Limitations of Current Medication-Assisted Treatments

Quadra Therapeutics is a 501(c)(3) nonprofit pharmaceutical company with a mission to develop and expand access to quality medicines for Opioid Use Disorder (OUD) for all patients, regardless of their socioeconomic status, insurance or geography. Although three drugs (buprenorphine, methadone and naltrexone) are approved for MAT, treatment adherence, overall abstinence and long-term efficacy are suboptimal.

  • Methadone is proarrhythmic and associated with long QT syndrome, leading to potentially lethal ventricular tachyarrhythmias, torsades de pointes and sudden death. Methadone is also a full μ-opioid receptor agonist and therefore carries a greater risk of death in overdose settings.
  • Naltrexone does not control symptoms of withdrawal or reduce craving, so it is only appropriate for relapse prevention in opioid abstinent patients. Oral naltrexone is no longer recommended due to low patient acceptance and retention, and high rates of nonadherence.
  • Sublingual buprenorphine also has limitations, including: (i) low adherence and treatment retention; (ii) significant diversion into the illicit drug market; (iii) accidental poisoning; and (iv) high relapse. In one study, relapse was 10x greater when adherence was ≤80%. In addition, there were >8,100 emergency department visits by children ≤ 6 yr with 62% needing hospitalization due to sublingual buprenorphine between 2008-2015. Finally, buprenorphine can also result in long QT syndrome at high doses when used with other drugs that prolong the QT interval.
  • Extended-release (depot) MATs, naltrexone and buprenorphine virtually eliminate the risk of diversion and accidental poisoning, and remove the burden of daily adherence, although each carries significant limitations
  • Depot naltrexone (Vivitrol®) must be given as a monthly gluteal injection. It does not control symptoms of withdrawal or reduce craving and is suitable only for a minority of patients who are both highly motivated and abstinent.

Probuphine® and Sublocade® are two marketed depot buprenorphine MATs. Probuphine® is a 6-month subdermal surgical implant suitable only for patients with very low dose (≤ 8mg/day) buprenorphine requirements and requires surgical removal and replacement. Sublocade® is a monthly subcutaneous depot buprenorphine which shows 90% abstinence and study completion only in 24%, and 62% of patients respectively, and injection site reactions in 14-and 19% at low and high doses. Additionally, it is not room temperature stable, and it can only be given at one of two dose levels monthly through a 19 Gauge needle into abdominal subcutaneous tissue.

QTX-4032: Our Lead Program Using Depotrol Technology

In view of the limitations of currently available MATs, Quadra Therapeutics is developing next generation treatments using Depotrol™ technology to provide improved patient and clinician acceptance, and both short-and long-term treatment outcomes in patients. Our lead MAT is QTX-4032 which is pharmaceutically and pharmacologically differentiated from Sublocade®.

Pharmaceutical Differentiation: QTX-4032 holds the promise of (i) weekly, biweekly and monthly dosing options at a wide range of doses to individualize treatment; (ii) room temperature stability to reduce storage costs and logistics, particularly in low and middle-income countries; and (iii) injection into any subcutaneous tissue with a 50% thinner needle bore.

Pharmacological Differentiation: QTX-4032 holds the promise of improved short-and long-term outcomes through different mechanisms of action, when compared with currently available depot dosage forms.