The IPF patients in the open-label trial (NCT02688647) had previously been treated with Genentech’s Esbriet (pirfenidone) or Boehringer Ingelheim’s Ofev (nintedanib) — or had been offered treatment with them. Researchers randomly assigned the trial participants to 400 mg of KD025 or supportive care.
KD025 inhibits Rho-associated coiled-coil kinase, or ROCK2, a molecular pathway involved in IPF and other chronic diseases. Preclinical-trial studies by Kadmon and others have shown that the ROCK pathway is a crucial player in the development of pulmonary fibrosis.
The primary objectives of the 24-week trial were to see whether KD025 was safe and patients could tolerate it well. Researchers also looked at its effectiveness. The yardstick was changes in a lung function measure known as forced vital capacity. FVC is the amount of air a person can exhale after a deep breath.
KD025 reduced patients’ decline in FVC at week 24 by 73 percent, compared with patients receiving supportive care.
It also reduced the percentage of IPF patients whose disease had progressed at week 24, compared with the supportive care group. Twenty percent of KD025-treated patients experienced a 5 percent or larger decline in FVC, versus 44 percent of the supportive care group.
In addition, patients tolerated KD025 well. In fact, none experienced a serious adverse event.
Underscoring these results were that 90 percent of patients who received KD025 decided to continue the treatment beyond week 24.
Twenty patients completed 24 weeks of KD025 by the cut-off date of Feb. 1, 2018, versus nine In the supportive care group.
Kadmon is still enrolling participants in the trial. It anticipates recruiting 36 altogether. You can find more information here.
“We are pleased with today’s results, which demonstrate the activity and tolerability of KD025 in IPF, including in patients who have received prior therapy with approved agents,” Dr. Harlan W. Waksal, Kadmon’s president and CEO, said in a press release. “These findings support the therapeutic potential of ROCK inhibition in IPF and further validate Kadmon’s ROCK inhibitor platform, which is being applied across programs in fibrotic diseases as well as inflammatory diseases.”
“KD025 represents a novel mechanism of action in IPF by inhibiting ROCK, a central regulator of fibrosis that mediates several pro-fibrotic responses,” said Dr. Kevin F. Gibson, the trial’s lead investigator.
Kadmon plans to present the trial results at the American Thoracic Society International Conference in San Diego in May 2018.