Event - Titan awaiting confirmation for addiction treatment

The long-acting opioid addiction treatment probuphine is due to report pivotal data by the end of the month, and the fate of developer Titan Pharmaceuticals hangs in the balance. With less than $1m cash, enough to last only another nine months, it goes without saying a failure would leave the California group with few options.

Given that the product is a reformulation of the opioid agonist buprenorphine, already used in addiction therapy as one-half of Reckitt Benckiser’s Suboxone, there is reason to hope that the Titan candidate will be successful in helping opioid abusers kick the habit. By offering a product that gives patients six months of low but steady therapeutic dose, Titan aims to reduce cravings and improve compliance in this hard-to-treat population.

Product Probuphine
Company Titan Pharmaceuticals
Market cap $118m
Product NPV n/a
% of market cap n/a
Event type Phase III results
Indication Opioid addiction
Date Q2 2011
Trial ID NCT01114308  

Seeking confirmation

The phase III trial against placebo and Suboxone aims to confirm the findings of an earlier trial against placebo alone, which reported data nearly three years ago. That trial reduced illicit drug use as measured by urine testing performed three times a week.

The current trial adds a non-inferiority arm against Suboxone, a sublingual formulation of buprenorphine, which had sales of $1.04bn in 2010, but is expected to face generic competition starting this year. The hope is that probuphine, an upper-arm implant that slowly secretes buprenorphine, will eliminate morning withdrawal symptoms, variable blood levels and misuse that can result from suboptimal dosage.

Partially funded by a $7.6m grant from the National Institute on Drug Abuse, the new trial enrolled 100 in both active drug arms and 50 in its placebo arm, again using urine testing as a primary endpoint.

Success in the trial will probably trigger partnership talks as Titan, with a market capitalisation of $118m, is not in a position to go to market itself. Such a licensing deal would come in handy. Although the company received $2.5m in royalties for pain drug Fanapt in 2010, its finances were insufficient to avoid a restructuring of debt this year, and the company relied on US government economic stimulus cash to finance part of the R&D for probuphine.

Success also would help to validate Titan’s long-acting technology and thus help build some confidence in the firm, which in 2008 de-listed from the AMEX at about the same time as it slashed its workforce by more than 40%. According to EvaluatePharma data the company is testing long-acting versions of Fanapt and a long-acting dopamine agonist to treat Parkinson’s disease using the company’s ProNeura delivery technology.

Development strategies

Few analysts cover the company, making estimates of probuphine’s potential hard to come by. Branded opioid addiction treatments are forecast to sell $1.14bn in 2016, led by Suboxone but also assisted by Alkermes’ Vivitrol, which entered the market last year (Therapeutic focus – Drug developers fail to get the habit with opioid addiction, November 30, 2009).

Although there are an estimated 750,000 people worldwide receiving treatments for opioid addiction, the space also has significant generic presence with naltrexone and methadone having been off patent for years. Like probuphine, Vivitrol also gains intellectual property protection by being a long-acting variant of the generic naltrexone, which is also used in alcohol dependency.

EvaluatePharma’s pipeline data for the space reveals limited novel late-stage development, with only probuphine in phase III for non-acute treatment of addiction, and three of the seven products – two of them buprenorphine - in phase II seeking approval using proprietary drug delivery technology (see table below).

Orexo’s OX219, a buprenorphine based product, and ALKS33 are the only clinical-stage products with sales estimates attached - Ketas records sales in asthma and other indications, primarily in Japan - suggesting that analysts have yet to see much potential in developing products for this market.

Thus while positive findings for probuphine are likely to revive hopes for Titan, it may take more pipeline progress before observers are willing to get excited about the opioid treatment market again.

Opioid addiction treatment pipeline
Annual sales ww ($m)
2010 2011 2012 2013 2014 2015 2016
Phase III Probuphine Titan Pharmaceuticals NDA + Proprietary Drug Delivery - - - - - - -
Phase II OX219 Orexo NDA + Proprietary Drug Delivery - - 81 90 61 55 48
AV411 MediciNova NME (Patented Compound) - - - - - - -
CAM2038 Camurus NDA + Proprietary Drug Delivery - - - - - - -
PPAR agonist Omeros NME (Patented Compound) - - - - - - -
MN-166 MediciNova NME (Patented Compound) - - - - - - -
Lobeline Yaupon Therapeutics NDA (Non-proprietary Drug Delivery) - - - - - - -
Ketas Kyorin Holdings NME (Patented Compound) 47 45 39 36 31 26 21
Phase I NanoBUP Nanotherapeutics NDA + Proprietary Drug Delivery - - - - - - -
GSK618334 GlaxoSmithKline NME (Patented Compound) - - - - - - -
AIKO-150 AIKO Biotechnology New Derivative - - - - - - -
BEMA Bupreonorphine/Naloxone BioDelivery Sciences International NDA + Proprietary Drug Delivery - - - - - - -
GSK598809 GlaxoSmithKline NME (Patented Compound) - - - - - - -
SYN-115 Biotie Therapies + UCB NME (Patented Compound) - - - - - - -
ALKS 33 Alkermes NME (Patented Compound) - - - - 1 7 17

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