Negative results from phase II study of LYT 100-COV in post-acute "long" COVID with respiratory complications.

There was no treatment effect observed in this indication with LYT-100, though the strong safety and tolerability profile of LYT 100 seen in previous studies was reaffirmed.

Based on these data, PureTech will not pursue further studies in this patient population and remains on track to initiate registration-enabling studies of LYT 100 in idiopathic pulmonary fibrosis (IPF) later this month. LYT 100 is a selectively deuterated form of pirfenidone. Pirfenidone has been proven effective in IPF, a devastating condition where the tolerability, safety and potentially higher exposure of LYT 100 could have an important impact on patient adherence and outcomes.

The global, double-blind, randomized, placebo-controlled study is one of few to complete in patients with post-acute COVID. The study enrolled 177 patients averaging 55 years of age who experienced continued respiratory complications following hospitalization for acute COVID-19 infection that required treatment with supplemental oxygen. The primary efficacy endpoint was a three-month change from baseline compared to placebo on the six-minute walk test (6MWT) distance. The 6MWT determines how far a patient can walk in six minutes and is a commonly used measure of functional capacity in a variety of cardio-pulmonary diseases. Individuals in both the treatment and placebo arms meaningfully improved walking distance on the 6MWT as compared to baseline, and no statistically significant differences between treatment groups were observed.

LYT-100 was well-tolerated in this relatively sick patient population with multiple comorbidities and concomitant medications.

There were no drug-related serious adverse events (SAEs) or deaths. Nausea was the only AE judged to be at least possibly related to LYT-100 with an incidence greater than 5% (8.7% vs 2.4% with placebo). Other AEs that have been commonly associated with pirfenidone and were considered to be at least possibly related to LYT-100 treatment included headache (4.3% vs. 1.2% with placebo), dizziness (3.3% vs. 1.2% with placebo), fatigue (2.2% vs. 0% with placebo), and rash (3.3% vs. 1.2% with placebo). Discontinuation rates due to AEs that were considered at least possibly related to LYT 100 were low in both arms (8.6% with LYT 100 vs. 2.4% with placebo) and the majority of discontinuations in the LYT 100 arm were due to idiosyncratic events and not AEs commonly associated with pirfenidone. These results are consistent with the previously demonstrated safety and tolerability profile of LYT 100, including the recently announced results of a crossover study in healthy older adults, which showed that approximately 50% fewer subjects experienced gastrointestinal-related AEs with LYT 100 compared with pirfenidone (17.4% vs. 34.0%) and that substantially fewer subjects experienced AEs with LYT 100 vs. pirfenidone. PureTech has also recently shown that LYT 100 can be safely dosed with a higher total drug exposure than the currently approved dose of pirfenidone, which could translate into improved efficacy over pirfenidone.

The safety and tolerability data generated to date with LYT 100, along with the established efficacy of pirfenidone in IPF, support the advancement of registration-enabling studies of LYT 100 in IPF.

World Health Organization has said evidence suggests as many as 10%-20% of people experience a range of mid-and long-term effects after the initial illness, known as post COVID-19 condition or long COVID, which include fatigue and shortness of breathe.

The trial was always considered a long shot – or an ‘exploratory study’ in the words of PureTech CEO Daphne Zohar – as the long-term effects of COVID-19 infection are very broad and the condition is still not well understood.