SpliSense's RNA Therapy for Cystic Fibrosis Enters EU Regulatory Fast Lane

JERUSALEM – March 03, 2026
By Kevin Lee

The European Medicines Agency (EMA) has granted a significant regulatory fast-track designation to a novel RNA-based therapy for cystic fibrosis (CF), signaling a new wave of hope for patients with a specific genetic mutation who have limited treatment options. SpliSense, a clinical-stage biotechnology company, announced today that its inhaled drug, SPL84, has received the coveted early Priority Medicines (e-PRIME) designation.

This decision places SPL84 on an accelerated path for development and review, underscoring its potential to address a critical unmet need for CF patients carrying the 3849+10Kb C>T mutation. The e-PRIME status is reserved for medicines that may offer a major therapeutic advantage over existing treatments or benefit patients with no other options, providing a framework of enhanced support from European regulators.

Filling a Critical Gap in CF Treatment

While the last decade has seen revolutionary advancements in CF care with the advent of CFTR modulator therapies, a segment of the patient population remains underserved. The 3849+10Kb C>T mutation, though relatively rare, presents a unique challenge. As a splice-site mutation, it disrupts the proper processing of the genetic instructions needed to create a functional Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein.

Although some patients with this mutation have a milder form of the disease and may see some benefit from existing modulators, the clinical outcomes are often variable and suboptimal. The EMA's Committee for Medicinal Products for Human Use (CHMP) explicitly recognized this gap, noting that even with available modulators, a need persists for therapies offering "substantially improved efficacy," either alone or in combination. SPL84 is designed to meet this very need.

"This PRIME designation represents a major regulatory milestone for SpliSense and for the SPL84 program," said Gili Hart, PhD, Chief Executive Officer of SpliSense, in the company's announcement. "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."

A New Mechanism: Correcting the Message

Unlike CFTR modulators that work on the faulty protein itself, SPL84 takes a different approach by targeting the root of the problem at the genetic level. SPL84 is an antisense oligonucleotide (ASO), a short strand of synthetic genetic material. Administered via inhalation directly into the lungs, it is designed to bind to the faulty RNA message produced by the mutated gene. This binding corrects the splicing error, allowing the cell's machinery to produce a full-length, functional CFTR protein.

The potential of this approach was demonstrated in a recent Phase 2 study. The trial not only showed a favorable safety profile but also yielded compelling evidence of efficacy. Up to 70% of participants treated with SPL84 experienced a clinically significant improvement in lung function, as measured by percent predicted forced expiratory volume in one second (ppFEV1). The study reported an estimated mean absolute improvement of 10 percentage points in ppFEV1 compared to placebo—a substantial gain in the world of CF therapeutics and the first such evidence for an inhaled ASO in any pulmonary disease.

This level of improvement is on par with some of the most effective treatments on the market for other CF mutations, validating the ASO approach and providing a strong foundation for the EMA's decision.

A Clear Path Forward

The e-PRIME designation is the latest in a series of regulatory validations for SPL84, which previously received Orphan Drug and Fast Track designations from the U.S. Food and Drug Administration (FDA). Together, these statuses create a powerful tailwind for SpliSense as it prepares to launch a global Phase 2b study across the United States and Europe. This next trial will aim to confirm the efficacy and safety of SPL84 in a larger group of patients with the 3849+10Kb C>T mutation, including those already taking CFTR modulators.

The enhanced dialogue and scientific advice offered under the PRIME scheme will be invaluable in designing this pivotal study and navigating the complex path to potential marketing authorization. For patients and families waiting for a breakthrough, this accelerated timeline could shorten the wait for a new, life-changing therapy.

Beyond cystic fibrosis, SpliSense is leveraging its RNA platform to tackle other challenging pulmonary diseases. The company is advancing two other programs toward clinical trials expected to begin this year: SPL5AC for muco-obstructive diseases like COPD and asthma, and SPL5B for the relentlessly progressive Idiopathic Pulmonary Fibrosis (IPF). The clinical validation of SPL84 provides a strong proof-of-concept for the company's underlying technology, suggesting that this targeted RNA approach could usher in a new era of treatments for a wide range of debilitating lung conditions.