BI 1015550: an investigational phosphodiesterase 4B (PDE4B) inhibitor for lung function decline in idiopathic pulmonary fibrosis (IPF)

ABSTRACT

Introduction

The two available therapies for idiopathic pulmonary fibrosis (IPF), pirfenidone and nintedanib, slow down but do not halt IPF progression. Therefore, several agents with specific molecular targets have been recently investigated to find a cure for IPF. Phosphodiesterase 4 (PDE4) inhibition is known for its anti-inflammatory and antifibrotic properties. BI 1015550, an oral preferential inhibitor of the isoform PDE4B, could express complementary activity to current therapies in IPF and other forms of progressive pulmonary fibrosis.

Areas covered

In this review, we first provide an overview toof the current IPF treatment market, followed by the description of pharmacokinetics and pharmacodynamics of BI 1015550. The main preclinical and early clinical evidence on BI 1015550 is then described, as well as its potential as an IPF treatment.

Expert opinion

Oral treatment with BI 1015550 was shown to stabilize lung function as compared to placebo over 12 weeks, both among patients with and without background antifibrotic use, with an acceptable safety profile in a phase 2 trial, and a phase 3 trial has been initiated. To date, this represents to date the largest effect size for an IPF investigational drug tested in a phase 2 trial with the shortest duration.

KEYWORDS:

• PDE4
• BI 1015550
• idiopathic pulmonary fibrosis
• lung fibrosis

Article highlights

• Nintedanib and pirfenidone are the only approved drugs for the treatment of IPF. However, since these therapies do not stop disease progression in these patients, the medical needs in IPF remain unmet.Theunmet. The aberrant repair process characterized by tissue remodeling and fibrosis in IPF involves several inflammatory cells. Inhibition of PDE4 subtypes has been investigated for different clinical indications as they regulate inflammation and modulate immunocompetent cells.

• BI 1015550, a preferential inhibitor of the PDE4B, an isoenzyme which hydrolyzes and inactivates cyclic adenosine monophosphate (cAMP), has been developed for the treatment of IPF and other forms of progressive pulmonary fibrosis.

• BI 1015550 has been recently evaluated in a phase 2, randomized, double-blind, multi-center, placebo-controlled trial that showed a beneficial treatment effect of 18 mg BI 1015550 bid, with the preservation of FVC over 12 weeks together with an acceptable safety and tolerability profile.

• These encouraging findings support further investigation of BI 1015550 as a treatment for IPF and other forms of progressive pulmonary fibrosis in an upcoming confirmatory phase 3 clinical trial.

Declaration of interest

G Sgalla reports personal fees from Boehringer Ingelheim, outside the submitted work. L Richeldi has received grants and personal fees from Boehringer Ingelheim and InterMune, and and personal fees from Biogen-Idec, ImmuneWorks, MedImmune, Roche, Sanofi-Aventis, Shionogi, and Takeda outside of the submitted work.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed membership of advisory boards for Boehringer Ingelheim, and Roche. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.