Catalysts ahead for the smaller players

Calliditas heads for confirmatory data in IgA nephropathy, while Viking and 89Bio are set for key readouts in Nash.

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

Small companies' Q1 clinical catalysts
Project   Company  Therapy area Catalyst 2028e indication sales ($m) Note/ Vantage coverage
Imetelstat Geron Low or intermediate-1 risk myelodysplastic syndrome (relapsed/ refractory to ESA) Ph3 Imerge early Jan 587

Bristol/Merck's Reblozyl is approved in ring sideroblast + patients (~25% of post-ESA market), imetelstat is being development in both + and - patients (Baird)

ORMD-0801 Oramed Type 2 diabetes Ph3, expected Jan 548 Oral insulin, BLA planned 2024
Bioxcel Acute treatment of agitation in patients with Alzheimer's disease Ph3 Tranquility II H1 525* Approved in agitation in schizophrenia and bipolar disorders I and II (second ph3 planned, Tranquility III)
VK2809 Viking Nash Ph2b Voyage, 12wk MRI-PDFF H1 512 See text
SEL-212 Sobi/ Selecta Gout Ph3 Dissolve I & II 365 Failed a H2H against Krystexxa (Gout flop leaves Sobi red-faced); Sobi paid $100m up front to Selecta
Libtayo +/- RP1 Replimune Cutaneous squamous cell carcinoma Ph2 Cerpass topline H1 344 Registration-directed randomised study (Replimune’s melanoma success looks more than skin deep)
Tarpeyo / Nefecon Calliditas IgA nephropathy (IgAN) Confirmatory ph3 Nefigard part B H1 320 See text
Pliant Idiopathic pulmonary fibrosis Ph2a Integris-IPS 320mg cohort - Earlier data showed an improvement at 80mg dose, but not the higher 160mg (Positive IPF result breathes life into Pliant stock)
Rosnilimab Anaptysbio Moderate-to-severe alopecia Ph2 Azure - Anti-PD-1 MAb
Rezpegaldesleukin (NKTR-358, LY3471851) Nektar/ Lilly SLE Ph2 Island-SLE, PC Nov 2022 - IL-2 project, Lilly dropped the asset in UC, important for Nektar given the failure of bempegaldesleukin (Abbvie takes its Treg cue)
Pemvidutide Altimmune Obesity Ph2 Momentum, changes in body weight after 24 weeks, interim from ~160 subjects - GLP-1/glucagon dual receptor agonist, disappointed in NAFLD (Altimmune posts a metabolic let-down)
(bempedoic acid)
Esperion Cardiovascular disease Ph3 Clear Outcomes (CV outcomes trial) full data possibly at ACC meeting in March - Needed for CV claim, toplined positive in December; Nexletol is positioned between statins and PCSK9s
Atacicept Vera IgA nephropathy (IgAN) Ph2b topline Origin - Primary endpoint proteinuria data at 24 weeks, plans to start pivotal ph3 in 2023 (busy pipeline of IgAN projects, see text) 
Pegozafermin (BIO89-100) 89Bio Nash Ph2b Enliven - See text
*Forecasts under agitation. PC: primary completion. Source: Evaluate Pharma &

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