At Tuesday's ILD Support Group Meeting, Dr. Paul Wolters discussed the results of three of the Phase 3 trials, which were announced at the recent American Thoracic Society's International convention in San Diego.
All three trials included patients from my university hospital. Patients with IPF participated in one of these trials.
1. N-Acetyl Cysteine (NAC)
Rationale:
Oxidants injure lungs. NAC is an anti-oxidant.
Blind Trial: 264 people in 25 centers were given either a placebo or 600 mgs 3x a day (1:1) of NAC. They had mild to moderate IPF, a FVC of 50% or higher and a DLCO of 30% or higher.
Primary Endpoint: Change in FVC at 60 weeks.
Secondary Endpoint: Survival, rate of acute exacerbations, 6-minute walk distance, quality of life.
Results: NAC group lost 150 ccs of lung function, which was the same rate as those on placebo. NAC did not prevent loss of lung function in IPF. It was well tolerated. It is recommended to stop taking NAC if the patient has IPF.
2. Pirfenidone
Rationale:
Drug blocks development of fibrosis of the lungs
Prior to Phase 3 trial suggested it slowed the loss of lung function
Approval already in Japan, Canada, Indian and some countries in Europe
Blind Trial: 555 people in 127 centers in 9 countries with mild to moderate IPF were given either a placebo or 2403 mgs/day (1:1)
Primary Endpoint: Change in FVC at 52 weeks
Secondary Endpoints: Survival rate, change in 6-mile walk distance, quality of life, progression slowed
Results: The group on placebo lost 400 ccs of lung capacity in 52 weeks with the group on Pirfenidone only lost 200 ccs in 52 weeks. It cut the lost of lung function by half.
There were actually three trials and the data was pooled. Fewer people on Pirfenidone died compared to the other group. It prevented death and preserved lung function.
Side Effects: There were side effects including nausea, rash and anorexia. Since 90% of the patients stayed on the drug for the duration of the trial, this is considered tolerable. The FDA had been concerned about Risk vs Benefit.
The final conclusion: Pirfenidone slowed progress in IPF, improved survival with moderate side effects that are manageable. It works but they have yet to discover exactly how it works.
3. Nintedanib
Rationale: Tyrosine Kinase inhibitor which blocks collagen secretions, fibroblast growths and blood vessel growth. Prior to this study, the Phase 2 trial suggested that it slowed the loss of lung function in patients with IPF.
Trial: 1066 people in 205 centers in 24 countries participated in two blind trials were run simultaneously where 150 mgs 2x a day of Nintedanib was given to a randomization with a placebo group of 3:2. Each had mild to moderate IPF.
Primary Endpoint: Change in FVC at 52 weeks
Secondary Endpoint: Time to first exacerbation (flare), quality of life, death
Results: The placebo group lost 200 ccs of FVC while the group on the drug lost 100cs FVC. Acute exacerbation were not common and only experienced by 6-7%. Survival of those on the drug had better survival rates.
Side Effects: Diarrhea was experienced by 50% of the group taking the drug (and 20% by the placebo groups as it was known to have this problem. People were hoping to have the side effect so they knew they were getting the drug) and 25% experienced nausea. The dose was adjusted, which helped with these side effects and 90% of the patients stayed on the drug for the duration of the study.
Conclusion: Slows IPF by 50% compared to the placebo group. The trend is towards improving survival and has moderate side effects, which is mostly manageable.
My question to the good doctor was if there would by any studies with these drug including patients with a variety of ILDS. The insurance companies will not approve these drugs off label for a while. Maybe years. Those of us with other ILDs will have to pay out of pocket for these drugs, which will be thousands of dollars a month. Hopefully, this dance with the insurance companies will be quicker than the normal process. Our lives depend on it.
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