Easl 2023 – Biomarkers back a new Nash player

Boston’s Novartis cast-off looks highly promising versus better-known projects.

Hard Nash endpoint results with 89Bio’s pegozafermin, released at the Easl meeting today, do not add much to what was toplined in March. A new cut of biomarker data are more interesting – not for what they show about 89Bio’s project, but for the light they shed on a mechanistically similar candidate from a private group: Boston Pharmaceuticals. 

On a cross-trial basis Boston’s BOS-580 looks as effective at cutting markers of liver fat and liver damage than two better-known mid-stage rivals, pegozafermin and Akero’s efruxifermin. Since these latter compounds have been shown to improve Nash and fibrosis, expectations for Boston’s molecule must now be very high. 

All three of these agents are subcutaneously administered analogues of fibroblast growth factor 21 (FGF21), an endogenous hormone that modulates drivers of lipid metabolism and Nash including triglyceride reduction, glycaemic control, steatosis, inflammation and fibrosis. 

On Nash and liver fibrosis endpoints, 89Bio's pegozafermin looks better than Akero's efruxiermin when the data from their separate phase 2 trials are compared. Naturally this is only a rough guide – all the more so since Akero used a per-protocol rather than a more rigorous intent-to-treat analysis in its study, Harmony.

Boston has not yet reported Nash or fibrosis data on its FGF21, BOS-580, so all industry watchers have to go on so far is its effects on biomarkers, including liver fat fraction and levels of ALT, a marker of hepatic damage. These are exploratory endpoints from a trial focused on safety. 

Note: Data at 24wk for Akero and 89Bio, from the Harmony and Enliven trials, respectively. Data at 12wk, from unnamed Ph2a trial for Boston. Graph shows only the highest two doses in each trial. See Easl abstracts LBO-05 and LBP-22.

And here Boston looks very competitive with the other two, according to data presented as a poster at the Easl meeting on Wednesday. It should be noted that the data for Boston are at three months, whereas the data for Akero and 89Bio are at six months. Since responses might be expected to deepen over time, this suggests BOS-580 is all the more effective. 

Another aspect is dosing frequency. Efruxifermin is given weekly, and 89Bio is pursuing both weekly and fortnightly dosing with pegozafermin. Boston, however, dosed BOS-580 every two weeks and once a month in its study. 

Faster or better?

Of course, this might not translate into actual benefits for Nash patients. The clinicaltrials.gov listing for Boston’s phase 2 trial makes no mention of hard endpoints such as the two established metrics for disease improvement, resolution of Nash without worsening of fibrosis and fibrosis improvement without worsening of Nash. Both efruxifermin and pegozafermin have succeeded here. 

The company declined to answer Evaluate Vantage's questions regarding whether, or when, it might investigate BOS-580’s effects on these more convincing endpoints. But it seems likely that Boston will need to conduct another phase 2 trial, and that will put it behind the other two players, both of which are finalising phase 3 plans. 

Whether Boston will ultimately come out the winner is a question for another day. What is clear is that Novartis seems to have dropped the ball. The big pharma licensed BOS-580 to Boston in 2020, instead choosing to concentrate on a different Nash project, the FXR agonist tropifexor. Tropifexor no longer appears in Novartis’s pipeline.

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