The pharmaceutical industry has long turned to sustained-release formulations to protect fading franchises, and the opioid dependence market is the latest to attempt the move. An implanted product won approval in May, and two once-monthly injectables are approaching the US regulator, while the market for orals is increasingly turning generic.
Many expect these long-acting products to succeed commercially, not least because of a substantial political tailwind – opioid addiction remains a huge health concern in the US. Proponents also point to the success of the injected antipsychotics, which have generated respectable demand despite the presence of cheaper generics. As is frequently the case these days, however, price will be the biggest obstacle, and companies will have to fight hard for a premium (see table below).
Heavy hints have been dropped that these new long-acting opioid antagonists will be launched at a similar price to once-monthly injected schizophrenia therapies. Invega Sustenna, Johnson & Johnson’s once-monthly shot, was sold last year to US government buyers for $1,265-1,772 per unit, while Otsuka’s Abilify Maintena came in at $1,000-1,400, according to EvaluatePharma.
This would represent a substantial premium to Suboxone, the leading anti-addiction medication from Indivior which represents about half the market; most of these drugs are versions of buprenorphine. The most popular pack containing 30 doses cost Medicaid $242 in 2015, according to EvaluatePharma, although some patients use more than this in one month.
Health economic arguments will centre on greater compliance and the associated benefits. For example Braeburn Pharmaceuticals, which recently launched the implanted product Probuphine, has presented data showing that patients had a 45% lower chance of relapse and an 80% lower chance of going to rehab than patients taking oral buprenorphine.
Arguments around abuse potential and so-called “divergence” are possibly even more convincing. The illegal market for buprenorphine is a huge problem alongside abuse of opioids themselves. By removing the need to hand the drug over to patients to take home, and with the injectable product itself much less likely to be used outside clinical practice, the products could help lessen a major route to abuse.
As such, many believe that the injected anti-opioids actually have a stronger case for a premium price than injected anti-psychotics, which do not end up on the streets. Add to this the incentive for doctors to use an injection, which they are paid to administer unlike the oral forms, and the foundations for taking share of the market appear to be in place.
|Long-acting anti-addiction therapies – all buprenorphine unless stated|
|Product||Route of admin||Company||Status|
|RBP-6000||Once-monthly injection||Indivior||Phase III|
|Probuphine (implant)||Six monthly implant||Braeburn Pharmaceuticals||Marketed|
|CAM2038||Once-weekly and once monthly injection||Braeburn/Camurus||Phase III|
Those moving into this market with long-acting injectable forms of buprenorphine include Indivior, the dominant player in this space, which last week released compelling data on its phase III candidate, RBP-6000. This could be on the market later next year (Indivior’s addiction to the opioid market is paying dividends, August 17, 2016).
Braeburn is also emerging as a key player. As well as the implant Probuphine, which it licensed from Titan Pharmaceuticals, it has US rights to CAM2038. This was developed by the Swedish drug developer Camurus, which has pushed forward once-weekly and once-monthly projects. Data should emerge from its pivotal programme later this year.
Probuphine, meanwhile, hit the market in May after a rocky regulatory ride. It was knocked back by the FDA in 2013 over concerns about the training required to insert and remove the implant correctly, and questions over efficacy (Titan not so mighty after FDA rejection, May 1, 2013).
Titan reckons this market could be worth $300-500m at peak – as Braeburn is private sellside forecasts are not available. This seems to be an optimistic outlook given that implantable products have not enjoyed success historically, and concerns about divergence still exist – some fear that addicts could dig the implants out of their arms for illicit use by themselves or others.
One other injected product exists – Alkermes’ Vivitrol. This was the first sustained-release product to enter the opioid market back in 2010 – it has been sold for alcohol addiction since 2006. The once-monthly injectable form of naltrexone is labelled to prevent relapse to opioid dependence, following opioid detoxification.
Alkermes reckons that Vivitrol only captures around 1-2% market share in opioid dependence, but sales are projected to grow strongly in the coming years, driven by beneficial legislation and a growing market.
Only last month the Comprehensive Addiction & Recovery Act (CARA) was enacted, allowing nurses and physician assistants to prescribe addiction medication as well as doctors. And the US health department also just moved to raise the cap on the number of patients who can be treated by qualified doctors from 100 to 275.
It is clear that the lawmakers have been convinced that this market is important. For those looking to sell premium-priced products, however, it is the payers that need persuading.
Braeburn has said it would price Probuphine at $4,950 for a six-month course – more than traditional forms of buprenorphine but, it claims, significantly lower than Vivitrol. According to EvaluatePharma’s pricing data, each Vivitrol injection cost Medicaid $1,200 last year.
To appease insurers Braeburn has offered money back if the overall cost of care for a patient taking Probuphine exceeds the cost of treatment for patients taking other forms of buprenorphine. Indivior and Braeburn have not yet discussed whether these sorts of incentives will be offered alongside the injectable agents.
Payers have shown remarkable resistance to arguments in favour of medical need, when cheaper alternatives are available. So executives can speak boldly of favourable legislative environments, but they will still have to unleash vigorous health economic campaigns to get those holding the purse strings on side.
|A decade in the opioid dependence market|
|WW sales by indication ($m)|
|Total market (incl. others)||1,320||1,132||1,233||1,479|
|*Vivitrol sales assume roughly 50/50 split between alcohol and opioid sales. Source: EvaluatePharma.|