Vertex Provides Updates on Multiple Kidney Programs at the American Society of Nephrology (ASN) Annual Kidney Week Congress

October 28, 2024 – BioManufacturing, Pharmaceutical – annual kidney week, kidneys, vertex Pharmaceuticals

New data on povetacicept 80 mg SC Q4 weeks in IgA nephropathy shows mean UPCR
reduction from baseline of 66% observed at 48 weeks, associated with stable renal
function (eGFR) and 63% achieving clinical remission —

• First proteinuria data on povetacicept in primary membranous nephropathy shows mean
  UPCR reduction from baseline of 62% at 24 weeks –
• Global Phase 3 RAINIER trial of povetacicept in IgA nephropathy now underway –
  – Enrollment and dosing ongoing in Phase 3 portion of the global Phase 2/3 pivotal clinical trial
  of inaxaplin for the treatment of APOL1-mediated kidney disease –

25 October, 2024 – MA, US – Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today provided updates on multiple kidney diseases in its pipeline including IgA nephropathy (IgAN), primary membranous nephropathy (pMN), and APOL1-mediated kidney disease (AMKD). These updates demonstrate the transformative potential of Vertex’s investigational therapies in multiple serious kidney diseases, and include positive new data on povetacicept, a dual inhibitor of the BAFF and APRIL pathways, in IgAN and pMN, presented at the American Society of Nephrology’s (ASN) Kidney Week Congress on October 23-27 in San Diego, California.

“We are very pleased with the broadening of our innovative pipeline in renal medicine which now spans programs in AMKD, IgAN, pMN and polycystic kidney disease,” said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. “The new data in IgAN and pMN we shared at this year’s ASN congress continue to reinforce povetacicept as a potential best-in-class therapy and demonstrate its potential as a pipeline-in-a-product. We also continue to make progress in AMKD and autosomal dominant polycystic kidney disease (ADPKD) where we are advancing the first potential treatments to address the underlying cause of these diseases.”

Povetacicept in IgAN

Vertex presented data on 54 patients with IgAN who received povetacicept 80 mg or 240 mg subcutaneously every 4 weeks (SC Q4W). Treatment with povetacicept 80 mg SC Q4W demonstrated a clinically meaningful decrease in proteinuria, with a mean 66% reduction from baseline in urine protein to creatinine ratio at 48 weeks (UPCR; n=8) associated with stable renal function over 48 weeks as assessed by estimated glomerular filtration rate (eGFR). By 48 weeks, 63% (5 out of 8) of study participants achieved clinical remission, defined as UPCR <0.5 g/g, negative hematuria and stable renal function (<25% reduction in eGFR from baseline).

Treatment with povetacicept 240 mg SC Q4W was associated with similar improvements in proteinuria along with stable renal function.

Both doses have been well tolerated in patients with IgAN. The majority of adverse events (AEs) were mild or moderate in severity, and there were no serious adverse events (SAEs) related to povetacicept.

has now initiated RAINIER, a global Phase 3 clinical trial of povetacicept 80 mg in IgAN. A poster presentation #FR-PO854 entitled “Results from Longer Follow-Up with Povetacicept, an Enhanced Dual BAFF/APRIL Antagonist, in IgA Nephropathy (RUBY-3 Study)” was presented during the poster session on October 25 from 10:00 a.m. to 12:00 p.m. PDT.

Povetacicept in pMN

Vertex also presented emerging data in patients with pMN who received povetacicept 80 mg SC Q4W, with three patients having completed at least 24 weeks of treatment. Treatment with povetacicept demonstrated a mean 62% reduction from baseline in UPCR at 24 weeks, associated with stable renal function. By week 24, 67% (2 out of 3) study participants had achieved partial clinical remission, defined as UPCR <3.5 g/g and >50% reduction in UPCR from baseline. Anti-PLA2R1 autoantibodies, which are a marker of disease activity and associated with clinical outcomes, decreased from baseline by a mean of 87% at week 20.

Povetacicept was well tolerated in patients with pMN, with AEs that were mild or moderate in severity. There were no SAEs related to povetacicept. A poster presentation #TH-PO589 entitled “Updated Results with Povetacicept, an Enhanced Dual BAFF/APRIL Antagonist, in Primary Membranous Nephropathy (RUBY-3 Study)” was presented during the poster session on October 24 from 10:00 a.m. to 12:00 p.m. PDT.

AMKD

• Vertex is developing inaxaplin, a potential first-in-class, investigational, oral small molecule inhibitor of APOL1, with the goal of targeting the underlying cause of AMKD. Enrollment and dosing are ongoing in the Phase 3 portion of the global Phase 2/3 pivotal AMPLITUDE clinical trial of inaxaplin. Vertex has the following AMKD poster presentations at ASN:
• Poster presentation #TH-P01203 entitled “AMPLITUDE: A Phase 2/3 Adaptive Trial of Inaxaplin in APOL1-mediated Kidney Disease” was presented during the poster session on October 24 from 10:00 a.m. to 12:00 p.m. PDT.
• Poster presentation #SA-PO701 entitled “Small Molecule APOL1 Channel Inhibitor Reduces Proteinuria, Rescues Podocyte Injury, and Reverses eGFR Decline in an APOL1-Mediated Kidney Disease Mouse Model” will be presented during the poster session on October 26 from 10:00 a.m. to 12:00 p.m. PDT.
• Poster presentation #SA-PO700 entitled “Small Molecule Inhibition of APOL1 Channel Activity Protects Podocytes from Mitochondrial Dysfunction, Cell Death and Barrier Disruption Induced by APOL1 Risk Variants” will be presented during the poster session on October 26 from 10:00 a.m. to 12:00 p.m. PDT. All accepted abstracts are available online on the ASN website.

About Vertex: Vertex is a global biotechnology company that invests in scientific innovation to create
medicines for people with serious diseases. The company has approved medicines that treat the underlying causes of multiple chronic, life-shortening genetic diseases — cystic fibrosis, sickle cell disease and transfusion-dependent beta thalassemia — and continues to advance clinical and research programs in these diseases. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including acute and neuropathic pain, APOL1-mediated kidney disease, IgA nephropathy, primary membranous nephropathy, autosomal dominant polycystic kidney disease, type 1 diabetes and myotonic dystrophy type 1.