Report RCC Therapeutics 2026–2035
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December 2025

Refractory Chronic Cough (RCC) Therapeutics

Pipeline Analysis & Competitive Landscape 2026–2035

52 pages
Updated December 2025
Supported by Hyfe Inc.
$9B$15B
Market Size 2026–2035
~100M
Patients Worldwide
17
Therapeutics in Pipeline
Executive Summary

A Market at Inflection Point

Refractory Chronic Cough remains a large, undertreated, and globally unaddressed condition. The first U.S. approval—expected no earlier than 2026—will create a new therapeutic category.

01

Massive Unmet Need

~100M affected worldwide with no FDA-approved therapies. Current practice relies on off-label medicines with 31–40% adverse event rates and modest efficacy.

02

Regulatory Reset

Two Complete Response Letters for Gefapixant raised the bar: FDA now requires ≥30% placebo-adjusted reduction in objective 24-hour cough frequency.

03

Pipeline Clarity

Camlipixant leads with ~34% efficacy and <7% taste AEs. Nalbuphine ER shows highest efficacy (60% reduction). The U.S. market will likely see one winner, at most two.

04

Digital Inflection

Digital therapeutics deliver ~40% cough reduction with no drug toxicity and extend pharmacologic persistence by 30%, improving lifetime value by ~44%.

Central Thesis

"Therapies capable of demonstrating ≥30% placebo-adjusted efficacy, low discontinuation, durable symptom control, and digital integration will dominate the market and define the first generation of approved RCC treatments."

What's Inside

01
Introduction
02
Market Landscape
03
Growth Dynamics
04
Commercial & Access
05
Pipeline & Strategy

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02

Market Landscape

Market Context

The chronic cough market is valued at approximately $9.8B in 2024 across the 7 Major Markets, projected to reach $14.9B by 2035 (CAGR ~6%).

Patient Population

  • Global chronic cough: 450–600M
  • Global RCC: ~100M
  • U.S. RCC: ~10M individuals
  • Commercially reachable: 20–30M globally; 2–4M in U.S.

Growth Drivers

Aging populations, specialist referral expansion, digital identification tools, and increasing recognition of cough hypersensitivity syndrome are driving market growth.

Investment Thesis

Zero approved drugs for RCC in the U.S. creates first-mover advantage opportunity.

GSK's $2B acquisition of Bellus Health validates the market opportunity.

~$14B+ projected market with 31% of patients failing all current treatments.

Key Risks

  • Efficacy ceiling / 30-60% placebo response in P2X3 RCTs
  • FDA approval uncertainty post-Gefapixant precedent
  • Economic evidence gap (QALY / CEA)
  • Digital therapeutics disruption
03

Market Outlook & Growth Dynamics

Market Size Forecast

The RCC treatment market is projected to grow from $10.4B in 2025 to $18.5B by 2035, representing a CAGR of approximately 5.9% globally.

Regional Growth Rates (CAGR 2025-2035)

Region CAGR
United States 6.4%
South Korea 6.2%
European Union 6.0%
United Kingdom 5.8%
Japan 5.7%

Three Boxes for Commercial Success

Success Criteria

Efficacy: >30% cough reduction (placebo-adjusted)

Tolerability: Taste AEs <10%

Durability: 24–52 weeks without tachyphylaxis

Camlipixant Performance

Phase 2b SOOTHE trial demonstrated 34.4% reduction at 50mg BID with only 6.5% taste AEs—meeting all three success criteria.

04

Commercial, Economic & Access Landscape

Mechanism Benchmarking

Mechanism Adj. Efficacy Key AEs
P2X3 (Camlipixant) 34% 6.5% taste
KOR/MOR (Nalbuphine) 43-57% Nausea, sedation
Digital BCST 41% None
P2X3 (Gefapixant) 14-19% 50-81% taste

Payer Considerations

Without stronger HEOR evidence, even efficacious therapies may see restricted access or price compression. Key barriers include high OOP costs, step therapy requirements, and geographic SLP access limitations.

Reimbursement by Market

  • United States: No approved drug; PA/step therapy expected
  • UK: NICE appraisal terminated (Apr 2024)
  • EU: Gefapixant approved; country-by-country HTA
  • Japan: Gefapixant reimbursed at ¥11,250/mo after 7.7% price cut
Healthcare Utilization

Median time to diagnosis: 6.5 years

60% see ≥1 specialist

57% prescribed ≥4 medications

49% see ≥4 physicians before diagnosis

05

Pipeline, Strategy & Scenarios

Pipeline Scorecard

Asset Stage Next Milestone
Camlipixant (GSK) Phase 3 CALM-1/2 H2 2025
Nalbuphine ER (Trevi) Phase 2b Phase 3 H1 2026
Taplucainium (Nocion) Phase 2b Topline 2025-26
Hyfe DTx (Kyorin) Pre-launch Japan 2027

The Placebo Problem

60-85% placebo response rate complicates clinical development. Gefapixant Phase 3 showed only 6.9% absolute difference vs active in responder rates.

Digital Therapeutic Value Proposition

DTx ROI Model

Average duration: 7 months → 9.1 months (+30%)

Revenue/patient: $7,700 → $10,010 (+30%)

LTV (3-year): $15,400 → $22,110 (+44%)

ROI: 7.7:1

Scenario Analysis (NPV)

  • Bear Case: $7.87B cumulative
  • Base Case: $9.44B cumulative (+DTx)
  • Bull Case: $12.0B+ cumulative

Digital integration delivers +$1.57B value lift (+20%) in base case scenario.

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