As the opioid epidemic ratchets up in the US, the pressure is on to find new options for pain management. While many have found it difficult to succeed in this area, Innocoll has taken a big step in the right direction with positive results from two phase III trials of its bupivacaine-collagen sponge Xaracoll.
The company’s share price yesterday shot up 48% on the news, but this might be a case of overexcitement. Approval of the product looks likely, but market uptake could be hampered by its less than desirable delivery route, via a surgical implant, and unconvincing long-term data.
At present, Xaracoll does not make EvaluatePharma’s forecast top five postoperative pain drugs in 2022, which does feature unapproved assets like Cara Therapeutics’ CR845 and Trevena’s TRV130, both in phase III, and Heron Therapeutics’ HTX-011, in phase II (Upcoming events – Cara, Heron and Seres get ready for next phase, April 22, 2016).
Still, these more conventional injectable drugs still have it all to do – at least Xaracoll already has phase III data under its belt.
Glitch in the Matrix?
The studies, Matrix-1 and Matrix-2, both met their primary endpoints, showing a significant decrease in the sum of pain intensity over 24 hours (SPI24) compared with placebo in patients who had undergone open abdominal hernia repair.
Innocoll claims that these represent the first positive phase III results for a long-acting, opioid-sparing local anaesthetic in hernia.
Longer-term data were not as impressive. Only one trial met the secondary endpoint of SPI48, although pooled data from both studies showed a p value of 0.003. And neither study achieved significance on the SPI72 endpoint, although again the pooled data came in under p=0.05.
|Sum of pain intensity over 24 hours (primary endpoint)||p=0.0004||p<0.0001|
|Sum of pain intensity over 48 hours (secondary endpoint)||p=0.057||p=0.027|
The company said there had also been a significant reduction in opioid consumption and an increase in the time to the first use of opioids, but would not give more details, saying it would present or publish full data in the future.
Innocoll plans to file the product with the FDA this year. Its chief executive, Tony Zook, said during a conference call the agency was expecting to see pooled data, “so submitting that would be normal”.
However, “it is unclear how the FDA will interpret this data and whether Xaracoll will be granted a long-duration claim”, wrote Leerink analysts.
If approved, the bioresorbable implant will go up against the top postoperative pain drug, Pacira’s Exparel, which is given by an arguably more convenient injection and has a label claim for 72 hours of pain relief.
And Heron’s HTX-011, a reformulation of bupivacaine and meloxicam, has shown impressive results for up to 72 hours, albeit in phase II and in a different setting, post-bunionectomy (Heron soars with phase II pain success, September 23, 2015).
But long-acting opioid-sparing analgesics are only currently used in around 5% of eligible surgeries in the US, Innocoll executives noted during the call. The company hopes to grow the market rather than just taking share from existing products like Exparel.
With opioid addiction so high on the agenda in the US, market expansion looks likely. The question is whether Innocoll will be able to make the most of this.