Strong positive phase III results earlier this month for Alkermes’ Vivitrol in opioid dependency, following its marketing approval in alcohol dependency in 2006, not only bodes well for eventually approval of the drug, potentially in 2011, but should provide a much needed new product in the fight against opioid abuse and addiction.
In a six month trial of Vivitrol, patients who had recently come off opioids and were receiving Vivitrol injections once a month achieved significantly higher rates of clean, opioid free, urine screens than those on placebo. The study also met its secondary end points of retaining patients and reducing cravings for opioids. But following the triumph of Vivitrol, as the table below shows, there are few other late stage products in the opioid addiction space.
An analysis of the space by EP Vantage points to the fact that innovation is not a key focus of the market, that has so far been dominated by Reckitt Benckiser and Merck & Co’s Subutex and Suboxone, which between them last year chalked up sales of $266m.
The lack of new products to challenge the old guard is shown by the fact that despite its patent expiring in October of this year, sales of Subutex are expected to hold up relatively well, rising from $214m this year to $225m by 2014. This is mainly due to the fact that there has yet to be a generic challenge to the drug, something that could say more about drug developers’ view of the space rather than any lack of opportunity.
What should help Vivitrol compete against the two entrenched products is the fact that they are both based on buprenorphine, a partial opioid agonist, which itself produces a small high, thus its appeal as a drug to wean addicts off opioids.
But this has meant that the FDA has classified the drugs as Schedule III, underlining their potential abuse risk and also calling for tighter procedures regarding their prescription. As an opioid receptor antagonist, the opportunity for abuse with Vivitrol is much lower. This and the drug’s high efficacy should give it enough to differentiate itself in the market if it gets approval and enable it to steal some market share from Subutex and Suboxone. Additionally, the small number of doctors operating in this end of the field should mean that Alkermes is more than capable of commercialising the product itself.
Alkermes is aiming for a filing on a sNDA by the middle of next year, potentially leading to approval in the first half of 2011.
The rest of the field
The closest rival snapping at Vivitrol’s heels is probuphine. Rather than being a daily oral pill or monthly injection, probuphine is a long-acting implant consisting of buprenorphine, that provides a constant, low level of the drug for six months. Titan Pharmaceuticals is hoping this approach will overcome one of the biggest problems with opioid addiction, compliance to treatment.
Camurus is also focused on cracking the tricky problems of compliance and its phase II drug, CAM2038, is an injectible formulation of of buprenorphine. Given that it may have to be taken weekly, Vivitrol is several steps ahead of it and Titan’s drug last for six months after initial treatment, if it does get the market CAM2038 could struggle to put on sales.
Of the other proprietary products waiting in the wings many have opioid dependency as their second or third indication. One example, Avigen’s AV411, is primarily being developed in neuropathic pain. Roche and Synosia Therapeutics have decided to focus their main efforts for SYN-115 on the more lucrative market of Parkinson's Disease, with opioid addiction coming a poor third after cocaine addiction. Similarly, SYN-117’s primary indication is cocaine addiction.
|Opioid Addiction Products|
|Annual Sales WW - ($m)|
|Marketed||Subutex||Merck & Co/ Reckitt Benckiser||Opioid agonist||34||218||222||225|
|Suboxone||Reckitt Benckiser/ Merck & Co||Opioid agonist & opioid antagonist||232||60||27||27|
|Revia||Teva Pharmaceutical Industries||Opioid antagonist||4||4||4||4|
|Phase III||Vivitrol||Alkermes/Johnson & Johnson||Opioid antagonist||21||26||34||69|
|Probuphine||Titan Pharmaceuticals||Opioid agonist||-||-||-||-|
|Phase II||AV411||`||Glial cell modulator||-||-||-||-|
|OX219||Orexo||Opioid agonist & opioid antagonist||-||-||-||-|
|Phase I||SYN-115||Roche/Synosia Therapeutics||Adenosine A2A receptor antagonist||-||-||-||-|
|SYN-117||Roche/Synosia Therapeutics||Dopamine beta-hydroxylase inhibitor||-||-||-||-|
|598809||GlaxoSmithKline||Dopamine D3 antagonist||-||-||-||-|
|618334||GlaxoSmithKline||Dopamine D3 antagonist||-||-||-||-|
|AIKO-150||AIKO Biotechnology||Opioid antagonist||-||-||-||-|
|NanoBUP||Nanotherapeutics||Opioid agonist & opioid antagonist||-||-||-||-|
|ALKS 33||Alkermes||Narcotic analgesic||-||-||-||-|