Perfluorohexyloctane Ophthalmic Solution: A Review in Dry Eye Disease.

Perfluorohexyloctane ophthalmic solution (Miebo®) is a single-entity, water-, steroid- and preservative-free, first-in-class semifluorinated alkane that is approved in the USA for the treatment of the signs and symptoms of dry eye disease (DED). DED is often linked with meibomian gland dysfunction (MGD), which causes an excessive evaporation of tears. Perfluorohexyloctane ophthalmic solution stabilizes the lipid layer of the tear film and inhibits tear evaporation by forming a monolayer at the air-liquid interface. In the phase III GOBI and MOJAVE trials in adults with DED associated with MGD, one drop of perfluorohexyloctane ophthalmic solution instilled in each eye four times daily over 8 weeks resulted in statistically significant and clinically meaningful improvements in the signs and symptoms of DED compared with hypotonic saline (0.6%). The agent was generally well tolerated, with most ocular adverse events being mild or moderate in severity. The efficacy and tolerability of perfluorohexyloctane ophthalmic solution was sustained for up to 52 weeks in an extension study (KALAHARI). As the first and currently the only prescription treatment approved in the USA directly addressing the pathophysiology of excessive tear evaporation, perfluorohexyloctane ophthalmic solution is a valuable emerging option for the management of DED.

Dry eye disease (DED) is a common eye disorder caused by many factors. In most cases, DED is linked with meibomian gland dysfunction (MGD), which causes an excessive evaporation of tears. Perfluorohexyloctane ophthalmic solution (Miebo^®), a single-entity, water-, steroid- and preservative-free, first-in-class semifluorinated alkane, is approved in the USA for the treatment of the signs and symptoms of DED. The agent stabilizes the lipid layer of the tear film and prevents the evaporation of tears by forming a layer on the surface of the tear film. In two phase III clinical trials in adults with MGD-associated DED, one drop of perfluorohexyloctane ophthalmic solution instilled in each eye four times daily over 8 weeks led to significant improvements in the signs and symptoms of DED when compared with hypotonic saline (0.6%). Perfluorohexyloctane ophthalmic solution was generally well tolerated, with most ocular adverse events being mild or moderate in severity. Thus, as the first and currently the only prescription treatment approved in the USA directly addressing excessive tear evaporation, perfluorohexyloctane ophthalmic solution is a valuable emerging option for the management of DED.

Mitapivat: A Review in Pyruvate Kinase Deficiency in Adults.

Mitapivat (Pyrukynd®), an oral, allosteric activator of pyruvate kinase (PK), is approved in the USA for the treatment of haemolytic anaemia in adults with PK deficiency and in the EU and UK for the treatment of PK deficiency in adults. Mitapivat acts by restoring activity of the red blood cell (RBC) PK enzyme, which is dysfunctional due to genetic mutations in the PKLR gene in patients with PK deficiency. In the double-blind placebo-controlled phase III ACTIVATE trial in adults with PK deficiency who were not regularly RBC transfused, mitapivat was superior to placebo in improving haemoglobin levels. In the single-arm phase III ACTIVATE-T trial in adults with PK deficiency who were regularly RBC transfused, a reduction in RBC transfusion burden was observed with mitapivat. In both trials, mitapivat improved other clinical parameters of haemolysis and patient-reported health-related quality of life. At the approved twice-daily dosage range, mitapivat was generally well tolerated, with adverse events generally being mild to moderate in severity. Results from an ongoing extension study in previously enrolled phase III trial patients will be of interest. Currently available data indicate that mitapivat, the first approved disease-modifying drug for PK deficiency in adults, is a valuable treatment option for this rare disease.

Pyruvate kinase (PK) deficiency is a rare hereditary disease caused by mutations affecting the function of the PK enzyme in red blood cells (RBCs) and is characterized by chronic haemolytic anaemia. Treatment options for adults with PK deficiency have historically been limited to supportive care and are themselves associated with potentially serious complications. Oral mitapivat (Pyrukynd^®) is the first disease-modifying drug to be approved for use in adults with PK deficiency and acts by restoring activity of the dysfunctional RBC PK enzyme. Based on findings from two phase III clinical trials, twice-daily oral mitapivat provided clinical benefit in adults with PK deficiency, both in patients not requiring, and requiring, regular RBC transfusions. Improvements in disease-specific health-related quality of life were observed in adults with PK deficiency treated with mitapivat. Mitapivat was generally well tolerated, with most adverse events being mild to moderate in severity. In conclusion, current evidence indicates that mitapivat is a valuable treatment option for adults with PK deficiency.