Phase 1b trial launched of inhaled nintedanib for pulmonary fibrosis
AP02 was developed to reduce side effect risk, dosage level needed
Avalyn Pharma has initiated a Phase 1b clinical trial to test AP02, a therapeutic candidate for pulmonary fibrosis (PF), in adult healthy volunteers.
The placebo-controlled trial of inhaled nintedanib will assess its safety, tolerability, and pharmacological profile when given at single or multiple ascending doses. Its main goal is to determine the incidence, frequency, and severity of adverse events.
“The initiation of this AP02 study marks an important milestone for Avalyn, bringing us closer to delivering a potential new inhaled therapy to patients with pulmonary fibrosis, who are in urgent need of safe and effective treatments that they can tolerate for long-term management of their disease,” Lyn Baranowski, CEO of Avalyn, said in a company press release.
PF, a type of interstitial lung disease, is marked by lung inflammation and progressive fibrosis, or scarring. Its cause in most cases is unknown, a condition referred to as idiopathic PF, or IPF. As the diseases progresses, there’s a decline in the patient’s lung function, accompanied by impairments in their quality of life.
Ofev, an oral nintedanib formulation sold by Boehringer Ingelheim, is an antifibrotic medication approved for IPF and other lung diseases marked by fibrosis. Nintedanib inhibits tyrosine kinase, an enzyme that plays a key role in the cellular mechanisms involved in lung fibrosis. By inhibiting the enzyme, nintedanib can prevent PF symptoms from getting worse, slowing disease progression.
The medication reaches other parts of the body, however, causing serious side effects that may include liver damage, bleeding problems, heart attack, and gastrointestinal issues. These can lead to the treatment being discontinued.
Why was AP02 developed by Avalyn?
To reduce the side effects, Avalyn developed an inhaled formulation of nintedanib, AP02, which is available as a liquid solution that can be inhaled as an aerosols created by a nebulizer. This formulation enables the medication to be delivered directly to the lungs, lowering the dose needed to achieve a therapeutic effect, along with the risk of side effects.
AP02 was well tolerated in a Phase 1a clinical trial (ACTRN12620001141932) that tested its safety and tolerability. The most common side effects considered related to AP02 were cough and headache, followed by nausea and dizziness. All were mild except for one IPF patient who had a moderate headache that was resolved.
The trial enrolled 38 participants, including 32 healthy volunteers and six IPF patients, ages 18-55. Participants in the first three groups were assigned to single ascending doses of AP02 — 0.5, 1, or 2 mg — or a placebo, using Pari’s eFlow nebulizer.
After determining the maximum tolerated dose, or the highest dose that doesn’t cause unacceptable side effects, the healthy participants received either AP02’s maximum dose or 150 mg of Ofev, while the patients received AP02. The results indicated a lower systemic exposure in those who took AP02 over those who took Ofev.
“We’re excited to build on our completed Phase 1a study of AP02 and assess its pharmacokinetic profile to inform our future clinical studies,” Baranowski said.
The Phase 1b trial also seeks to determine AP02’s pharmacokinetic properties, that is, the way it moves into, through, and out of the body, using blood and bronchoalveolar fluid samples.
“I am hopeful that this Phase 1b study will further establish AP02’s potential as a novel inhaled therapy and offer a meaningful clinical benefit to patients,” said Michael Kreuter, MD, professor of pulmonology and head of the pneumology departments at the University Medical Center and the Marienhaus Clinik Mainz in Germany, and a member of Avalyn’s steering committee for AP02. “There is a dire need for effective therapies with tolerability profiles that support longer treatment durations to improve outcomes for patients suffering from pulmonary fibrosis.”
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