BLU-5937, BELLUS Health's lead drug candidate, is a potent, highly selective, orally bioavailable small molecule antagonist of the P2X3 receptor, a clinically validated target for chronic cough. BLU-5937 has the potential to be a best-in-class therapeutic for chronic cough patients who do not respond to current therapies.

On November 19, 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.

Based on these data, the Company is preparing for the clinical Phase 2 study in chronic cough patients beginning 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 chronic cough patients, in addition to helping confirm the optimal dose regimen.

In preclinical studies, BLU-5937 exhibited a potent anti-tussive effect without affecting taste perception and an excellent safety profile.


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%).

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.

No subject reported total loss of taste at any dose level. Only one subject out of 24 (4.2%) reported taste alteration at the anticipated therapeutic doses of 50-100 mg. This taste effect was reported only on the first day out of 7 days of dosing in a subject receiving 100 mg BID. There were only 2 cases of transient and sporadic partial taste loss reported: one at 400 mg BID and one at the 800 mg single dose level. At supra therapeutic doses of 200 mg to 1200 mg, 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 adverse events were transitory and sporadic in nature and almost all of them were mild. The other most frequent adverse events reported in the Phase 1 study (> 5%) for BLU-5937 were: headache (11%), numbness (11%), nausea (8%), dizziness (6%) and heartburn (6%).


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

Based on the positive top-line data from the Phase 1 study, BELLUS Health expects to initiate a clinical Phase 2 study for BLU-5937 in chronic cough patients 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 chronic cough patients, in addition to helping confirm the optimal dose regimen. A total of 50 patients with refractory unexplained chronic cough are expected to be enrolled in approximately 10 clinical sites located in the United Kingdom and Unites States.


Disease and Market

Chronic cough is associated with significant adverse social, psychosocial and physical effects on quality of life. Chronic cough, defined as a cough that lasts more than eight weeks, is estimated to affect approximately 10% of adults in the U.S. While an underlying etiology may contribute to cough in some of these patients, including gastro-oesophageal reflux, asthma, or allergic rhinitis, an underlying condition cannot be identified in 10%-20% of chronic cough patients (unexplained chronic cough). A portion of patients with an underlying condition as well as the large majority of unexplained chronic cough patients are not well controlled by current therapies.

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 and more than 2.6 million of these patients have chronic cough lasting for more than a year. The number of treatment-refractory chronic cough patients expands to 11.7 million when taking into account those patients with a cough duration between eight weeks and one year. The market assessment also sought to better understand the pricing and reimbursement landscape for a condition that has no recently-approved therapies, and therefore no direct comparables. Based on interviews with Key Opinion Leaders, prescribing physicians and payers, the consensus is that new chronic cough treatments, such as BLU-5937, will be priced similarly to therapies for chronic constipation, asthma and partial onset seizures. These analogs represent non-lethal chronic conditions that have a significant impact on quality of life and address a large patient population in competitive markets that also include generic and over-the-counter products. The monthly price for these analogs varies between US $300 and $600.

BELLUS Health secured patent protection for BLU-5937 in all major pharmaceutical markets. Patents were granted by the European Patent Office and the Japan Patent Office in 2018, in addition to patents granted in the United States and China in 2017, with claims covering the composition of matter of BLU-5937 until 2034. In addition, the Company further expanded BLU-5937’s patent protection to 2038 by securing a new U.S. patent claiming P2X3 selectivity as a means of minimizing taste effects.


Pathophysiology of Chronic Cough


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