Oral LYT-100 (deupirfenidone) was found to be safe and well-tolerated at all doses in an ongoing Phase 1 trial evaluating its potential to treat disorders involving inflammation and fibrosis, such as idiopathic pulmonary fibrosis (IPF), and disorders of lymphatic flow.
“Based on these results, we plan to move the program forward in multiple indications characterized by inflammation and fibrosis, including IPF, where pirfenidone is shown to have benefit but where tolerability concerns have limited its use,” Daphne Zohar, co-founder and CEO of PureTech Health, its developer, said in a press release.
LYT-100, a small molecule, is designed to be more tolerable for patients than Esbriet (pirfenidone), an approved IPF therapy. Side effects like nausea and fatigue can be common with Esbriet, and a safety study of its long-term and real-world use reporting that nearly 30% of patients stopped the treatment due to adverse events.
Esbriet “is associated with significant tolerability issues and dose-limiting toxicities leading approximately 50% of patients to discontinue use, dose adjust or switch therapies, which results in suboptimal disease management,” the PureTech release stated, citing the above study.
The Phase 1 trial (NCT04243837) in healthy volunteers consists of three parts. The now-complete first part assessed the safety, tolerability, and pharmacokinetics (how the compound moves through and exits the body) of multiple doses of LYT-100, compared to placebo.
Participants were given doses initially increasing from 100 mg up to 750 mg, taken twice daily with food. As all doses were well-tolerated, an additional 1,000 mg dose was added to the trial, which was also well-tolerated.
Pharmacokinetics tests showed that, after eating, exposure to the therapy is similar to that known for Esbriet, but LYT-100 remained at peak therapeutic concentration longer than Esbriet.
Of note, Esbriet’s therapeutic dose is 801 mg, and the treatment is often taken three times daily after a meal. In a previous single-dose crossover study, the company reported that 801 mg of LYT-100 remained at therapeutic levels in the blood longer than 801 mg of Esbriet.
Adverse events associated with LYT-100 were mild and transient, and no trials participant discontinued treatment, PureTech also reported.
The most common side effects across all doses were headache (23.3% with LYT-100 vs. 20.0% with placebo), abdominal distention (10.0% vs. 0% with placebo), nausea (10.0% vs. 0%), and abdominal discomfort (6.7% vs 10.0%).
“The strong results from this Phase 1 readout reinforce our view that LYT-100 has the potential to offer a tolerability and bioavailability profile that could be highly differentiated at the same exposure levels as pirfenidone,” Zohar said.
The trial’s second part will examine the safety, tolerability, and pharmacokinetics of a single dose in healthy volunteers under fasting conditions (without food) to establish an optimal dose. Its third part will assess the same parameters, plus biomarkers and early efficacy in patients with breast cancer-related secondary lymphedema (swelling; lymphedema is a condition affecting the lymphatic flow).
PureTech intends to more fully explore LYT-100 without regard to food consumption, and to conduct additional pharmacokinetics and dosing studies as part of its clinical development for IPF.
Two separate Phase 2 trials are expected to be initiated this year: one evaluating LYT-100’s potential in treating respiratory and other complications related to COVID, and the other a proof-of-concept study in people with secondary lymphedema related to breast cancer.
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