the prescriptions but 30% or $7bn in dollar sales. The market is filled with generic drugs (about 83% of the total opioids) but that is mainly because 98% of the IR opioids are generics. Among ER opioids, 28% of the drugs are branded but more than 50% of the sales are generated from the branded drugs.
Opioid drug abuse and Abuse Deterrent Opioids (ABO):
The most common method to abusing the drugs other than taking multiple pills would include i) physical manipulation – chewing, crushing, or grinding pills that can lead to higher rate of absorption, ii) Extraction/dose-dumping, and iii) non- oral administration – drug is delivered through alternative sources for rapid absorption such as snorting, smoking, or intravenous injection.
FDA over the last few years has taken a number of steps to fight the abuse of these drugs. FDA has been promoting drug manufacturers to develop abuse-deterrent opioids (ADO) and has been reviewing most cases on a priority basis for expediting the approvals.
ADO are developed such that they are not easily manipulated by the users. The typically properties of ADO’s include i) Hard to crush – hard shell or coating that makes it difficult to crush, ii) agonist/antagonist – these drugs contain opioid antagonist that are released upon tampering that negate the effect of the opioid, iii) Irritants – irritants are released upon tampering, and iv) Prodrugs – drugs that active only when they are in the digestive tract.
ADOs market was about $2.6bn in 2015, 37% of total ER sales (or 75% of the branded ER sales) and 4.1mmTRx’s (21% of total ER TRx’s) according to Symphony Health Solutions. With only 21% of the current prescriptions been ADOs, the market has substantial room to grow (at least another $1bn as the entire branded drugs are ADO prescribed). Oxycotin (manufactured by Purdue Pharma) currently dominates this market. XTAMPZA would be mainly competing for this market share.
XTAMPZA – properties and competitive advantages of the drug:
XTAMPZA was approved by the FDA in April 2016 and the drug was launched in the market on June 20, 2016. Collegium uses its DETERx technology to develop the drug that mixes the active ingredient with other substances to form microcapsules. Each capsule is made of these microcapsules making further crushing difficult. Capsules contain microspheres formulated with inactive ingredients intended to make the formulation more difficult to manipulate for misuse and abuse. You could read more about the technology on the Company’s website here http://www.collegiumpharma.com/technology/overview
The following studies were conducted by the FDA during the Phase 3 trials:
1) Vitro (Lab) Testing: Vitro physical and chemical manipulation studies were performed to evaluate the success of different methods of defeating the extended-release formulation. Results suggested that the capsules are less susceptible to the effects of grinding, crushing, and extraction using a variety of tools and solvents. The capsule also resisted attempts to extract and pass into needles through suspending the microcapsules in water.
2) Pharmacokinetic Studies (PK testing): PK profile of the manipulated capsule (Crushing, chewing, etc) that was administrated separately through oral and intranasal was studied and compared with IR Oxycodone. PK profile studies measure the blood levels of the drug over time for Higher Maximum concentration (Cmax) and shorter time to peak concentration (Tmax). Below Table 3 and Table 4 show the results of the studies. The results were amazing with XTAMPZA showing bioequivalence between manipulated and intact formulations, and the manipulated drug actually showed lower Cmax and higher Tmax compared to the intact drug, implying lower risk of abuse. While XTAMPZA was significantly better than the Oxycodone comparator used for testing, no other approved ADO drugs have shown these kind of results in clinical studies.
3) Clinical Abuse Potential testing: Oral and nasal abuse trials are conducted for Drug-liking and Take-drug Again tests. Studies are randomized, double-blind, placebo controlled where recreational abusers determine how much they like/dislike a drug. For oral administration, FDA reported that while the Drug Liking score was lower than IR Oxycodone, the results of the Take Drug Again tests were small and not statistically significant. Table 5 and Table 6 show the results of the oral and intranasal studies.