Ionis' inhaled antisense medicine demonstrates potential as a novel treatment for cystic fibrosis

- Data from the first clinical study of IONIS-ENAC-2.5 Rx to be presented at North American Cystic Fibrosis Conference

CARLSBAD, CA, USA I October 13, 2020 I Ionis Pharmaceuticals, Inc. (NASDAQ: IONS), the leader in antisense therapeutics, announced today that data from a clinical trial of IONIS-ENAC-2.5Rx demonstrated a significant decrease in the expression of epithelial sodium channel (ENaC) in healthy volunteers. The study showed a mean 55.6 percent decrease (p<0.05) in ENaC mRNA expression at the 75 mg dose in the multidose segment of the trial. The study represents the first time an antisense medicine delivered directly to the lung via a nebulizer has shown a significant reduction in ENaC messenger RNA levels. In preclinical studies, ENaC mRNA reductions of 40 percent or more resulted in significant improvement in mouse models of CF lung disease.

IONIS-ENAC-2.5Rx is an investigational antisense medicine designed to reduce the expression of ENaC in the lung. ENaC is believed to be hyperactive in cystic fibrosis, which is caused by mutations in the cystic fibrosis transmembrane regulator gene. Data from the Phase 1 study will be presented via e-poster at the 2020 North American Cystic Fibrosis Conference, which will hold virtual sessions and discussions Oct. 21-23.

Cystic fibrosis is a life-threatening disease affecting approximately 30,000 people in the U.S. and about 70,000 worldwide. Although CF is a multisystem disease, the main cause of morbidity and mortality is lung disease, characterized by small airway obstruction due to mucus accumulation, decreased mucus clearing and subsequent inflammation, infections and lung function decline.

"We are very encouraged by these data, which demonstrate attractive tolerability and safety for IONIS-ENAC-2.5Rx with substantial target reduction and the convenience of once weekly administration. The data also confirm our expectations for aerosol delivery of antisense medicines for lung diseases based on a wealth of preclinical data," said Brett P. Monia, Ph.D., Ionis' chief executive officer. "These results point to the exciting potential for aerosol delivery of other Ionis medicines that we plan to advance to the clinic, including treatments for chronic obstructive pulmonary disease, or COPD, and severe asthma."

The company also plans to initiate a clinical study to evaluate IONIS-ENAC-2.5Rx in patients with COPD associated with chronic bronchitis starting later this year. IONIS-ENAC-2.5Rx is one of more than 20 potentially transformative antisense medicines in the growing Ionis-owned pipeline that the company is prioritizing and preparing for commercialization.

The primary endpoint of the study was evaluation of safety and pharmacokinetics of IONIS-ENAC-2.5Rx delivered via a Pari eFlow mesh nebulizer. In the single escalating dose study, 32 subjects in four cohorts received a single dose of 3, 10, 37.5, or 100 mg and were followed for 30 days. In the multiple ascending dose study, 24 subjects in three cohorts received four doses of 10, 37.5, or 75 mg once weekly, with an additional dose administered during the first week. An additional cohort of eight subjects received a 37.5 mg dose given thrice weekly for 10 doses. Subjects were followed for 13 weeks after dosing. Fiberoptic bronchoscopy including bronchial brushings and bronchoalveolar lavage was performed during screening and after completion of dosing in the MAD cohorts. Quantitative RT-PCR was performed from the bronchial cell brushings to evaluate ENaC mRNA levels.

About Ionis Pharmaceuticals

As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and only approved treatment for all patients, children and adults with spinal muscular atrophy as well as the world's first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to potentially treat a broad range of disease, including neurological, cardio-renal, metabolic, infectious, and pulmonary diseases.

To learn more about Ionis visit or follow us on twitter @ionispharma.

SOURCE: Ionis Pharmaceuticals

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