Inhaled nintedanib formulation AP02 found safe in IPF patients

No serious side effects seen in patients, volunteers in Phase 1 trial

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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AP02, an inhaled formulation of nintedanib being developed by Avalyn Pharma, was well tolerated by both healthy people and individuals with idiopathic pulmonary fibrosis (IPF) who took part in a Phase 1 clinical trial.

The open-label study (ACTRN12620001141932) was designed to test the safety and tolerability of AP02 and determine the maximum tolerated dose of the medication. It also compared the pharmacological profile of AP02 with that of Ofev, an approved formulation of nintedanib that is available as oral capsules — but which has been found to lead to serious side effects in patients.

None of the participants who received AP02 experienced serious side effects, the company noted.

“We were especially excited to see the tolerability results of AP02 in those participants with idiopathic pulmonary fibrosis (IPF), an underserved interstitial lung disease with survival rates between 3 and 5 years from diagnosis,” Lyn Baranowski, Avalyn’s CEO, said in a company press release.

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Study focus: Determining the tolerability of AP02

IPF is a disease of unknown cause in which scar tissue forms in the lungs, making it hard to breathe. Over time, scarring (fibrosis) can worsen and cause patients to experience shortness of breath and extreme tiredness. The disease is progressive, and can lead to respiratory failure in patients.

Ofev is an oral medication sold by Boehringer Ingelheim that targets cellular mechanisms associated with lung fibrosis, thereby preventing the symptoms of the disease from getting worse. It is approved for use in adults with IPF or other diseases marked by worsening lung fibrosis.

Because the medication is taken by mouth, it reaches the lungs but also other parts of the body, which can result in serious side effects and treatment discontinuation. These side effects include liver damage, bleeding problems, heart attack, and gastrointestinal issues such as diarrhea, nausea, and vomiting.

To address those complications, Avalyn developed AP02 to be delivered directly to the lungs, which may reduce the dose needed for a therapeutic effect and result in fewer side effects. The medication is available as a liquid solution that can be inhaled in the form of aerosols created by a nebulizer.

“With a nebulized solution that is formulated to be easier to tolerate than the oral systemic therapies, we are hopeful that patients can stay on treatment longer, potentially improving outcomes,” Baranowski said.

The Phase 1 trial of AP02 took place at a single site in Melbourne, Australia, and included 38 participants, ages 18-55, without a history of liver or bleeding problems. Six had a diagnosis of IPF while 32 were healthy volunteers.

The participants were divided into six groups. Groups 1-3 each had eight healthy individuals, who were assigned to receive a single ascending dose of AP02 — either 0.5 mg, 1 mg, or 2 mg — or a placebo using Pari’s eFlow nebulizer. That nebulizer system was designed for daily inhalation therapy for people with chronic diseases affecting the lower airways.

Group 4 had four healthy individuals who received AP02 at the maximum tolerated dose determined in the first three groups. The maximum tolerated dose is the highest dose of a medication that does not cause unacceptable side effects.

In group 5, four healthy individuals received Ofev at a dose of 150 mg. Finally, the sixth group consisted of the six people with IPF, all of whom received AP02 at the maximum tolerated dose.

With a nebulized solution that is formulated to be easier to tolerate than the oral systemic therapies, we are hopeful that patients can stay on treatment longer, potentially improving outcomes.

All were monitored for safety, tolerability, and pharmacokinetics, or how the medication was processed in the body.

The most common side effects deemed related to AP02 were cough and headache, followed by nausea and dizziness. All side effects were mild except one case of headache reported in an IPF patient, which was moderate but resolved.

The company said it plans to share more details from the study at a medical meeting later this year.