Phase 3 rare disease flop leaves Diurnal reeling

Diurnal CEO Martin Whitaker (Diurnal)

Diurnal’s Chronocort has failed to beat the control in a phase 3 congenital adrenal hyperplasia (CAH) trial. The modified-release preparation of hydrocortisone was no better at controlling sex hormones than conventional glucocorticoid doses, sending Diurnal’s stock into a downward spiral.

U.K.-based Diurnal designed Chronocort to be a cortisol replacement for people whose bodies are unable to produce enough of the metabolic hormone, including patients with the rare autosomal recessive disorder CAH. These patients suffer from an enzyme deficiency that can lead to death if not treated. Today, glucocorticoids are prescribed to replace cortisol.

Diurnal thought it could improve on glucocorticoids by developing a drug with a release profile that hews more closely to the daily rhythm of cortisol release in healthy individuals. That hypothesis is on the ropes.

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For the phase 3, Diurnal enrolled 122 CAH patients and randomized them to either continue on their standard-of-care regimes or switch to twice-daily doses of Chronocort. Over 24 weeks, investigators analyzed the change in levels of 17-hydroxyprogesterone, a steroid hormone that builds up in the blood in CAH patients. Chronocort was no better than glucocorticoids at controlling the hormone.

News of the finding wiped 58% off the stock price of Diurnal and left Chronocort facing an uncertain future. Diurnal will discuss the data, plus interim findings from an ongoing long-term dosing study, with regulators before reconsidering its European approval aspirations and pivotal U.S. trial.  

Management is going into the talks armed with some glimmers of hope. Subjects in the Chronocort arm achieved control on a lower overall dose of glucocorticoid, required less rescue therapy and were free from the early-morning peak in androgen levels experienced by participants who received conventional therapy.

Diurnal CEO Martin Whitaker focused on these positives in his discussion of the data

“We are surprised by these results, following our previously successful phase 2 clinical trial in CAH,” Whitaker said in a statement. “However, these initial results confirm the concept of Chronocort, that early morning control of androgens can be achieved with a modified release preparation of hydrocortisone. We remain confident that Chronocort will be a valuable treatment option for CAH patients.”