SPL84 shows signs of improving lung function in CF patients
Phase 2 trial found no severe side effects from investigational therapy
SPL84, an investigational inhalation therapy designed to treat cystic fibrosis (CF) caused by a specific mutation called 3849+10 kb C-to-T, was well tolerated in a Phase 2 clinical trial.
Trial data also suggest that most CF patients treated with SPL84 experienced improvements in a measure of lung function, according to interim results announced in a press release from SPL84’s developer Splisense.
SPL84 therapy administered into the lungs by inhalation
Mutations in the gene CFTR cause CF. These mutations result in a lack of functional CFTR protein, which leads to the production of thick, sticky mucus that builds up in organs and drives most CF symptoms.
Within a cell’s DNA, the CFTR gene comprises sections called exons, which provide instructions to make CFTR protein, interspersed with sequences called introns that don’t encode protein but help to control gene activity.
When the gene is ready to make protein, the entire genetic code is copied over into a temporary molecule called messenger RNA (mRNA). The mRNA then undergoes a process called splicing, where the introns are removed and the exons are strung together to form a mature protein-coding sequence that can be used to make the CFTR protein.
The 3849+10 kb C-to-T mutation leads to splicing problems, resulting in the production of a shortened and dysfunctional version of the CFTR protein. SPL84 is an antisense oligonucleotide, or ASO, which is essentially a short sequence of genetic code. It’s designed to bind to the mutated mRNA and correct splicing to allow production of functional CFTR protein. The therapy is administered into the lungs by inhalation.
According to Gili Hart, PhD, CEO of Splisense, the Phase 2 data “represent the first time an antisense oligonucleotide administered directly to the lungs by inhalation has demonstrated potential efficacy in treating a pulmonary disease.”
After a Phase 1 trial (NCT06217952) in healthy volunteers showed positive safety data, Splisense launched a Phase 2 trial (NCT06429176) designed to test SPL84 against a placebo in adults with CF caused by the 3849+10 kb C-to-T mutation.
[The Phase 2 data] “represent the first time an antisense oligonucleotide administered directly to the lungs by inhalation has demonstrated potential efficacy in treating a pulmonary disease.
The main goal of the ongoing Phase 2 study is to evaluate safety. According to Splisense, results from the first 12 patients showed no concerning trends or signals. No severe side effects related to the therapy were reported.
The Phase 2 study is also evaluating the effects of SPL84 on percent predicted forced expiratory volume in one second (ppFEV1), which is a standard measure of lung function based on how much air someone can forcibly blow out in a quick breath. According to Splisense, up to 70% of patients given SPL84 showed improvements in ppFEV1 relative to what was seen in patients on the placebo, with a mean difference of 10.
“The favorable safety and efficacy profile emerging from our SPL84 program provides clinical validation of our ASO platform. … We remain focused on our mission of developing new treatment options for people suffering from serious pulmonary conditions,” Hart said.
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