TQ-1028 (Oral Extended Release Buprenorphine Tablets)
TQ-1028 is a proprietary once-a-day oral extended release (ER) dosage form of the Schedule III (C-III) opioid, buprenorphine. Buprenorphine ER is being developed for the treatment of chronic moderate to moderately severe pain and opioid dependence.
We believe Buprenorphine is a superior alternative to the Schedule II (C-II) opioids (e.g., oxycodone, hydromorphone, oxymorphone and morphine), in terms of improved safety, lower DEA schedule, and reduced risk of physical dependence, addiction and drug diversion. We have developed robust oral extended release dosage forms of buprenorphine suitable for once-daily administration.
Buprenorphine has been widely used by the sublingual and transdermal routes of administration. However, heretofore, buprenorphine was believed to be ineffective by the oral route. TheraQuest has made important discoveries about the analgesic efficacy of oral buprenorphine in validated animal models of nociception and in patients with clinical pain. We have demonstrated that oral buprenorphine provides:
- Robust antinociception in a variety of validated pain models
- Pain relief In patients with musculoskeletal pain
- Superior pain relief after ileal and colonic delivery than after gastric delivery
Oral Buprenorphine is Analgesic
Radiant Heat Tail Flick Model of Analgesia
Targeted Ileo-Colonic Delivery of Buprenorphine
Superior Analgesia Compared to Gastric Delivery*
Rationale for Buprenorphine ER
Buprenorphine’s unique pharmacology distinguishes it from the full μ-opioid receptor agonists. Among its advantages over oxycodone, oxymorphone, morphine and hydromorphone (the active opioids in OxyContin®, Opana® ER, Embeda®, and Exalgo®, respectively) are:
- Ease of prescribing C-III instead of C-II;
- Reduced risk of physical dependence;
- Significantly lower “drug liking” by opioid addicts and recreational users; and
- Reduced risk of respiratory depression in overdose.
TQ-1028 will compete in the same opioid pain market segment as OxyContin®, Opana® ER, Embeda®, Kadian®, Avinza® and Exalgo® (2009 U.S. opioid sales $8.5 billion), with the advantage of C-III prescribing status and reduced risk of drug abuse. Additionally, TQ-1028 will compete with sublingual buprenorphine (Suboxone®/Subutex®) and methadone for the treatment of opioid dependence (2009 sales for sublingual buprenorphine were $970 million).
Advantages of C-III Scheduling
According to FDA and DEA, buprenorphine has a lower potential for abuse relative to C-II opioids such as oxycodone, oxymorphone, morphine and hydromorphone (http://tinyurl.com/yfmcjbn; http://tinyurl.com/2cxnzxp), the opioids in OxyContin®, Opana® ER, Embeda®, and Exalgo®, respectively”. This lower abuse potential includes a reduced risk for physical dependence and reduced “liking” by recreational drug users.
In addition to the lower risk of opioid abuse, C-III opioids have prescribing advantages over C-II opioids. Prescriptions for C-II drugs must be written and they cannot be refilled. In contrast, prescriptions for C-III drugs may also be transmitted by phone and fax and they may be refilled 5 times in 6 months. Given a choice, we believe clinicians are more likely to use C-III extended release opioids over C-II extended release opioids, particularly for moderate to moderately severe pain. There are currently no marketed C-III extended release opioids in the United States.
Oral Extended Release Buprenorphine
Advantages of a C-III Opioid Analgesic
What others are saying about buprenorphine …….
Food and Drug Administration (FDA): “Buprenorphine is considered to have less risk for causing psychological and or physical dependence than the drugs in Schedule II such as morphine, oxycodone, fentanyl, or methadone” (FDA Press Release, http://tinyurl.com/yfmcjbn)
International Expert Panel (2009): "when compared with morphine, hydromorphone, oxycodone, fentanyl and methadone, buprenorphine is “the top-line choice for opioid treatment in the elderly” (Pergolizzi et al, Pain Practice, 2008;8:287-13, http://tinyurl.com/yggvj5f).
National Institute on Drug Abuse (NIDA): “ . buprenorphine is less likely to cause respiratory depression, the major toxic effect of opiate drugs, in comparison to full agonists such as morphine or heroin. We believe this will translate into a greatly reduced chance of accidental or intentional overdose. Another benefit of buprenorphine is that the withdrawal syndrome seen upon discontinuation with buprenorphine is, at worst, mild to moderate and can often be managed without administration of narcotics.” (Buprenorphine Update: Q&A, http://tinyurl.com/28zqjhe).
Substance Abuse and Mental Health Services Administration (SAMHSA): “…. buprenorphine carries a lower risk of abuse, addiction, and side effects compared to full opioid agonists” (About Buprenorphine Therapy, SAMHSA, http://tinyurl.com/y5hhe63).
Buprenorphine Extended Release Dosage Forms
TheraQuest has developed several robust, proprietary formulations of extended release buprenorphine (Buprenorphine ER) suitable for dosing once-a-day for the treatment of pain & opioid dependence. The release profile of two sample dosage forms, one an extended release matrix tablet and another an osmotic push pull dosage form are provided below.
Matrix Buprenorphine ER Oral Once-a-Day Tablets
Sample Release Profile Over 24 Hours
Osmotic (Push-Pull) Buprenorphine ER Once-Daily Tablets
Consistent 24 Hour Zero-Order Release Across Three Batches
Intellectual Property and Market Exclusivity
TheraQuest has filed two methods of use and pharmaceutical composition patent applications for oral buprenorphine ER. In the E.U, we believe Buprenorphine ER will be eligible for 10-year data exclusivity. We intend to cement our market exclusivity through additional patents based on the pharmaceutical and clinical characteristics of our drug and through the introduction of line extensions with non-opioids.