Vera Therapeutics’ stock crashed following the reveal of data from a Phase IIb study of atacicept in IgAN.
Vera CEO and founder Marshall Fordyce, M.D./courtesy of Vera Therapeutics
California-based Vera Therapeutics unveiled results Tuesday from the Phase IIb ORIGIN trial showing its immunoglobulin A nephropathy (IgAN) candidate atacicept met the primary endpoint of reduced proteinuria.
At 24 weeks, atacicept reduced urine protein creatinine ratio (UPCR) by 31% relative to baseline values, while placebo comparators saw only a 7% decline. This translated to a statistically significant treatment effect with a p-value of 0.037. At the higher 150-mg dose, atacicept decreased UPCR by 33%.
But are the results good enough to compete in this competitive space?
Following the data drop, Vera stocks fell 65% in after-hours trading Tuesday. Investors may have expected better efficacy numbers from atacicept, which would have put the candidate on more equal footing with its top competitors.
In November, Ionis revealed Phase II data for its own IgAN hopeful IONIS-FB-LRx, which cut 24-hour urinary protein levels by an average of 44% over 29 weeks of treatment. Ionis is advancing this candidate in partnership with Roche.
Also in November, Chinook Therapeutics posted positive Phase I/II results for BION-1301, a potentially disease-modifying monoclonal antibody for IgAN. When given intravenously, Chinook’s candidate reduced proteinuria by up to 66.9% at 52 weeks post-treatment, while subcutaneous dosing led to a 53.8% reduction in nine patients at 24 weeks.
Both Chinook and Ionis/Roche will take their respective investigational IgAN drugs into Phase III this year.
Fordyce: Difficult to Make Comparisons
In an investor call Wednesday, Vera CEO and founder Marshall Fordyce, M.D., nevertheless insisted that atacicept’s performance is competitive.
Calliditas Therapeutics’ Tarpeyo (budesonide), the only drug approved for IgAN, demonstrates a 31% treatment benefit relative to placebo at 36 weeks. Meanwhile, the 150 mg dose of atacicept elicits a 28% treatment benefit at 24 weeks. Sparsentan and sibeprenlibam, both also IgAN therapeutics in development, do not have reported efficacy numbers at 24 weeks. Atacicept’s 36-week proteinuria data remain to be seen.
Fordyce said it is difficult to make reliable comparisons across different trials for different candidates.
ORIGIN is a randomized, double-blinded and placebo-controlled trial enrolling more than 115 IgAN patients who continue to experience proteinuria and are at a high risk of disease progression despite consistent medication.
Atacicept was given at 25-mg, 75-mg or 150-mg doses for 36 weeks of blinded treatment, after which patients will be offered open-label treatment with 150-mg atacicept for 60 more weeks.
Aside from its primary endpoint, the study evaluated the impact of atacicept on exploratory efficacy metrics such as kidney function and serum levels of disease biomarkers.
Throughout 24 weeks of treatment, Vera noted no worrying change in estimated glomerular filtration rate. During this same time, treatment with the candidate significantly reduced serum levels of galactose-deficient IgA1, a key disease activity biomarker.
Atacicept was generally well-tolerated, and the safety profile was consistent with what had previously been reported. Serious treatment-emergent adverse events arose in 2% of atacicept-treated patients, while the discontinuation rate was 2%.
With these data in hand, Vera plans to initiate a pivotal Phase III study of 150 mg atacicept in the first half of this year, pending discussions with the FDA
