Treatment of opioid dependence

Zubsolv is a product for the treatment of opioid dependence. Zubsolv is based on Orexo’s broad knowledge of sublingual (under the tongue) preparations. The new product will offer a number of advantages compared with the present market leader, Suboxone®.

Active ingredients and advantages

Just like its competitor Suboxone, Zubsolv consists of a combination of buprenorphine and naloxone. The active ingredient, buprenorphine, has documented good efficacy in the treatment of opioid dependence. It eases withdrawal symptoms at the same time as it blocks the “high” effects of other opioids.

Combining buprenorphine and naloxone (an opioid antidote) in a single tablet counteracts the “high” effect that may arise following inappropriate intravenous injection of a dissolved tablet. The risk of intravenous abuse is thereby reduced.

Through application of its proprietary technologies, Orexo has increased the bioavailability of the active ingredients, accelerated dissolve time, reduced tablet size and improved the taste. Preference for Zubsolv has been compared with Suboxone® Tablet and Suboxone® Film in two independent studies. Key results from these studies show that the subjects in the trials preferred Zubsolv over the competitors (80-90 percent in favor of Zubsolv). Important parameters are improved taste, mouth-feel and ease of administration.

Market potential

Zubsolv is expected to be the first improved branded competitor to Reckitt Benckiser’s product Suboxone®, which reached sales of USD 1.5 billion in the USA during 2012. Suboxone grew by over 20% in the USA during 2012. Zubsolv is assessed to have great market potential, as the product’s unique properties, which have been confirmed during the studies performed, are expected to lead to increased acceptance by patients.

A preference study that was completed in June 2012 compared Zubsolv and Suboxone® Tablet and demonstrated that 9 out of 10 participants preferred Zubsolv. In November, Orexo completed a study to assess acceptance of Zubsolv compared to Suboxone® Film. The study was a cross-over trial in which 28 participants were given either Zubsolv or Suboxone Film in random order on separate study days. Key results indicate that Zubsolv was preferred by 9 out of 10 participants on all acceptance parameters tested, i.e. overall acceptability, taste masking, after taste experience, mouth-feel, and ease of administration. When asked specifically about which product the participants would choose for daily treatment, 9 out of 10 participants reported that they would select Zubsolv.

Reckitt Benckiser Ltd has announced that they intend to discontinue distribution of Suboxone® in tablet form in the USA during the first quarter of 2013. Suboxone will thereafter only be available from Reckitt Benckiser as a film in the USA creating yet another commercial opportunity for Zubsolv. In late February 2013, the FDA informed that two generics to Suboxone Tablet have been approved.

Based on the increasing medical and non-medical use of prescription opioid products in the USA, Orexo estimates that the American market for the treatment of opioid dependence will continue to grow and that in 2014 it will be worth USD 2 billion. In addition to this, the number of patients actually seeking treatment for opioid dependence has increased and data suggests that the treatment time for these patients is increasing. It is estimated that more than 5 million Americans are dependent on opioids. Just under 10 percent of these patients receive adequate treatment.

The societal cost of opioid dependence is today estimated to USD 55 billion, of which USD 25 billion are healthcare-related costs. According to the Institute of Addiction Medicine the health economic gains from the treatment of opioid dependence may be twelve times the cost of the treatment. Awareness of the gains from treatment is increasing all the time within healthcare.

Orexo assesses that Zubsolv’s chances of success on the market are high given the unique properties of the product in a rapidly growing market with major underserved medical needs. The company estimates that the market potential of the product is in excess of MUSD 500 in annual sales.

Project status

During 2012, a number of important studies were completed with positive results. A dose proportionality study documented the expected bioavailability of buprenorphine and naloxone with increasing doses of Zubsolv. In another study Zubsolv was tested and compared with the market-leading product, Suboxone®, and the results displayed the same bioavailability for both products.

In September 2012, a New Drug Application was submitted in the USA to the U.S. Food and Drug Administration, FDA.
This occurred several months earlier than estimated. Beside the positive results from the two previously mentioned studies, the time gained was due to the fact that it was possible to use the product stability data from our production site in Uppsala in the registration. In addition to the work at our production site in Uppsala, a production unit is being built up in the USA in collaboration with Orexo’s CMO (Contract Manufacturing Organization).

In November the FDA gave notification that the New Drug Application for Zubsolv had been accepted for review. The planned date for notification of approval is July 6, 2013. If this time plan is followed, it is planned that the product will be launched in September 2013.

During the fourth quarter a comparative acceptance study between Zubsolv and Suboxone® Film was completed. The study showed that 9 out of 10 participants would choose Zubsolv rather than Suboxone Film for daily treatment.

In parallel with the New Drug Application in the USA, Orexo is working on further developing Zubsolv. Clinical studies will be initiated during the first half of 2013 in order to investigate whether it is possible to use Zubsolv upon initiation of treatment, how well patients comply with the Zubsolv treatment, and health economic aspects. The broad development program also includes, amongst other things, the development of new strengths and a new flavor.