FDA Grants ALG-801 Orphan Drug Designation for Treatment of Pulmonary Arterial Hypertension

The FDA announced the granting of an orphan drug designation (ODD) to ALG-801 (AliveGen) for the treatment of pulmonary arterial hypertension (PAH), a rare and life-threatening condition characterized by high blood pressure in the long arteries that could lead to right-sided heart failure, according to a news release from AliveGen.¹

Pulmonary arterial hypertension is characterized by hypertension in lung arteries. | Image Credit: © Ahmad | stock.adobe.com

ALG-801, a novel, next-generation ActRII/IIB hybrid ligand trap, is designed to selectively sequester a specific set of Smad2/3 pathway-activating ligands, a mechanism that is essential for the pathogenesis of PAH and a multitude of other diseases. New treatments for PAH have continued to be developed in recent months; ALG-801 joins ZMA001 (Zymedi) as an additional PAH medication granted FDA in the last 6 months.^1,2

“FDA’s orphan drug designation for ALG-801 underscores the need for identifying better treatment options for patients suffering from PAH,” HQ Han, chief executive officer of AliveGen, said in the news release. “We believe that ALG-801, which has demonstrated superior efficacy and improved safety profile in preclinical and clinical phase 1 studies, holds a remarkable potential to become a best-in-class medicine for PAH.”¹

Successfully completed phase 1a and 1b clinical trials in healthy volunteers have demonstrated the efficacy of ALG-801 in patients with PAH. AliveGen announced positive results from the phase 1b multiple-ascending dose study in March 2024, which found that ALG-801 had significant positive effects on muscle gain, fat loss, and insulin sensitization.³

The trial, conducted in postmenopausal women, found ALG-801 was safe and well-tolerated across all dosing cohorts. ALG-801 demonstrated linear pharmacokinetic (PK) exposures, in addition to dose-dependent and statistically significant pharmacodynamic (PD) responses. The results highlight the potential of ALG-801 to serve as a therapy for a variety of conditions, including obesity, neuromuscular diseases, chronic kidney disease, and cardiometabolic disorders.³

PAH includes patients who have heritable disease, drug-induced disease, and idiopathic disease, according to Zachary R Smith, PharmD, FCCP, BCPS, BCCCP at Asembia’s AXS24 Summit in Las Vegas. Up to 50 patients per million could be affected by PAH, according to Smith, with vasoreactivity testing required for patients who meet the necessary criteria for PAH.⁴

Management of PAH uses a prognosis-based algorithm, categorizing patients into low risk, intermediate risk, and high-risk groups, based on the predicted mortality rate at 1 year. Pharmacists play an important role in monitoring variables that may indicate a PAH diagnosis, including noting if a patient is exhibiting cardiovascular difficulties and whether a risk stratification indicates related PAH symptoms.⁴

Once a patient is diagnosed, choosing the right medication is also a role where pharmacists can utilize their expertise. Smith notes that patients at lower or immediate risk are typically started on oral combination therapies, while those at higher risk are treated with an oral combination therapy and prostacyclin [PCN] therapy. ALG-801 represents a unique mechanism of action for typical treatments for PAH, and if approved, could improve outcomes for those at varying risk of disease.⁴

REFERENCES

1. AliveGen. AliveGen receives FDA orphan drug designation for ALG-801 for pulmonary arterial hypertension. BusinessWire. News Release. Released January 7, 2025. Accessed January 7, 2025. https://www.businesswire.com/news/home/20250107878739/en/AliveGen-Receives-FDA-Orphan-Drug-Designation-for-ALG-801-for-Pulmonary-Arterial-Hypertension

2. Gallagher A. FDA grants orphan drug designation to ZMA001 for pulmonary arterial hypertension. Pharmacy Times. Published August 1, 2024. Accessed January 7, 2025. https://www.pharmacytimes.com/view/fda-grants-orphan-drug-designation-to-zma001-for-pulmonary-arterial-hypertension

3. AliveGen. AliveGen announces successful completion of phase 1b multiple-ascending dose clinical trial for ALG-801. BioSpace. News Release. Released March 18, 2024. Accessed January 7, 2025. https://www.biospace.com/alivegen-announces-successful-completion-of-phase-1b-multiple-ascending-dose-clinical-trial-for-alg-801

4. Hippensteele A. Managing pulmonary arterial hypertension: Diagnosis, classification, and treatment strategies. Pharmacy Times. Published April 29, 2024. Accessed January 7, 2025. https://www.pharmacytimes.com/view/managing-pulmonary-arterial-hypertension-diagnosis-classification-and-treatment-strategies