CHICAGO – Mifepristone therapy for Cushing’s syndrome provides an important side benefit: clinically meaningful weight loss that persists over time.
That’s a key finding from the long-term extension phase of the SEISMIC study, a 24-week, multicenter study that led to Food and Drug Administration approval of mifepristone (Korlym) in 2012 as the first and only medication indicated for the treatment of endogenous Cushing’s syndrome.
In the long-term extension phase of the SEISMIC study, mifepristone therapy for up to 3.5 years was associated with a mean 9.3% weight loss from baseline, Dr. Henry G. Fein reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.
Of patients who lost at least 5% of their body weight during the initial 24-week treatment period in the SEISMIC study, 83% maintained that amount of weight loss through the long-term extension phase. A sustained weight loss of that scope is likely to translate into a reduced risk of cardiovascular disease and metabolic dysfunction, said Dr. Fein of Johns Hopkins University, Baltimore.
Endogenous Cushing’s syndrome is a rare disease, and the phase III SEISMIC study (J. Clin. Endocrinol. Metab. 2012;97:2039-49), while pivotal, was small, involving 50 patients treated with the glucocorticoid receptor antagonist at 300-1,200 mg once daily for 24 weeks. Afterward, 29 patients underwent a 6-week period off drug for safety assessment and then went back on mifepristone for a median of 29.2 months and a maximum of 3.5 years in the extension study.
At baseline, the mean body weight in these 29 patients was 105.4 kg. It dropped to 97.2 kg by week 24. Six weeks later, when patients went back on mifepristone, their mean weight was 98.6 kg. At last follow-up – with patients still on the drug – their mean weight was 95.1 kg, a 9.3% decrease from baseline.
Eighteen of 29 patients achieved a 5% or better weight loss by week 24; at the most recent follow-up, 15 of the 18 (83%) maintained or improved upon that degree of weight loss. Moreover, of the 10 patients who lost at least 10% of their body weight during the first 24 weeks of treatment, 8 maintained that amount of weight loss by study’s end.
Surgery is accepted as the treatment of choice for most patients with Cushing’s syndrome. However, various studies have shown that 10%-45% of surgically treated patients have persistent or recurrent hypercortisolism postoperatively, with accompanying weight gain. That’s where mifepristone plays a key role. In addition, the drug is valuable in patients who aren’t surgical candidates, the endocrinologist noted.
Mifepristone was formerly known as RU-486, "the abortion pill."
The SEISMIC study and its long-term extension were funded by Corcept Therapeutics. Dr. Fein is on the company’s speakers bureau.