MediciNova’s MN-001 for IPF Fails to Slow Lung Function Decline

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by Marta Figueiredo PhD |

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MediciNova's MN-001/pulmonaryfibrosisnews.com/trial results show MN-001 failure

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Six months of treatment with MN-001 (tipelukast), MediciNova’s investigational oral therapy, failed to significantly improve lung function in adults with idiopathic pulmonary fibrosis (IPF), according to data from a small Phase 2 clinical trial.

The therapy, however, was associated with some positive effects, such as a reduction in worsening IPF events. Among the 10 participants with IPF given MN-001 at trial, there were no acute IPF exacerbations or hospitalizations due to respiratory symptoms, the data showed.

“Although our Phase 2 trial in IPF did not demonstrate a clear clinical effect on most of the outcome measures, there were fewer worsening IPF events in the MN-001 group and the [therapy] did demonstrate an effect on reducing LOXL2, a biomarker for IPF,” Yuichi Iwaki, MD, PhD, MediciNova’s president and CEO, said in a press release regarding the company’s second-quarter financial and business update.

The company’s next steps on the clinical path of MN-001 for IPF were not disclosed.

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MN-001 is an orally available small molecule with anti-inflammatory and anti-fibrotic (anti-scarring) properties, and a distinct mechanism of action from that of conventional anti-fibrotic treatments. Its licensing rights outside of Asia were sold to MediciNova in 2002 by its original developer, Kyorin Pharmaceutical.

The therapy works by blocking or reducing the levels of several molecules thought to promote scarring, or fibrosis, including the leukotriene receptor, 5-lipoxygenase, phosphodiesterases, LOXL2, collagen type 1, and TIMP-1. It also lowers the levels of pro-inflammatory molecules.

In an earlier mouse model of pulmonary fibrosis, MN-001 had been shown to significantly reduce lung fibrosis.

The therapy received both orphan drug and fast track designations for IPF from the U.S. Food and Drug Administration between 2014 and 2015. Such statuses were meant to accelerate MN-001’s clinical development and regulatory review.

The now completed Phase 2 clinical trial (NCT02503657) evaluated the safety and effectiveness of MN-001 in 15 adults with moderate to severe IPF, who were recruited at Penn State University College of Medicine, in Pennsylvania.

The participants were randomly assigned to receive either 750 mg of MN-001 (10 patients) or a matching placebo (five patients), twice daily, for 26 weeks (about six months). Those completing the treatment period were given the option to enroll in the study’s open-label extension phase, in which all received MN-001 for six months.

The trial’s main goal was assessing changes in lung function after six months of treatment, as assessed by forced vital capacity (FVC), a measure of how much air a person can exhale during a forced breath. Secondary goals included safety measures and other disease activity assessments, such as changes in exercise capacity, shortness of breath, quality of life, frequency of worsening of IPF, and time to first IPF worsening.

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According to previous baseline (taken at a study’s start) and safety data presented at the recent virtual 2021 American Thoracic Society (ATS) International Conference, the trial involved nine men and six women, with a mean age of 69.9 (range from 53 to 80 years).

The last patient completed the last visit on Dec. 7, 2020. All participants completed the six-month treatment period, and all but one completed the study’s extension phase.

MN-001 was found to be generally safe and well-tolerated, with the most commonly reported adverse events being gastrointestinal problems. All 15 patients experienced at least one adverse event, and three serious adverse events, deemed unrelated to the therapy, were reported.

Newly announced data showed that the trial failed to meet most of its main and secondary goals, with no clinically meaningful trends favoring MN-001 over the placebo.

However, none of the MN-001-treated patients experienced a worsening IPF event, such as acute symptom exacerbation or hospitalization required by respiratory symptoms, compared with one patient reporting such an event in the placebo group.

Also, while the levels of LOXL2 — a biomarker of IPF — were substantially reduced in the MN-001 group, they were increased in the placebo group. This confirmed that the investigational therapy was effectively suppressing its known targets.

MN-001 also is being tested in clinical trials as a potential therapy for nonalcoholic fatty liver disease or NAFLD, the company said. NAFLD is characterized by fat accumulation in the liver, and nonalcoholic steatohepatitis or NASH, an aggressive condition marked by liver inflammation and fibrosis. Iwaki said MediciNova is working with collaborators on a planned Phase 2 trial of MN-001 in NASH.

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