Pseudohypoaldosteronism type 1B (PHA 1B) is an autosomal recessive disorder caused by loss-of-function mutations in the epithelial sodium ion channel (ENaC). This life-threatening condition usually presents in the first weeks of life with severe dehydration, salt wasting and failure to thrive, symptoms which persist into adulthood. Patients often suffer from respiratory infections and may die from potassium overload and cardiac arrest. Currently, no satisfactory method of treatment exists.
Primary Graft Dysfunction (PGD) refers to acute allograft dysfunction within the first 72 h following lung transplantation in the absence of identifiable secondary causes. PGD is characterized by poor oxygenation and low pulmonary compliance; it affects approx. 30% of all lung transplant recipients for whom it represents a significant cause of early morbidity and mortality. Currently, no satisfactory method of treatment exists.
This was the first time that a development compound has been granted orphan drug designation for these life-threatening condition by the Food and Drug Administration. APEPTICO’s request for orphan drug designation was based on results from experimental lung cell-based studies making use of heterologous expression of mutant versions of the human ENaC, and on data from APEPTICO’s clinical study in lung transplant patients (PGD).
Prof. Bernhard Fischer, CEO of APEPTICO commented: “I am very pleased that the Food and Drug Administration has approved our applications for orphan drug designation for Solnatide for treatment of Pseudohypoaldosteronism type 1B and for treatment of Primary Graft Dysfunction following Lung Transplantation just few weeks after the positive decision of the European Medicines Agency. Until today there exist no approved therapies for these life-threatening conditions.”
About APEPTICO Forschung und Entwicklung GmbH
APEPTICO is a privately-held biotechnology company based in Austria, developing peptide-based products targeting chronic and life-threatening diseases. The peptide molecules correspond to validated, pharmacodynamic active structures and domains of well-known proteins and biopharmaceuticals. By concentrating on synthetically produced protein structures APEPTICO avoids general risks associated with gene- and cell-technologies. APEPTICO makes use of its technology platforms PEPBASE(TM) and PEPSCREEN(TM) to significantly reduce cost and to shorten time to market.
About the APEPTICO’s therapeutic protein structures
APEPTICO’s proprietary therapeutic molecules, such as Solnatide (laboratory code AP301) are synthetically manufactured structural equivalents to domains of the human proteins. Liquid and dry powder formulations of such protein structures can be administered into the lung by inhalation of aerosol particles with diameter 5 micrometres or less. Most recently, APEPTICO has successfully completed two Phase II clinical trials with orally inhaled peptides for treatment of patients with pulmonary permeability oedema and ARDS (acute respiratory distress syndrome) and for treatment of patients with primary graft dysfunction following lung transplantation. For both acute and life-threatening conditions no specific drug-based treatments exist so far.
About Pseudohypoaldosteronism type 1B (PHA 1B)
Pseudohypoaldosteronism type 1B (PHA 1B) or autosomal recessive pseudohypoaldosteronism type I, is characterized by salt wasting from the kidney, colon, and sweat and salivary glands leading to high concentrations of sodium in sweat, stool, and saliva. The disorder involves multiple organ systems and is especially threatening in the neonatal period. Laboratory evaluation shows hyponatremia, hyperkalemia, and increased plasma renin activity with high serum aldosterone concentrations. Sweat and salivary glands, the distal renal tubule, and colonic mucosa are unresponsive to mineralocorticoids. In addition to severe dehydration, vomiting and failure to thrive occurring in the first weeks of life, the clinical picture may be complicated by cardiac dysrhythmias, collapse, shock or cardiac arrest. An increase in the volume of airway surface liquid leads to frequent respiratory tract manifestations and respiratory tract infections are common in affected children. PHA 1B is severe: no remission has been reported and patients suffer from recurrent life-threatening episodes of salt loss requiring salt supplements and control of hyperkalemia to ensure survival. PHA 1B is transmitted in an autosomal recessive manner and is caused by mutations in the genes coding for the subunits of the amiloride-sensitive sodium channel, ENaC resulting in the expression of mutant, loss-of-function ENaC.
About Primary Graft Dysfunction (PGD)
PGD after lung transplantation represents a multifactorial parenchymal injury and dysfunction to the transplanted lung that develops in the first 72 hours after transplantation in the absence of identifiable secondary causes.
The most common indications for lung transplantation are chronic obstructive pulmonary disease (COPD) including emphysema, idiopathic pulmonary fibrosis and cystic fibrosis. Other indications include alpha1-anti-trypsin deficiency emphysema, idiopathic pulmonary arterial hypertension, and sarcoidosis.
PGD is characterized by poor oxygenation and low pulmonary compliance as the main criterion for the condition, formation of interstitial & alveolar oedema, pulmonary infiltrates on chest radiographs, increased pulmonary vascular resistance, intrapulmonary shunt and acute alveolar injury, as revealed by diffuse alveolar damage (IDAD) on pathology. PGD occurs in approx. 30% of lung transplant recipients and it represents a significant cause of early morbidity and mortality to lung transplant patients.
About Orphan Drugs
An orphan drug is a pharmaceutical agent that specifically treats a rare medical condition, the condition itself being referred to as an orphan disease. Orphan drug legislation aim to encourage pharmaceutical companies to develop drugs for rare diseases. Under the law, companies that develop such a drug for an orphan disorder gain marketing exclusivity for 10 years (EU) and 7 years (USA) after marketing approval.