What is the role of Lorundrostat in treating adult patients with moderate to severe Obstructive Sleep Apnea (OSA) who have failed or cannot tolerate other treatments such as Continuous Positive Airway Pressure (CPAP) or oral appliances?

Lorundrostat in Treating Obstructive Sleep Apnea

No Evidence for Lorundrostat in OSA Treatment

Lorundrostat has no established role in treating obstructive sleep apnea, as there is no guideline, drug label, or research evidence supporting its use for this indication.

The provided evidence comprehensively covers OSA treatment modalities including CPAP, mandibular advancement devices, hypoglossal nerve stimulation, positional therapy, surgery, and weight loss interventions 1, 2. However, lorundrostat is not mentioned in any guideline or research evidence as a treatment option for OSA 1, 2, 3, 4, 5.

Standard OSA Treatment Algorithm (Without Lorundrostat)

First-Line Therapy

• CPAP remains the gold standard treatment for moderate to severe OSA, improving symptoms, normalizing accident risk, reducing sympathetic activity, and decreasing cardiovascular morbidities 1, 2.
• CPAP should be optimized with mask refitting, pressure adjustments, heated humidification, and behavioral interventions before considering alternatives 2.

Second-Line Options for CPAP-Intolerant Patients

For Mild to Moderate OSA (AHI <30):

• Custom-made dual-block mandibular advancement devices are the first-line alternative, with the highest level of evidence among non-CPAP options 4, 5.
• MADs stabilize the lower jaw in a forward position, maintaining airway patency during sleep 1.

For Moderate to Severe OSA (AHI 15-65):

• Hypoglossal nerve stimulation is recommended for patients with BMI <32 kg/m² who have documented CPAP failure or intolerance 2, 4.
• Patients must undergo drug-induced sleep endoscopy to confirm absence of complete concentric collapse at the soft palate level 2.

Adjunctive Interventions

• Weight loss should be pursued in all overweight OSA patients, though rarely curative as monotherapy 4.
• Positional therapy can be considered for patients with documented positional OSA 4.
• Bariatric surgery may be considered in selected cases with severe obesity 5, 6.

Critical Clinical Context

Lorundrostat is not a recognized pharmacological treatment for OSA. The current evidence base for OSA management focuses on mechanical therapies (CPAP, oral appliances), surgical interventions (hypoglossal nerve stimulation, maxillomandibular advancement), and behavioral modifications 1, 2, 4, 5. While drug therapy targeting pathophysiological traits is mentioned as "promising" in research literature, no specific medications including lorundrostat have established efficacy or guideline support for OSA treatment 5.

Common Pitfall to Avoid

• Do not delay definitive mechanical therapy (CPAP or alternatives) in symptomatic moderate-to-severe OSA while pursuing unproven pharmacological interventions 2.
• Untreated OSA is associated with significant cardiovascular morbidity, mortality, and decreased quality of life 4, 6, 7.