Welcome to your weekly roundup of approaching clinical readouts. Aurinia Pharmaceuticals should soon know whether its sole pipeline project, the calcineurin inhibitor voclosporin, has a future in lupus nephritis.
The company is due to report data from its phase III Aurora trial towards the end of the year, and the onus will be on safety, given an imbalance of deaths seen in phase II. The 258-patient pivotal Aurora study compares voclosporin plus standard of care versus standard of care alone; the primary endpoint is the number of patients achieving a renal response at one year.
A 20% or greater difference versus control would represent a home run on efficacy, say Leerink analysts. However, even a difference of 10-20% could be enough to justify approval – provided that safety is clean.
This is not a given after 12 deaths among voclosporin-treated patients in the phase II Aura-LV trial, versus just one in the control group. All were deemed unrelated to treatment, but nevertheless spooked investors.
Most of the fatalities in phase II occurred at hospitals in Sri Lanka and Bangladesh, where patients had poor access to basic healthcare, and apparently these sites recruited a disproportionate number of active cohort subjects. Aurinia has avoided these regions when recruiting for Aurora.
Still, the omens for efficacy are not all positive either: in phase II only the lower dose of voclosporin, 23.7mg twice daily, met the primary endpoint, remission at 24 weeks.
Voclosporin is forecast to bring in $648m by 2024, according to EvaluatePharma sellside consensus, with all but $6m of this set to come in lupus. Getting a result in Aurora could therefore revive Aurinia's fortunes and give it a shot at a market with few available therapies.
However, the space could be about to get more crowded, with a recent phase III win for Astrazeneca’s anifrolumab, as well as mid-stage success for Roche’s Gazyva, which led to the latter receiving breakthrough therapy designation from the US FDA this week.
Traditionally BTK inhibitors have been used in oncology rather than automimmune diseases but Principia Bio is looking to target the latter with PRN1008. Phase II data are due in the fourth quarter from two trials, one in pemphigus vulgaris and the other immune thrombocytopenic purpura (ITP).
The rationale behind using BTK inhibitors in autoimmune diseases is that they deplete B cells, which are implicated in these disorders. However, older BTK inhibitors are linked with bleeding, which has made them unsuitable for chronic dosing. Principia believes it has created a safer candidate in PRN1008.
In ITP, a platelet disorder, four doses of PRN1008 are being tested in a single-arm study in patients with relapsed primary or secondary disease.
Patients had platelet counts of <30,000/µl at baseline; the primary efficacy measure is the proportion of patients achieving two or more consecutive counts of ≥50,000/µl and an increase of ≥20,000/µl at 24 weeks.
Stifel analysts believe a 30% or greater response would be considered a strong signal. In July Principia added a long-term extension cohort for responders, sparking hopes that efficacy had been seen.
Meanwhile, Principia will report more data in pemphigus vulgaris, which involves severe blistering of the skin and mucous membranes, from its single-arm phase II Believe-PV study.
The trial has already yielded results in 24 patients, showing a 17% complete response rate after 12 weeks of therapy, rising to 25% after a 12-week post-treatment follow-up period.
In the fourth quarter, data will be available from 10-15 new patients in an extension arm testing 24 weeks’ treatment and a four-week follow-up. Longer treatment could lead to a deepening response rate. Principia has already started the phase III Pegasus trial testing 36 weeks of treatment.
Roche’s Rituxan, an anti-CD20 Mab that also targets B cells, was approved last year to treat newly diagnosed pemphigus vulgaris patients. Stifel analysts believe PRN1008 will be used as a maintenance treatment in the 20-25% of patients who don’t respond to Rituxan.
PRN1008 is Principia’s lead asset and 2024 sales are forecast to reach $226m according to EvaluatePharma consensus.
|PRN1008's upcoming readouts|
|Indication||2024e indication sales ($m)||Trial name/ID||Details|
|Immune thrombocytopenic purpura||45||NCT03395210||24 weeks’ treatment, 4 weeks’ follow-up. Doses: 200mg, 400mg (both once a day) and 300mg, 400mg (both twice a day). Up-titration allowed. Data Q4.|
|Pemphigus vulgaris||181||Believe-PV, NCT02704429||Part A: 12 weeks’ treatment, 12 weeks’ follow-up (reported); Part B: 24 weeks’ treatment, 4 weeks’ follow-up, data due Q4|
|Pegasus, NCT03762265||36 weeks treatment, likely due 2022 (primary: complete remission)|
|Source: EvaluatePharma, clinicaltrials.gov.|