Titration kit for starting on Austedo well-received by patients in trial

Oral therapy is approved in US for chorea in Huntington's disease

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A four-week titration kit for starting on Austedo (deutetrabenazine) — an approved therapy for chorea, or involuntary muscle contractions, due to Huntington’s disease — has so far been well-received by patients in a Phase 4 clinical trial.

Titration, in medicine, means starting a drug at a low dose and then increasing the dosage over a specified period of time until the maximum effective one without significant adverse effects is being given.

Teva Pharmaceuticals, the company that sells Austedo, presented early trial findings on its use of these titration kits among Huntington’s patients in a poster at the 30th Annual Meeting of the Huntington Study Group (HSG), held Nov. 2-4 in Arizona.

“Through our discussions with the HD [Huntington’s disease] community, we understand the importance of providing treatment options that are not only safe and effective but set patients up for success by ensuring treatment regimens are manageable and tolerable,” Eric Hughes, MD, PhD, executive vice president of global research and development and chief medical officer at Teva, said in a company press release.

“We’re excited to share this latest data with the scientific community, further supporting that Austedo is an effective treatment option for patients with HD chorea,” Hughes added.

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All patients reported ease of use of titration kit

Chorea is a hallmark symptom of Huntington’s that’s characterized by uncontrolled jerking or writhing movements. Austedo is an approved oral treatment that works to manage this symptom in adult patients by modulating the activity of a protein called VMAT2.

Austedo XR, an extended-release version of the medication that is taken once a day instead of twice daily, became available in the U.S. earlier this year. Both formulations also are approved in the U.S. for the treatment of adults with tardive dyskinesia, another movement disorder marked by chorea.

Both the standard and extended-release formulations of Austedo are started at a low daily dose (12 mg) that is then titrated, or gradually adjusted, up to a maximum of 48 mg per day, based on efficacy and tolerability.

Teva is running a Phase 4 clinical trial — one conducted after a drug has been approved for use — to test a four-week titration kit for Austedo. Called START, the study guides Huntington’s and tardive dyskinesia patients through the first four weeks of dose titration, starting at a dose of 12 mg/day that is increased up to 30 mg/day by week four.

At the HSG meeting, Teva presented interim data from the first 17 Huntington’s patients in the trial. Nearly three-quarters of these patients (71%) successfully completed the titration kit, and nearly all (92%) achieved a maintenance dose of at least 24 mg/day.

After 12 weeks, or about three months, of treatment, nearly two-thirds of participants (63%) reported reductions in patient-rated measures of overall disease severity. About half showed reductions in similar clinician-rated measures. Total maximal chorea severity scores dropped by an average of 41%.

With 90% of [Huntington’s] patients developing chorea, it’s critical that treatment options can address the unmet needs of this community.

All patients who completed a survey about the titration kit said it was easy to use.

“With 90% of HD patients developing chorea, it’s critical that treatment options can address the unmet needs of this community,” said Karen Anderson, MD, a professor at Georgetown University School of Medicine and director of the Huntington’s Disease Care, Education and Research Center.

“These data reinforce that in real-world settings the Austedo 4-week Patient Titration Kit enabled patients to titrate to therapeutic Austedo doses with satisfaction, adherence, and effectiveness similar to results demonstrated in the pivotal clinical trials,” Anderson added.

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Ingrezza now approved by FDA for chorea in Huntington’s disease

Austedo, Austedo XR, Ingrezza all approved in US to treat chorea

Teva also presented a separate poster that included data from seven Huntington’s patients who switched to Austedo from an older chorea treatment Xenazine (tetrabenazine) due to inefficacy. Chorea scores were generally reduced following the switch, and no unexpected safety issues were reported, according to the company.

A third poster at HSG included analyses of Austedo, Xenazine, and Ingrezza (valbenazine) — the most recently approved chorea treatment in the U.S.  All three therapies target the VMAT2 protein.

Data showed that, for all three medications, the number needed to treat ranged from three to four for clinical-rated disease measures and from four to five for patient-rated measures.

This meant that, statistically, about 3-5 patients would need to be treated with the medication for an additional patient to see a chorea reduction when they would not otherwise have achieved that outcome without the treatment. 

The researchers also calculated the number needed to harm, which reflects how many patients would need to be given a therapy before it’s statistically probable that someone will experience an unwanted side effect when they would not otherwise have been harmed.

The only significant side effect reported for Austedo in these analyses was diarrhea, according to Teva. Notable side effects for Ingrezza included sleepiness, lethargy, sedation, hives and rash, while for Xenazine these were sleepiness, insomnia, worse anxiety, balance problems, slowed movements, and restlessness.

“Together, the data provide additional insight into the real-world efficacy and safety of Austedo for patients with HD chorea,” Teva stated in the release.