Dexamethasone

Quince Therapeutics will cease clinical development of eDSP and “[i]ntends to preserve cash and explore available options,” the company said in a Jan. 29 release. Quince Therapeutics’ novel method of delivering steroids in a patient’s own red blood cells has turned out to be a bust in ataxia-telangiectasia (A-T), a rare inherited disorder.A pivotal phase 3 trial of the company’s lead asset, dexamethasone-containing eDSP, has failed to meet both its primary and secondary endpoints, Quince said late this week. The company’s stock price on Nasdaq plummeted more than 90% on the news, closing at $0.27 per share Thursday.Quince will cease clinical development of eDSP and “[i]ntends to preserve cash and explore available options,” the company said in a Jan. 29 release.As of the end of September, Quince had cash, cash equivalents and short-term investments of $26.3 million, which the company expected could support its operations into the second quarter of 2026, according to its third-quarter report. A-T, also known as Louis-Bar syndrome, is a rare genetic disease that affects the nervous system and the immune system. Caused by mutations in the ATM gene, the disease begins in early childhood with the first signs being unsteady movements and poor coordination (ataxia). Another main characteristic of the condition is small clusters of dilated blood vessels in the eyes and on the skin (telangiectasia). Most patients with the condition live up to 30 years of age as infections and cancer develop. Citing IQVIA data, Quince noted that about 4,600 patients are diagnosed with A-T in the U.S.No approved therapeutic treatments currently exist for A-T. Corticosteroids such as dexamethasone have shown some benefits in improving neurological functioning in A-T, but their long-term use is limited by toxicity.Quince developed eDSP, also known as EryDex, using its autologous intracellular drug encapsulation (AIDE) platform. The technology involves harvesting a patient’s own red blood cells, adding dexamethasone sodium phosphate through the cells’ porous membranes, and using hypertonic solutions so the cells can encapsulate the drug for administration back into the patient. Dexamethasone is then expected to be slowly released into circulation. The goal is to reduce toxicity related to frequent high dose treatment with steroids, while maximizing drug exposure to maintain its anti-inflammatory effects.To test eDSP in A-T, Quinch launched the placebo-controlled phase 3 Neat study, which enrolled 105 patients, including 83 6- to 9-year-olds in the primary analysis population. Patients were given six infusions scheduled once every 21 to 30 days. The trial’s primary endpoint evaluated patients’ change from baseline to last efficacy visit at Month 6 using the Rescored modified International Cooperative Ataxia Rating Scale (RmICARS) between eDSP and placebo.The study did not meet that endpoint, as the mean change was 0.94 for eDSP and 2.24 for placebo, with a p-value of 0.0851. A higher RmICARS score indicates greater disease severity of ataxia impairment.The study was powered at approximately 90% to test for a statistically significant difference between eDSP and placebo on the primary endpoint, Quince’s CEO and chief medical officer, Dirk Thye, M.D., said in the company’s third-quarter report in November. At that time, Thye expressed confidence in a successful readout, citing a go-ahead from an independent data monitoring committee following a safety analysis and all trial participants’ decision to enroll in an open-label extension study.On the trial’s secondary endpoint of improvement in Clinical Global Impression of Severity, also measured from baseline to Month 6, the p-value was 0.522, which, again, was not statistically significant.“eDSP was generally well tolerated and there were no clinically meaningful safety concerns identified,” Quince said. Neat was launched after another phase 3 trial, Attest, failed to show a benefit for Quince’s intra-erythrocyte approach in a wide age group. But a subgroup analysis found that children ages 6 to 9 years appeared to benefit from a high dose of the drug. In addition, the study authors also cited the pandemic as a possible reason for the flop, as many patients had delayed or missed treatments.

Quince Therapeutics’ once-monthly steroid-based treatment failed a Phase 3 trial for a rare genetic condition called ataxia-telangiectasia, prompting the Bay Area company to say it would stop development of the experimental product. Thursday’s announcement walloped the company’s shares $QNCX , which were down more than 90% on Friday morning compared with Wednesday’s close. Quince’s therapy, called eDSP, involves a machine that uses some of a patient’s own blood, encapsulating the steroid dexamethasone into blood cells that are then administered back to the patient. The approach was meant to mitigate the side effects of daily steroid treatment. However, in a Phase 3 study with 105 patients, Quince’s treatment did not significantly improve scores at six months compared to placebo on a measure of disease called the RmICARS. The measure primarily examined a patient’s posture and gait. Quince said that the difference in average change in the two arms on the RmICARS was -1.30, with a p-value of 0.0851. In addition, the study failed to meet a key secondary endpoint — the Clinical Global Impression of Severity. Quince’s pivotal trial failure in ataxia-telangiectasia comes one week after IntraBio said its treatment for the disease succeeded. IntraBio is developing a drug called Aqneursa, which is a modified version of leucine, and plans to submit its application to the FDA for ataxia-telangiectasia in April. Ataxia-telangiectasia is a progressive disease that starts in childhood and whose name describes its key symptoms: ataxia — a loss of muscle control — and telangiectasias — tiny red blood vessels that appear on the skin. But the disease can affect many functions of the body, including the immune and nervous systems. With its decision to stop work on its treatment, Quince said it “intends to preserve cash and explore available options.”