value proposition. You see, by prescribing PMOs to skeletal muscle and heart tissue, the therapeutic will specifically skip exon 44 of the dystrophin gene to enable dystrophin production in cases where DMD is present with mutations amenable to exon 44 skipping (DMD44). Notably enough, this whole mechanism also has in place a proprietary monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a PMO targeting exon 44.
As comprehensive as it sounds, though, FDA’s approval of AOC 1044 only came after Avidity reported, back in December 2023, positive AOC 1044 data in healthy volunteers from the EXPLORE44 trial. A randomized, placebo-controlled, double-blind, Phase 1/2 clinical trial, the stated study saw AOC 1044 delivering unprecedented concentrations of PMO in skeletal muscle, conceiving 50-times greater concentrations than the amount observed in peptide conjugated PMOs in healthy volunteers. Going by the available details, after a single dose of 10 mg/kg AOC 1044, the therapeutic was able to display 1.5% times the exon 44 skipping compared to placebo.
Apart from the Rare Pediatric Disease designation, the new therapeutic was also handed the Orphan Designation and the Fast Track Designation by the FDA.
“We are pleased that the FDA has granted Rare Pediatric Disease designation to AOC 1044, adding to the Orphan Drug and Fast Track designations already granted. The effects of DMD44 are devastating, with symptoms often starting in childhood. These designations by the FDA underscore the urgent need for innovative treatments and validate the potential of AOC 1044 to address the unmet need of people living with Duchenne muscular dystrophy,” said Steve Hughes, M.D., chief medical officer at Avidity Biosciences.
Although approved by the FDA, AOC 1044 remains under a Phase 1/2 trial, where the idea will be to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamic effects of single and multiple ascending doses of AOC 1044 when administered intravenously. For the whole study, Avidity plans on enrolling more than 40 healthy volunteers, and 24 participants with DMD44, both the groups containing participants aged between 7 and 27 years old.
Founded in 2013, Avidity Biosciences has risen up one the back of its proprietary AOC platform, which promises to redefine RNA by combining tissue selectivity of monoclonal antibodies (mAbs) with the precision of oligonucleotide-based therapies. Through redefining, we are, of course, proposing a possibility to more effectively target underlying genetic drivers of diseases. Making company’s prospects even stronger is a fact that it was the first play to complete successful targeted delivery of RNA into muscle. Complimenting the same is Avidity’s clinical development effort that is presently geared towards three rare muscle diseases: myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD).
“We recently shared healthy volunteer data of AOC 1044 from our Phase 1/2 EXPLORE44 trial demonstrating unprecedented delivery of therapeutic oligonucleotide in skeletal muscle and consistent exon skipping in healthy volunteers, and we look forward to sharing data from that study in people living with DMD44 later this year. We remain steadfast in our commitment to advancing science and improving the lives of people and their families affected by this devastating condition,” said Hughes.
