Experimental CF therapy SPL84 granted priority status in Europe
EMA's e-PRIME designation aims to speed development of new treatments
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The European Medicines Agency (EMA) has awarded the early priority medicines designation, known as e-PRIME, to SPL84, an experimental inhalation therapy designed to treat cystic fibrosis (CF) caused by a specific mutation called 3849+10 kb C-to-T.
The EMA grants e-PRIME to investigational medicines that target an unmet medical need. The designation, which aims to speed the development of potentially important new treatments, gives SPL84’s developer Splisense access to perks such as more frequent support from the agency during the drug development process.
“This PRIME designation represents a major regulatory milestone for SpliSense and for the SPL84 program. It reflects the strength of our mechanistic, non-clinical, and emerging clinical data, and reinforces the potential of SPL84 to deliver meaningful benefit to people with cystic fibrosis who continue to represent a significant unmet medical need,” Gili Hart, PhD, CEO of Splisense, said in a company press release.
SPL84 aims to correct splicing defect
CF is caused by mutations in the CFTR gene, which encodes instructions to make the CFTR protein. CF-causing mutations lead to the protein being dysfunctional or entirely absent. As a result, the body produces unusually thick, sticky mucus that builds up in organs, driving most CF symptoms.
When the CFTR gene is read to make protein, the genetic code is copied from a cell’s DNA into a temporary molecule called messenger RNA (mRNA), which is then used as a template to make the protein. The 3849+10 kb C-to-T mutation causes what’s known as a splicing defect — essentially, instead of the mRNA containing the code to make healthy CFTR protein, the mRNA code gets jumbled, preventing production of functional CFTR protein.
SPL84 contains a short piece of genetic material called an antisense oligonucleotide that’s designed to bind to the mutated mRNA and correct this error, allowing cells to produce functional CFTR protein. This, in turn, is expected to help normalize mucus production to ease CF symptoms.
A Phase 1 trial (NCT06217952) in healthy volunteers demonstrated that SPL84 had a positive safety profile. An early Phase 2 trial (NCT06429176) in adults with CF and a 3849+10 kb C-to-T mutation likewise showed positive safety findings, with no serious side effects reported and most patients showing improvements in lung function measures. These early clinical data were included in the European regulators’ review that led to the decision to grant the e-PRIME designation. Splisense is now planning further clinical studies.
“SpliSense is currently advancing SPL84 to a global Phase 2b study in [the U.S.] and EU, designed to further evaluate efficacy and safety in patients with the 3849+10Kb C>T mutation, including those receiving CFTR modulators,” Hart said. CFTR modulators are a class of CF medication that can boost the activity of the dysfunctional CFTR protein in people carrying certain CF-causing mutations.
