Intercept is building up to present full data from the Regenerate trial of Ocaliva in Nash on Thursday afternoon, and the abstract unveiled just now does not seem to contain any nasty surprises. Safety data look in line with topline results released earlier this year, while a couple of secondary endpoints detailed suggest other signals of efficacy, though only for the high 25mg Ocaliva dose.
Regenerate was already known to have hit on only one of its co-primary endpoints – improvement in fibrosis – and only at 25mg. The co-primary Nash resolution endpoint was decisively missed. Newly released secondary endpoints include a finding that 35% of patients receiving the 25mg dose showed improvements in hepatocellular ballooning and 44% had improvements in lobular inflammation. Both are disease markers that physicians will be encouraged to see heading in reverse.
On safety, the abstract outlines numbers that had already been released in February, though the full presentation of the data in Vienna will be scrutinised closely, especially when it comes to full data on liver toxicity .
A rise in LDL cholesterol and liver toxicity are the big concerns, while a 51% rate of pruritus at the 25mg dose is a talking point as to whether a therapeutic window exists for Ocaliva. Such issues have become particularly relevant as Intercept stock has regained the losses it sustained when Regenerate was toplined in February.
|Intercept’s EASL presentation of Regenerate|
|Placebo||Ocaliva 10mg||Ocaliva 25mg|
|Stage 2 & 3 fibrosis patients||n = 311||n = 312||n = 308|
|Fibrosis improvement + no worsening of Nash||11.9%||17.6% (p=0.0446)||23.1% (p=0.0002)|
|Nash resolution + no worsening of fibrosis||8.0%||11.2% (p=0.1814)||11.7% (p=0.1268)|
|Improvement in hepatocellular ballooning*||23.2%||27.2% (p=0.2423)||35.1% (p=0.0011)|
|Improvement in lobular inflammation*||35.7%||39.1% (p=0.3380)||44.2% (p=0.0322)|
|Hepatic disorder SAEs**||<1%||<1%||<1%|
|Overall study discontinuations||16%||17%||15%|
|*New data; **most common in 25mg group. Source: EASL abstract.|
EvaluatePharma’s sellside consensus has sales of Ocaliva reaching $2bn by 2024, though the real commercial potential is still very much an open question. As well as toxicity concerns that will prompt regulators to look very hard at the more effective higher dose, there is much debate around the ultimate target population.
Restricting the drug to those with advanced fibrosis or implementing a requirement of biopsy-diagnosed Nash, for example, are big swing factors. Still, the need for pharmacological options in a disease that is growing in prevalence is likely to be frequently cited in Vienna over the next few days.
“These data are very exciting as they demonstrate for the first time in a phase III trial that medical therapy, in this case obeticholic acid, is able to improve liver fibrosis compared to placebo – a key treatment goal in Nash,” Professor Philip Newsome, vice-secretary of EASL, was quoted as saying in a conference press release.
Full data will be presented at 3:30pm on April 11, and all eyes will be on the details.
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