BLU-5937 may SOOTHE refractory cough

Individuals with refractory chronic cough (RCC) may find relief in BLU-5937, a selective P2X3 antagonist under development which showed favourable efficacy in reducing cough frequency in the phase IIb SOOTHE trial.

Despite adequate treatment of all identifiable associated disease or without identifiable cause, RCC may persist for ≥8 weeks. [Eur Respir J 2020;55:1901136; Chest 2018;153:196-209] “[Individuals with RCC] experience a high frequency of cough, interfering with quality of life,” said the researchers.

“[T]here is currently no approved treatment to help relieve cough in these patients … [This] exacerbates the significant physical, psychological, and social burdens RCC imposes on patients,” they continued.

“[In our study, the likelihood of] achieving a clinically meaningful cough frequency reduction favoured treatment at every dose of BLU-5937 over placebo at day 28,” said the researchers.

After a single-blind run-in period, 249 participants from the main cohort who had maintained a baseline awake cough frequency ≥25 coughs/hour were randomized 1:1:1:1 to the three BLU-5937 arms (12.5, 50, and 200 mg BID) or placebo for 4 weeks of double-blind treatment. [ATS 2022, abstract A5608]

The frequency of 24-hour cough markedly dropped with the two higher doses of the active agent as opposed to placebo, both at day 15 (–47 percent [50 mg] and –49 percent [200 mg] vs –22 percent [placebo]) and day 28 (–53 percent [both doses] vs –28 percent).

At day 28, more than half of participants receiving BLU-5937 experienced at least 30-percent improvement in 24-hour cough frequency (52, 61, and 62 percent with the respective 12.5-, 50-, and 200-mg doses). Only a third (36 percent) of placebo recipients were able to achieve this endpoint. This trend was already evident by day 15 (48, 55, and 56 percent vs 32 percent).

At least half of BLU-5937 recipients were able to achieve ≥50-percent improvement in 24-hour cough frequency (35, 44, and 48 percent for the respective 12.5-, 50-, and 200-mg doses), while about a quarter reported ≥70-percent improvement (19, 25, and 19 percent, respectively). The corresponding percentages in the placebo arm were lower at 14 percent (≥50-percent improvement) and 7 percent (≥70-percent improvement).

Day 15 also saw more active agent vs placebo recipients reporting ≥50-percent (24, 32, and 35 percent in the respective 12.5-, 50-, and 200-mg arms vs 15 percent [placebo]) and ≥70-percent improvement (12, 13, and 18 percent, respectively, vs 7 percent).

Across thresholds of response at day 28, the cumulative odds ratios were 2.2 (p=0.0276), 3.4 (p=0.0008), and 3.3 (p=0.011) for the respective 12.5-, 50-, and 200-mg doses.

“The results suggest that participants treated with BLU-5937 were consistently more likely to experience not only a minimal clinically important change in cough frequency (≥30-percent reduction), but are also more likely to experience more important reductions in cough (≥50- and ≥70-percent reduction),” said the researchers.

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