These were perhaps not the Nash data the sector was looking for, but they provided some respite at a time when Covid-19 is derailing normal business activities. Akero, a company that has been on the public markets for less than a year, reported stellar results in the first cut of a mid-stage Nash trial of its pipeline lead, AKR-001.
The group climbed 23% yesterday to close 33% above the price of its $92m Nasdaq IPO last June. Its success will clearly be of interest to other developers of assets that use AKR-001’s FGF21 stimulant mechanism, including Ambrx, 89bio and Novo Nordisk, but there is still scope for Covid-19 to disrupt Akero’s party.
This is because yesterday’s results related only to MRI data, including the primary endpoint, 12-week change in liver fat fraction versus placebo. A comparison of biopsies, from treated and control subjects, is a more robust measure, but when these data might be available seems to be up in the air.
Akero said 50 subjects, amounting to 45% of the Balanced study’s population, were eligible for biopsies, but as of two days ago only half of these had been collected. Paired biopsy data are expected in the current quarter, but how much Covid-19 will interfere with biopsy collection and patient follow-up is “unclear”, Akero said.
The most keenly awaited Nash dataset remains the interim result of Genfit’s Resolve-It trial of elafibranor, which after several delays is still due in the current quarter. The US adcom to review Intercept’s Ocaliva, meanwhile, has been delayed until June 9 amid the coronavirus pandemic.
Nevertheless, the non-invasive MRI data Akero released yesterday do look impressive. Relative reductions in liver fat were 63% to 72% versus baseline for the three AKR-001 doses tested, with a numerical dose response; all three hit statistical significance versus placebo recipients, who showed a 0% reduction.
Evercore ISI analysts wrote that this comfortably exceeded expectations of a 50% MRI reduction. They also pointed to competitor benchmark biopsy data that Akero could now shoot for, with some having shown 25% Nash resolution and 40% one-stage fibrosis improvement, though of course performance of the placebo cohort has to be netted off.
The MRI data alone position AKR-001 as a potential best-in-class asset, Evercore said. Other FGF21 stimulant projects in development include Bristol-Myers Squibb/Ambrx’s pegbelfermin and 89bio’s BIO89-100, which could yield mid-stage Nash data this year, the Covid-19 pandemic permitting.
|Clinical-stage fibroblast growth factors for Nash|
|AKR-001||Akero (ex Amgen)||FGF21 stimulant||Once weekly||NCT03976401 biopsy data in Q2|
|NGM282/aldafermin||NGM||FGF19 regulator||Once daily||NCT02443116 cohort 4 yielded biopsy data in Feb 2020; NCT03912532 in 2020|
|Pegbelfermin/BMS-986036||Bristol-Myers Squibb/Ambrx||FGF21 stimulant||Once daily/once weekly||NCT03486899 in H1, NCT03486912 in H2 2020|
|BIO89-100||89bio||FGF21 stimulant||Once weekly/every two weeks||NCT04048135 in 2020|
|MK-3655/NGM313||Merck & Co/NGM||FGFR1c antibody||Once monthly||Two phase I studies completed|
|NN9500||Novo Nordisk||FGF21 stimulant||Not disclosed||In phase I, according to company|
|Sources: EvaluatePharma & clinicaltrials.gov.|
Another important rival is NGM Biopharmaceuticals’ aldafermin, which is an FGF19 regulator that last year showed a relative fat content reduction of up to 60% in phase II. However, this came at the cost of a significant jump in patients’ LDL, a side-effect that will have to be watched, but which Akero says AKR-001 does not share.
Nevertheless, NGM in February generated biopsy data showing 22% of aldafermin-treated subjects showing fibrosis improvement and Nash resolution, versus 0% for placebo, from a cohort that had shown fat reduction by MRI of 40%. Thus the opportunity for Akero, with much better MRI reductions, is to crush the opposition with biopsy data – if Covid-19 does not scupper the study, of course.
Like Akero, NGM and 89bio floated last year. If Akero proves to be the pick of the bunch Amgen might come to rue the day it sold AKR-001 to it for a mere $5m.