FDA Requests Additional Info for Liquidia’s Pulmonary Arterial Hypertension Treatment

On November 25th, Liquidia Technologies, a company focused on designing drug particles to ensure optimal delivery of therapeutics, announced that the FDA had given a complete response letter (CRL) for LIQ861 (Treprostinil) inhalation powder for the treatment of pulmonary arterial hypertension. The FDA requested additional information regarding the chemistry, as well as manufacturing data regarding the biocompatibility between the drug and the delivery device. Importantly, the FDA did not mention the need for additional clinical studies.

Pulmonary arterial hypertension (PAH) is a type of high blood pressure caused by narrowed, blocked, or destroyed vessels in the lungs. As a result, the heart needs to work harder to pump blood, which can eventually lead to heart failure and death. Approximately 30,000 people are living with PAH in the US, with around 500-1,000 new cases diagnosed every year. The exact cause of PAH is unknown, with only 15%-20% of patients having genetic mutations that can explain the disease. Several conditions such as cirrhosis, congenital heart disease, scleroderma are associated with PAH. Additionally, consumption of diet pills, methamphetamines, and dasatinib are associated with an increased risk of developing PAH.

There is no cure for PAH; however, several classes of medication can be prescribed to manage the symptoms. These include vasodilators, such as Epoprostenol and Treprostinil, guanylate cyclase stimulators, like riociguat, endothelin receptor antagonist, and others.

LIQ861 Inhalation Powder

Liquidia Technologies’ goal is to design drug particles for better delivery of treatments. By modifying the composition, size, and shape of the particles, Liquidia aims to optimize the performance of existing therapeutics. For LIQ861, Liquidia used their PRINT technology to engineer uniform particles of Treprostinil to enhance deep lung delivery. The formulation allowed for the delivery via a convenient palm-sized, dry powder inhaler. Currently, Treprostinil, a synthetic analog of the vasodilating agent prostacyclin, is administered subcutaneously by an infusion pump or intravenously by a catheter. Both methods are very invasive, which makes the inhaler delivery such an attractive alternative for delivery.

Based on the results from the open-label Phase 3 clinical trial, INSPIRE, where LIQ861 was well tolerated and had no serious adverse effects, the company submitted a New Drug Application to the FDA. The FDA said that it was unable to approve the application. It requested more information and clarification regarding the chemistry, manufacturing, and controls data for the biocompatibility of the drug and the delivery device. Additionally, the inspection and approval of two manufacturing facilities are necessary before approval can occur. The FDA was unable to inspect these facilities was affected due to COVID-19 travel restrictions.

On a positive note, the FDA did not mention the need for additional clinical trials, nor toxicology or pharmacological studies. Liquidia plans to address the FDA’s concerns as soon as possible, and it estimates this setback will not delay their projected launch of LIQ861 in 2022.

“We remain very confident in LIQ861 and are committed to working closely with the FDA to address these items to support its approval,” said Neal Fowler, Chief Executive Officer at Liquidia. “With more than 70 patients now having received LIQ861 for more than two years in our clinical trials, Liquidia remains committed to PAH patients who we believe are underserved with currently available treatment options.”

By Daniel Ojeda, Ph.D.

Related Article: FDA Rejects BioMarin Pharmaceuticals’ Valoctocogene Roxaparvovec Gene Therapy for Severe Hemophilia A

References

1. https://www.globenewswire.com/news-release/2020/11/25/2133620/0/en/Liquidia-Receives-Complete-Response-Letter-from-FDA-for-LIQ861-treprostinil-Inhalation-Powder-for-the-Treatment-of-Pulmonary-Arterial-Hypertension.html
2. https://www.mayoclinic.org/diseases-conditions/pulmonary-hypertension/symptoms-causes/syc-20350697
3. https://rarediseases.org/rare-diseases/pulmonary-arterial-hypertension/
4. https://liquidia.com/about-liquidia/

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Daniel Ojeda