dm+d

Unassigned

New Medicines

LyfnuaChronic refractory and unexplained cough

Information

Lyfnua
New molecular entity
Merck Sharp & Dohme (MSD)
Merck & Co (name used in US for MSD)

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Phase III Clinical Trials
Mar 21Filed in US with a PDUFA of 21/12/21 [9].
Feb 21Filed in EU with CHMP decision expected Dec 21 [8].
May 18PIII development has started [5].
Nov 16multinational 12-week PIIb study, n=253 (NCT02612610) completed [1].
Jul 16Afferent Pharmaceuticals acquired by Merck Pharmaceuticals [1].
Apr 16Afferent completed a phase IIb trial which, investigated the efficacy of gefapixant in patients with chronic cough (AF219-010; NCT02349425). They subsequently announced that they would initiate a PIII trial in early 2017 [1].

Category

Purinergic P2X3 receptor antagonist; P2X3 receptors are expressed in afferent neurones that transmit pain perception.
Chronic cough, most commonly defined as cough lasting 3 months or more, is common; a reasonably robust estimate suggests that global prevalence is about 9.6% and European prevalence about 12.7% [2]. There are no effective drug treatments with an acceptable therapeutic ratio [3].
Chronic refractory and unexplained cough
Oral

Further information

Yes
To be confirmed

Trial or other data

Mar 20Merck announce PIII COUGH-1 and COUGH-2 trials meet primary endpoints [7].
May 19Two PIII studies are recruiting [6].
Mar 18PIII study to evaluate the efficacy of gefapixant (MK-7264) in reducing cough frequency as measured over a 24-hour period starts (MK-7264-027; NCT03449134). 720 patients will be recruited in countries around the world, including the US, EU & UK. Collection of primary outcome data (assessment of 24-hour coughs per hour at week 12 & AEs) is expected to complete Jul 20 [6].
Mar 18PIII study to evaluate the efficacy of gefapixant (MK-7264) in reducing cough frequency as measured over a 24-hour period starts (MK-7264-030; NCT03449147). 1,290 patients will be recruited in countries around the world, including the US, EU & UK. Collection of primary outcome data (assessment of 24-hour coughs per hour at week 24 & AEs) is expected to complete Jan 21 [6].
May 17Results of a multi-national PIIb placebo-controlled trial (NCT02612610) published in abstract. Participants (n=253) had refractory chronic cough and were randomised to one of three doses of gefapixant or placebo; primary outcome was change in objectively-monitored cough frequency at 12 weeks compared to baseline. At the highest study dose (50 mg BD), cough frequency was reduced by 37% from baseline; at lower doses (7.5 mg BD and 20 mg BD), frequency was reduced by 22%. Taste disturbance was the most commonly reported adverse effect, causing withdrawal of 10% of patients in the highest dose group [4].

Evidence based evaluations