Inhaled therapy candidate TD139 shows promise in treating idiopathic pulmonary fibrosis (IPF) patients, Galecto Biotech reports.
The results came from a Phase 1b/2a clinical trial (NCT02257177) evaluating TD139 in two parts. Phase 1b was a randomized, double-blind, placebo-controlled, single-ascending dose trial that evaluated the safety, tolerability, pharmacokinetics (how a drug behaves) and pharmacodynamics (how the body reacts to a drug) of TD139 in 36 healthy men.
Phase 2a was a randomized, double-blind, placebo-controlled, multiple dose expansion trial that evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of TD139 in 24 IPF patients.
The findings revealed promising signs that TD139 may help to slow disease progression. After two weeks, those treated with the drug had reduced blood levels of key molecules known to be linked to a worsening of the disease.
TD139 was also found to be well tolerated by all patients without causing serious side effects.
“This is a welcome and much needed breakthrough for the treatment of IPF. This inhaled drug is delivered directly into the lung, is concentrated within lung cells and has minimal side effects in the short term,” Nikhil Hirani, a researcher with the MRC Centre for Inflammation Research at the University of Edinburgh, said in a news release.
The trial was led by the University of Edinburgh in collaboration with scientists from Lund University in Sweden.
Researchers will now evaluate TD139 in a larger IPF clinical study to determine the optimal dose providing clinical benefits.
TD139 is an inhibitor of galectin-3, a protein known to play a key role in fibrosis development in several organs, including the lungs.
“Galectin-3 is also involved in the scarring process in other organs of the body. This research opens up new potential to develop other galectin-3 blockers to treat fibrotic conditions of the heart, liver and kidneys.” said Alison Mackinnon, from the MRC Centre for Inflammation Research.
Galecto presented detailed results of the trial at the American Thoracic Society (ATS 2017) meeting May 21 in Washington, D.C.
IPF is a disease of unknown cause in which tissue deep in the lungs becomes thick and stiff, or scarred, over time. The formation of scar tissue is called fibrosis. As the lung tissue thickens, lungs can’t properly transfer oxygen into the bloodstream; as a result, the brain and other organs don’t get the oxygen they need.
ProMetic Life Sciences Inc.
PBI-4050 IPF data presented at ATS; placebo- controlled trial expected in H2/17
Impact: Neutral
First impression
IPF data shows slight improvement (+2mL) in FVC in combination arm (4050/nintedanib). ProMetic presented new data from its Ph. II IPF trial at the American Thoracic Society (ATS) conference. While we had previously seen interim (Nov/16) and preliminary final data (Feb/17) from the trial, this is the first time PLI has released actual changes in Forced Vital Capacity (FVC). The 12-week study examined patients on PBI-4050 monotherapy as well as two combination therapies (PBI-4050 with BI’s Ofev/nintedanib and PBI-4050 with Roche’s Esbriet/pirfenidone). The PBI-4050 monotherapy arm (n=9) showed a decline in FVC of 12mL after 12 weeks of treatment, the PBI-4050/nintedanib combination therapy arm (n=16) showed a 2mL improvement in FVC, and the PBI-4050/ pirfenidone arm (n=15) showed a 102mL decline in FVC due to drug- drug interactions. The drug-drug interactions resulted in a reduction in PBI-4050 absorption of over 50% as well as an increased rate of metabolism of pirfenidone, leading to a sub-therapeutic level of the drug. We believe that PLI may have to collect additional data to screen for other drug-drug interactions, but anticipate this could be done in a laboratory setting. For reference, the Ph. III trials of nintedanib and pirfenidone, ASCEND and INPULSIS (two INPULSIS studies were performed), showed a decline in FVC (-25 to -30mL) after 13 weeks of treatment vs. a -75 to -100mL decline in patients on placebo.
Comparison to second combination arm (4050/pirfenidone). We note that although there was no placebo arm, the PBI-4050/pirfenidone arm was compared to the other arms by ProMetic in order to analyze statistical significance. The PBI-4050/nintedanib arm, which saw a 2mL improvement in FVC, had a p-value of 0.0376 vs. PBI-4050/pirfenidone, and the PBI-4050 monotherapy arm had a p-value of 0.1359 vs. PBI-4050/ pirfenidone.
Continue to expect placebo-controlled Ph. III trial in Q3/17. Management has revised its guidance for a H2/17 trial initiation, in-line with our Q3/17 forecast. When it provided preliminary final data in Feb/17, management had guided to a Q2/17 initiation. This will be PBI-4050’s first placebo- controlled trial and we believe completion of the trial will be a significant milestone for the company’s small molecule pipeline. The pivotal, placebo controlled trial will examine PBI-4050/nintedanib combination therapy at two doses and PLI will run a second trial studying PBI-4050 monotherapy for patients who failed to tolerate either nintedanib or pirfenidone
WOULD BE INTERESTED IF EVER COMES TO MY AREA FOR CLINICAL TRIAL IVE HAD PULMONARY FIBROSIS FOR 5 PLUS YEARS GRADUALLY GETTING WORSE IAM MALE 69 YEARS OF AGE HOPE TO HEAR SOMETHING SOON THNAK YOU ROBERT KURTEN