Key Points

• Existing therapies for PAH and PH-ILD are limited by significant side effects and frequent dosing requirements, and there is no cure for PAH. 
• Liquidia’s L606 is an investigational, sustained-release formulation of treprostinil administered twice daily via a next-generation nebulizer designed to enhance drug exposure and reduce side effects.
• Initial findings from an ongoing Phase III open-label study indicate that L606 is well-tolerated and manageable, with no severe adverse events reported.

Pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD) are severe, progressive conditions that profoundly affect patients’ quality of life and survival. PAH involves the hardening and narrowing of pulmonary arteries, leading to right heart failure and potentially death. In 2023, an estimated 31,000 patients in the United States were diagnosed with PAH, as reported by DelveInsight Forecast Report on PAH. Despite treatments that alleviate symptoms and slow disease progression, there is currently no cure for PAH.

On the other hand, PH-ILD includes a wide range of pulmonary diseases, such as interstitial pulmonary fibrosis and chronic hypersensitivity pneumonitis. The diagnosed prevalence of PH-ILD in the United States is estimated to be over 92,000 patients as of 2023, according to the PH-ILD Epidemiology and Market forecast report by DelveInsight. These patients face a poor 3-year survival rate, exacerbated by underdiagnosis and the recent lack of approved treatments until March 2021, when inhaled treprostinil was first approved for this indication. 

Despite advances in treatment, managing these diseases remains challenging due to the limitations of current therapies, which often have significant side effects and require frequent dosing.

Liquidia Corporation is at the forefront of developing innovative therapies to address these challenges. The company is going to present data on the investigational use of L606 (liposomal treprostinil) inhalation suspension at the American Thoracic Society (ATS) 2024 International Conference. This presentation will provide insights into the safety and tolerability of L606 from an ongoing open-label study (Phase III) in the United States. The company expects that the initial data supports the continued confidence that twice-daily dosing is tolerable and titratable. It also supports further investigation as they prepare to initiate a global, pivotal efficacy trial later this year (2024).

The Phase III, two-part, open-label, multicenter study aims to demonstrate the safety and tolerability of L606 in patients with PAH or PH-ILD over both short-term and long-term periods. The trial is enrolling patients in two distinct groups: the Transition group, which includes participants with PAH or PH-ILD who transitioned from nebulized Tyvaso or Tyvaso DPI to L606, and the Naïve group, which includes participants with PAH who added L606 to no more than two non-prostacyclin oral therapies.

 

L606 is an investigational, sustained-release formulation of treprostinil administered twice daily using a next-generation nebulizer. This formulation utilizes Pharmosa Biopharm’s proprietary liposomal technology to encapsulate treprostinil, allowing for a controlled release into the lungs. This method enhances drug exposure over an extended period, potentially reducing local and systemic side effects compared to existing therapies.

In December 2023, Liquidia successfully concluded a Type C meeting with the FDA, agreeing on the registration requirements for L606 using the 505(b)(2) regulatory pathway. It was determined that only a single Phase III placebo-controlled efficacy trial in PH-ILD patients would be required to support indications for treating both PAH and PH-ILD.

The thematic poster session at the ATS 2024 International Conference will showcase the initial findings from the study. Preliminary data from the first 15 patients show that 100% of participants were in the Transition PAH group. A majority of these patients were female (73%), White (80%), non-Hispanic, with a mean age of 61 years. At baseline, 40% were classified as NYHA Functional Class III and 60% as Class II. In terms of adverse events (AEs), 60% of patients experienced at least one mild to moderate AE. Common AEs included dyspnea, blurred vision, dizziness, and cough. Importantly, no severe AEs were reported, and the overall AE profile was manageable, allowing patients to titrate to higher doses as needed.

 

The findings suggest that L606 is well-tolerated and has a favorable safety profile in patients transitioning from other nebulized treprostinil formulations. These promising results support further investigation of L606 in a global, pivotal efficacy trial planned for later this year. Liquidia Corporation’s commitment to advancing this therapy underscores the potential of L606 to improve the management and outcomes of patients with PAH and PH-ILD. The detailed poster presentation will be available on Liquidia’s website following the conference, offering comprehensive insights into the study and its implications for future treatment approaches in pulmonary hypertension. According to DelveInsight analysis, the market for PAH and PH-ILD is expected to grow during the forecast period from 2024 to 2034.