FDA Drug Approvals, Endocrinology — 2020 Midyear Review

August 14, 2020

Dojolvi (triheptanoin)

Triheptanoin is indicated as a source of calories and fatty acids for molecularly confirmed long-chain fatty acid oxidation disorders (LC-FAODs) in adults and children. It is a medium-chain triglyceride consisting of 3 odd-chain 7-carbon-length fatty acids (heptanoate) that provide a source of calories and fatty acids to bypass the LC-FAOD enzyme deficiencies for energy production and replacement.

For this rare disease, a small double blinded, randomized controlled trial of 32 subjects with LC-FAODs (carnitine palmitoyltransferase-2, very long?chain acylCoA dehydrogenase, trifunctional protein, or long-chain 3-hydroxy acylCoA dehydrogenase deficiencies) were randomly assigned a diet containing 20% of their total daily energy from either triheptanoin or trioctanoin. At 4 months, patients in the triheptanoin group increased left ventricular (LV) ejection fraction by 7.4% (P=.046) while experiencing a 20% (P=.041) decrease in LV wall mass on their resting ECG. They also required a lower heart rate for the same amount of work during a moderate-intensity exercise stress test when compared with patients taking trioctanoin.

( J Inherit Metab Dis 2017 Nov;40(6):831-843)

Isturisa (osilodrostat)

Osilodrostat is an orally administered steroidogenesis inhibitor of 11-beta-hydroxylase, an enzyme that catalyzes the final step of cortisol synthesis in the adrenal cortex. It is indicated for Cushing disease in adults for whom pituitary surgery is not an option or has not been curative.

Approval of osilodrostat was based on the phase 3 LINC-3 clinical trial (n=137). It was a multicenter, double-blind, randomized withdrawal study following a 24-week, open-label, single-arm treatment phase. Open-label osilodrostat was initiated at 2 mg twice daily in 137 adults with Cushing disease and mean urinary free cortisol (mUFC; mean of three 24-h samples) greater than 1.5 times the upper limit of normal (ULN) (ULN=50 mcg/24 h), with dose adjustments every 2 weeks (dose range 1-30 mg BID) up to week 12 based on efficacy (if mUFC > ULN) and tolerability. At week 26, 71 eligible patients (mUFC equal to or below ULN at week 24 without a dose increase after week 12) were randomized to continue osilodrostat (n=36) or matching placebo (n=35) for 8 weeks, followed by open-label osilodrostat until week 48. Patients who remained on treatment at week 26, but were not eligible for randomization, continued open-label osilodrostat (n=47).

At baseline, median (range) mUFC was 3.5 times the ULN (0.3-69.6) in enrolled patients. At the end of the randomized withdrawal period (week 34), significantly more patients maintained mUFC equal to or less than the ULN (without a dose increase after week 26) in the osilodrostat group than in the placebo group (86% vs 29%; odds ratio, 13.7; P <.001).

( J Endo Soc 2019 Apr-May;3(1; Suppl)

Other endocrinology approvals

Gimoti (metoclopramide intranasal) - New dosage form for symptomatic relief of acute and recurrent diabetic gastroparesis.

Qutenza (capsaicin transdermal) - New prescription-strength transdermal patch for neuropathic pain associated with diabetic peripheral neuropathy of the feet.

Trulicity (dulaglutide) -Indicated for primary and secondary risk reduction of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease or multiple risk factors.

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