Inhaled IPF therapy LTI-03 awarded orphan drug status in Europe
Rein Therapeutics' drug candidate aims to preserve lung function in patients
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The European Medicines Agency (EMA) has awarded orphan drug designation to Rein Therapeutics’ lead drug candidate, LTI-03, which is being developed to help preserve lung function in people with idiopathic pulmonary fibrosis (IPF).
The designation follows a positive opinion from the EMA’s Committee for Orphan Medicinal Products, which evaluates applications for orphan status, and its subsequent formal adoption by the European Commission.
The status is intended to support the development of medicines for rare diseases — those affecting not more than 5 in 10,000 people in Europe or whose sales returns would be unlikely to justify the investment needed for development. Regulatory incentives include reduced regulatory fees, protocol assistance from the EMA, and 10 years of market exclusivity in the EU upon approval.
LTI-03 has previously received orphan drug designation from the U.S. Food and Drug Administration (FDA).
“This designation represents an important regulatory milestone for Rein and a meaningful step forward for patients living with IPF,” Brian Windsor, PhD, Rein’s CEO, said in a company press release. “Receiving orphan drug designation in Europe provides external validation of our strategy that can do more than slow disease progression. We believe LTI-03 has the potential to address this unmet need.”
LTI-03 contains part of protein that helps regulate fibrosis
IPF, the most common type of pulmonary fibrosis, is a chronic disorder characterized by progressive inflammation and scarring (fibrosis) of lung tissue, which impairs the lungs’ ability to take in oxygen and deliver it to the body.
While the exact causes of IPF are not fully understood, abnormal activation of fibroblasts — cells involved in wound healing — is thought to play a role in the disease process. This overactivation may be triggered by chronic injury to alveolar epithelial cells, which line the lungs’ tiny air sacs where gas exchange occurs, leading to excessive scar tissue formation.
LTI-03 contains part of caveolin-1 (Cav1), a protein that helps regulate fibrosis by maintaining the balance between pathways that initiate and stop the process of wound healing. Cav1 levels are reduced in the lungs of IPF patients.
Delivered directly into the lungs through a dry powder inhaler, LTI-03 is designed to restore Cav1 activity. By doing so, the therapy aims to limit responses involved in activating fibroblasts, reduce the production of profibrotic proteins, and protect healthy alveolar epithelial cells. Taking these effects together, the therapy is intended to halt disease progression.
Therapy shows promise in preclinical studies, trials
According to Rein, the EMA’s final decision was supported by preclinical data demonstrating improved survival and lung function.
In preclinical studies, LTI-03 treatment of lung tissue samples taken from people with IPF reduced the activity of several molecular signaling pathways known to drive inflammation and fibrosis in IPF. LTI-03 also reduced collagen production, the main component of scar tissue.
Initial results from a Phase 1b trial (NCT05954988) showed that twice-daily treatment with low doses (2.5 mg) of LTI-03 reduced levels of several markers of fibrosis and increased levels of a biomarker of alveolar epithelial cell health. Updated analyses that include data from participants treated with higher doses show dose-dependent trends across multiple fibrosis biomarkers.
The therapy is currently being evaluated in an ongoing Phase 2 study, called RENEW (NCT06968845). The study, which started recruiting in May of last year, recently resumed after the FDA lifted a full clinical hold once the company addressed all of the agency’s concerns.
In RENEW, up to 120 adults ages 40 and older who’ve received an IPF diagnosis in the past five years are being randomly assigned to receive either 2.5 mg or 5 mg of inhaled LTI-03 or a placebo twice daily. The trial’s main goal is to assess the therapy’s safety and tolerability over a treatment period of up to 24 weeks, or about 6 months. Secondary outcomes include changes in measures of lung fibrosis and lung function.
Early findings from RENEW suggest that, in addition to reducing markers of fibrosis, LTI-03 helped preserve a type of alveolar epithelial cell that’s essential for tissue repair and regeneration. The therapy was generally well tolerated.
