It was always going to be a hard ask and today Agennix’s talactoferrin joined a long list of drugs that have tried and failed to crack sepsis. The disorder has proved too tough for numerous agents including those of Eli Lily’s IC14 and Takeda’s TAK-242 and still remains one of the most elusive disease targets in the industry.
The clinical halt of one of the most advanced drugs in development by a safety monitoring board now leaves only two drugs in later stage development (see table); the only approved drug, Xigris, was withdrawn last year after its effectiveness could not be confirmed.
Of the remaining drugs in development the difficult task of making any impact on survival rates has been passed to BTG and AstraZeneca’s CytoFab or AZD9773, currently in phase II. The drug, an antibody, is the most promising and also the only one that is currently generating sales forecasts, albeit a very modest $6m by 2016.
|Late stage sepsis pipeline|
|Product||Company||Pharmacological Class||Clinical Trial IDs|
|Phase II||AZD9773/CytoFab||BTG/AstraZeneca||Anti-tumour necrosis factor alpha (TNFa) polyclonal MAb||NCT01145560|
|FE202158||Ferring Pharmaceuticals||V1a receptor agonist||NCT01000649|
But the trick for most sepsis drugs appears to be translating good phase II results into a win in phase III. Eisai last year saw its candidate eritoran (E5564) implode during phase III trials and today’s results from talactoferrin underscore just how hard it is to cross that line (Eritoran failure overshadows eventful few days for Eisai, January 25, 2011).
Equally telling is the small number of drugs that are in development for the illness, indicating that many companies have decided that the difficulty of trying to go after this incredibly hard indication outweigh the rewards.
In the last 10 years a total of 14 drugs have been abandoned in development, including five in phase III and another five in phase II.
|Abandoned sepsis projects over the last 10 years|
However, given the lack of available treatment, pretty much any drug that does show a benefit in the disorder and is reasonably well tolerated would be a dead cert blockbuster; both talactoferrin and eritoran had analysts pencilling in peak sales of over $1.1bn.
AZD9773 is due to report results by the middle of the year and the outcome will be closely watched. Ferring Pharmaceuticals' phase II drug completed trials in October, but the company has said little on its development plans.
Not quite the end?
As for the fate of talactoferrin, the market was swift to react to news that a safety monitoring board had halted the phase II/III 350-patient Oasis trial (NCT01273779), following more deaths in the drug arm than placebo. Shares in the Heidelburg-based group were 28% lower at €1.92 in early afternoon trading, a new low.
The investor nursing the biggest hit will be Dietmar Hopp, the serial investor who thanks to a conversion of loans into equity in December is now Agennix’s biggest shareholder with a 65% stake.
What Agennix does now in sepsis is unclear and the group will be eager to unblind the data to see where the promising results seen in previous smaller phase II trials diverged from today’s announcement.
The drug had previously shown an impressive 12.5% reduction in 28-day all-cause mortality compared to placebo. Xigris was improved on a 6% reduction, although this result could not be repeated in later trials.
The failure in sepsis might not mark the end of talactoferrin, a drug derived from human breast milk. The compound is also being studied in third-line phase III non-small cell lung cancer and is due to report in the first half of this year.
But some are bound to see the results in sepsis as a read across to any success in NSCLC as the group itself has argued that the effectiveness of talactoferrin in two widely divergent disorders is because it is primarily an immunotherapy (EP Vantage Interview - Agennix hoping for success with multitasking talactoferrin, July 07, 2011). Having failed in sepsis it could now fail in NSCLC.
But whatever the fate of talactoferrin yet another hope in finding a well tolerated, and effective treatment for sepsis appears to have slipped away. Given the paucity of the remaining pipeline any more failures will crush already small hopes.