BLU-5937, BELLUS Health's lead product candidate, is a potent, highly-selective, orally bioavailable small molecule antagonist of the P2X3 receptor, a clinically validated target for chronic cough.

In November 2018, BELLUS Health announced the positive top-line results from the clinical Phase 1 study for BLU-5937. The Phase 1 top-line data demonstrated that BLU-5937 has a good safety and tolerability profile, as well as a pharmacokinetic profile supporting twice-a-day (BID) dosing. At the anticipated therapeutic doses of 50 to 100 mg, BLU-5937 did not cause any loss of taste perception; only 1 out of 24 subjects reported transient taste alteration.The benign side effect profile, in combination with the anti-tussive effect demonstrated in several preclinical studies, further reinforces the Company’s position that BLU-5937 has the potential to be a best-in-class therapeutic for refractory chronic cough patients.

Results from the Phase 1 study support the advancement to a Phase 2 study, which is expected to be initiated in mid-2019, with top-line results anticipated in mid-2020. This will be a dose escalation crossover design study to assess the efficacy, safety and tolerability of BLU-5937 in patients with refractory unexplained chronic cough, in addition to helping confirm the optimal dose regimen.


Clinical Phase 1 Study Data

On November 19, 2018, BELLUS Health announced the positive top-line results from the clinical Phase 1 study for BLU-5937.

The Phase 1 data demonstrated that BLU-5937 has an excellent pharmacokinetic profile. Plasma half-life was established at 4 to 9 hours, supporting BID dosing. Based on pre-clinical efficacy studies and comparison with drug levels achieved with a clinically validated comparator, the Company anticipates that drug levels required for optimal inhibition of cough will be achieved at 50 mg or 100 mg BID.

BLU-5937 plasma concentration increased dose-proportionally and was not affected by food, supporting BLU-5937 administration without regard to meals.

The Phase 1 data also showed that BLU-5937 has a good safety and tolerability profile. The overall incidence of adverse events was comparable between placebo (50%) and BLU-5937 (44%).

At the anticipated therapeutic doses of 50 mg or 100 mg, BLU-5937 did not cause any loss of taste perception and only one subject out of 24 (4.2%) reported transient taste alteration. This taste effect was reported only on the first day out of seven days of dosing, by a subject receiving 100 mg BID. No subject reported total loss of taste at any dose levels.

At supra-therapeutic doses (200 mg – 1200 mg), two subjects out of 48 (4.2%) reported transient and sporadic partial loss of taste, and 13 subjects out of 48 (27.1%) reported transient and sporadic taste alteration. No subject out of 16 reported any taste loss or taste alteration at 200 mg. All taste-related events were transitory and sporadic in nature; one was rated moderate and all others were rated mild. The other most frequent adverse events reported in the Phase 1 study (>5%) were: headache (11.1%), numbness (11.1%), nausea (8.3%), dizziness (5.6%), and heartburn (5.6%).

There were no serious adverse events and no subjects withdrew prematurely due to an adverse event during the study. No significant trends of mean changes in vital signs, electrocardiogram (ECG) and clinical laboratory values have been observed in the Phase 1 study for BLU-5937.


Clinical Phase 1 Study

The clinical Phase 1 study was a randomized, double-blind, placebo-controlled study of orally administered BLU-5937 in 90 healthy adult subjects. The primary objectives of the clinical Phase 1 study were to assess the safety, tolerability (including taste perception) and pharmacokinetic profile of BLU-5937 in healthy subjects.

The study was divided in two parts:

Part 1: A single ascending dose (SAD) study was conducted in 60 healthy subjects. Subjects were randomized into 6 cohorts of 10 subjects (8 BLU-5937: 2 placebo). The study evaluated single oral doses of BLU-5937 from 50 to 1200 mg.

Part 2: A multiple ascending dose (MAD) study was conducted in 30 healthy subjects. Subjects were randomized into 3 cohorts of 10 subjects (8 BLU-5937: 2 placebo). The study evaluated multiple oral doses of BLU-5937 of 100, 200 and 400 mg administered twice-a-day (BID) for 7 consecutive days.


Clinical Phase 2 Study Design

Results from the Phase 1 study support the advancement to a Phase 2 study, which is expected to be initiated in mid-2019, with top-line results anticipated in mid-2020. This will be a dose-escalation, crossover design study to assess the efficacy, safety, and tolerability of BLU-5937 at four doses: 25, 50, 100, and 200mg BID. In the Phase 1 study, 2.5% of subjects tested at these doses had a taste alteration event. Approximately fifty patients with refractory unexplained chronic cough are expected to be enrolled at 12 clinical sites in the United Kingdom and United States.


Disease and Market

Chronic cough is classified as a cough lasting more than eight weeks. The condition is associated with significant adverse physical, social and psychosocial effects on health and quality of life. In October 2018, the Company commissioned Bluestar BioAdvisors LLC (formerly known as Torreya Insights LLC) to conduct a market assessment through an evaluation of chronic cough epidemiology and pricing estimates. Based on primary and secondary research, the report concludes that, in the United States alone, more than 26 million adults suffer from chronic cough. Of these patients, more than 2.6 million have unexplained or refractory chronic cough lasting for more than a year.

Refractory chronic cough is a significant unmet medical need with no currently approved treatments.

A P2X3 antagonist in development (Merck & Co’s gefapixant) is currently in Phase 3 clinical studies. The compound has previously shown clinically and statistically significant anti-tussive efficacy in multiple Phase 2 studies. However, gefapixant’s cough frequency reduction is coupled with significant tolerability issues, with 80% of patients at the therapeutic dose experiencing taste alteration and/or taste loss.


Pathophysiology of Chronic Cough


Share this

Sign up for email alerts

Email Address *
 
Enter the code shown above.