Catalysts ahead for the smaller players

Evaluate Vantage has already delved into the key first-quarter clinical data for big pharma and large biotech groups. Now it is the turn of companies with a market cap under $1bn.  

Calliditas’s Tarpeyo already has an accelerated approval in IgA nephropathy, but it now needs to make its mark with confirmatory data on a harder endpoint as competition looms. Elsewhere, Madrigal’s hit this week turns attention to other Nash players: both Viking and 89Bio have mid-stage data approaching. 

Battle in IgAN 

The IgA nephropathy pipeline is busy, with several late-stage readouts expected next year. Calliditas’s Tarpeyo became the first drug for the disease after an accelerated approval in 2021, and now confirmatory data are due. 

IgA nephropathy is a kidney disorder caused by deposits of immunoglobulin A that eventually lead to protein and blood leaking into the urine; some patients also go on to develop kidney failure. Tarpeyo, an oral formulation of budesonide, gained a green light on the surrogate proteinuria endpoint from part A of the Nefigard study, with a placebo-adjusted 31% reduction at nine months. The upcoming data will be on a harder endpoint, estimated glomerular filtration rate (eGFR), a measure of renal function. 

The results will come from part B of the same Nefigard study. Following the nine-month treatment period in part A there was a three-month follow up, then part B consisting of a 12-month observational period. There were earlier hints of stabilisation of renal function when eGFR was measured after nine months of treatment. 

The closest competitor to Calliditas is Travere with sparsentan, a dual endothelin angiotensin receptor antagonist. The drug’s accelerated filing application, due a decision in February, was based on an active control-adjusted 35-point proteinuria reduction from baseline at nine months. Confirmatory eGFR data are due in the second half. Others with phase 3 data later next year include Chinook and Novartis.  

Nash’s fortunes 

Following Madrigal’s high-profile Nash win this week Viking’s shares rocketed 74%. Like Madrigal's resmetirom, Viking’s VK2809 is an oral thyroid hormone receptor-β agonist. A first look at data from the phase 2b Voyage study in patients with biopsy-confirmed Nash is expected next year. 

Voyage tests four different VK2809 doses against placebo in 337 patients, primarily with stage F2/3 fibrosis. The primary measure is the change in liver fat content from baseline to week 12, measured by MRI-PDFF. Secondary measures, including the proportion of patients achieving Nash resolution and fibrosis improvement at 52 weeks, will not report until late 2023 or early 2024. 

An earlier small study in the related liver disease NAFLD showed encouraging reductions in liver fat content, with up to 60% mean relative reduction. VK2809 also showed a favourable safety and tolerability profile. 

Another company trying to make its mark in Nash is 89Bio with pegozafermin, an FGF21 analogue. The 216-patient phase 2b Enliven study is again in biopsy-confirmed Nash patients with stage F2/3 fibrosis. Three doses of pegozafermin, administered by subcutaneous injection, will be tested against placebo.  

The co-primary endpoints are the proportion of participants with histological resolution of Nash without worsening of fibrosis, and with a one-stage or greater decrease in fibrosis stage with no worsening of Nash at 24 weeks. 

Akero’s efruxifermin, also a subcutaneous FGF21 analogue, reported a hit in phase 2 in September, but the primary endpoint analysis was flattered by the exclusion of the handful of patients who dropped out of the trial. 

Madrigal has set the bar by succeeding on both its co-primary endpoints, Nash resolution and fibrosis, and at both doses studied in phase 3, leaving high expectations for the smaller players to live up to. 

The table below contains a fuller list of upcoming catalysts with consensus forecasts from Evaluate Pharma.