- Merck & Co. on Monday divulged details from two pivotal studies testing an experimental pill it's been developing for chronic cough. The pharma first reported in March that the trials had succeeded, without disclosing specifics.
- Merck said the higher of two tested doses of gefapixant significantly reduced the frequency of coughing in chronically affected patients, and in doing so, succeeded where a rival drug from from Bellus Health failed. However, a Cowen analyst cast doubt on the clinical significance of the gefapixant data, saying it will lead to "marginal uptake."
- An estimated 5% to 10% of adults may have chronic cough. If approved, gefapixant would be the first-ever drug specifically for people whose cough is unexplained or can't be treated with other agents. But Merck would not only need to persuade the Food and Drug Administration, but also convince insurers that gefapixant is superior to current treatments, which include low-dose opioids and an epilepsy drug.
Chronic cough, defined as a cough that persists for eight weeks or longer, can occur for many reasons, from smoking to allergies or the effects of certain medicines. In many cases, it can go away when those underlying issues are treated. But sometimes it doesn't. Merck's drug leads an advancing group of experimental drugs aiming to help.
Merck intends gefapixant to be used in patients whose root cause of chronic cough can't be explained, or whose condition has lasted a year, was caused by other health problems and hasn't gotten better with treatment. Patients whose cough was triggered by medications weren't included, since stopping use of those drugs can provide relief.
The data Merck released came from two trials, called COUGH-1 and COUGH-2. Patients in those trials coughed an average of around 18 to 22 times per hour when they began treatment, and those who got a high, twice-daily dose of 45 milligrams of gefapixant saw that number drop to an average of around seven times per hour after 12 weeks. Coughing was measured through a chest contact sensor and a microphone.
Those numbers amounted to a statistically significant improvement compared with placebo patients. But those on placebo also had their cough frequency drop to 10 an hour in COUGH-1 and 8 in COUGH-2.
Patients who got a lower dose of gefapixant did not see a statistically significant reduction in cough frequency over placebo, according to Merck.
Cowen analyst Steve Scala said the benefit in the high-dose group was "small" and will need to be balanced against tolerability concerns that include a taste-related side effect, which affected 58% of those patients in COUGH-1 and 69% in COUGH-2.
Scala also noted the high placebo response made results tough to interpret. The data could suggest, for instance, either that gefapixant overcame a high placebo response, or that that response was the reason for a majority of the drug's positive effects, Scala wrote in a note.
Merck, however, believes the results are strong. "These are the first Phase 3 pivotal studies that have ever been conducted in chronic cough," said Stuart Green, Merck's vice president and therapeutic area head for late stage clinical development for respiratory and immunology, in an interview.
Green noted the effect of chronic cough on patients' quality of life, which can limit such activities as dining out and attending movies in theaters, as well as lead to stress incontinence and depression.
The company is still completing the data package it needs to assemble for the Food and Drug Administration, and hasn't yet set a deadline on when it will file for approval.
But Merck is nonetheless planning ahead for payer negotiations. Green said Merck plans to discuss the quality of life data as well as clinical data as part of its price talks. One of the challenges Merck will face is the relative novelty of treating chronic cough as a distinct condition.
"This has not been a condition that's been high on their radar screen because no real therapy has been effective," Green said.