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)
Not recommended for approval (Negative opinion)
Jan 22The US FDA has rejected gefapixant, issuing a complete response letter (CRL) to Merck in which the agency requests additional information relating to measurement of efficacy. The CRL was not related to the safety of gefapixant. Merck is reviewing the letter and will meet with the agency to discuss next steps. [13,14].
Jul 21The FDA has extended the PDUFA action date to 21/03/22 to provide time for a full review of the submission [10].
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

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