Dr. Richard Philipson, CMO at Calliditas Shares Results & Insights from P-III Study Evaluating Tarpeyo

Shots:

Dr. Richard talked about the results from the NefIgArd P-III trial evaluating Tarpeyo (Nefecon) for the treatment of IgA Nephropathy
He also highlighted the safety and efficacy results from the NefIgArd study. He also spoke more about Trapeyo and the roadmap for its global approval and commercialization
The interview shows up how Calliditas is developing novel treatments in orphan indications, in addition to renal and hepatic diseases

Smriti: What is IgA Nephropathy, and how is it different from any other chronic kidney disease?

Richard Philipson: IgAN is a serious, progressive kidney disease, in which up to 50% of patients develop end-stage renal disease (ESRD) within ten to twenty years. Unlike other conditions that cause chronic kidney disease, IgA nephropathy is thought to originate in the distal part of the intestine, specifically in the ileum. Peyer’s patches, which are concentrated within the gut-associated lymphoid tissue in the ileum, have been identified as a major source of mucosal-type IgA antibodies. Patients with IgA nephropathy have elevated levels of mucosal-type IgA in the circulation, which generates an autoimmune response that results in pathogenic immune complexes that deposit in the glomeruli, the kidney’s filtration apparatus leading to kidney damage and loss of kidney function.

Smriti: Tell us a little more about Tarpeyo (MoA, RoA, formulation, and other details).

Richard Philipson: TARPEYO is an oral, delayed-release formulation of budesonide, a corticosteroid with potent glucocorticoid activity and weak mineralocorticoid activity that undergoes substantial first-pass metabolism, resulting in limited systemic exposure. It was designed as a 4 mg delayed-release capsule with an enteric coating so that it remains intact until it reaches the ileum. Each capsule contains beads of budesonide coated with various polymers designed to target the area with the highest concentration of Peyer’s patches, with the intention of having a disease-modifying effect.

Smriti: Tarpeyo is a corticosteroid, can you please tell us more about the safety results from the NefIgArd study?

Richard Philipson: The majority of adverse reactions were mild or moderate in severity. The most frequently reported adverse reactions (≥5% of TARPEYO-treated patients and ≥2% higher than Placebo) were: hypertension, peripheral edema, muscle spasms, acne, dermatitis, weight increase, dyspnea, face edema, dyspepsia, fatigue, hirsutism. Approximately 90% of patients stayed on treatment in both study arms in the Phase 3 trial.

Smriti: We understand that FDA approval is based on NefIgArd part A results, when can we expect the complete results of the study?

Richard Philipson: We are looking forward to the readout of Part B of the NefIgArd trial in the first half of 2023 in order to report the long-term impact of the treatment on patients’ underlying kidney function.

Smriti: NefIgArd part A results were announced last year, would like to discuss some additional newer results/ post-hoc analysis?

Richard Philipson: Results from Part A of the NefIgArd trial were announced in late 2020 and were the basis of TAREPYO’s accelerated approval. Part A met its primary objective of demonstrating a statistically significant and clinically meaningful reduction in proteinuria, after 9 months of treatment with 16 mg once daily of TARPEYO compared to placebo, on top of renin-angiotensin system inhibitor (RASi) therapy. Patients taking TARPEYO plus RASi showed a statistically significant 34% reduction in proteinuria from baseline vs 5% with RASi alone.

We were thrilled to have Part A results published in Kidney International in October 2022. The publication highlights the safety results and efficacy data related to both proteinuria and estimated glomerular filtration rate (eGFR). The publication provides additional clinically relevant analysis over the entire 12-month time period observed in Part A, inclusive of the 3-month follow-up when no drug was administered. We believe these data provide reinforcing evidence of the differentiation that TARPEYO represents, as well as the potential to be disease-modifying.

Smriti: After the complete results are out do you think Tarpeyo will be able to enjoy the first-line treatment spot?

Richard Philipson: While we cannot make assumptions based on what we have seen to date, we are confident in the results and feedback we have received this past year. We will continue to work with the Agency on labeling updates when appropriate and will maintain our strategic sales and marketing efforts to educate nephrologists on TARPEYO as a potential treatment option for their patients with IgA nephropathy.

Smriti: When is the expected launch of Tarpeyo in the EU and other countries like China among others?

Richard Philipson: Calliditas received conditional approval in July from the European Commission under the brand name Kinpeygo®. Our European commercial partner, STADA Arzneimittel AG, has since launched Kinpeygo in Germany with additional European countries to follow. Everest Medicines, our partner in China, received an acceptance by the Chinese regulatory authority of the New Drug Application for Nefecon; a decision regarding a potential approval is expected in the second half of 2023.

Smriti: Do we see that other organizations are assessing their molecules in other CKD indications such as C3G, Lupus Nephritis, PNH, etc?

Richard Philipson: TARPEYO was designed specifically to target what is thought to be the origin of IgA nephropathy. Because of this, we are not evaluating the potential use for TARPEYO in other disease states. We have a robust pipeline that includes setanaxib, the first NOX inhibitor to reach the clinical trial stage; we will expect clinical readouts for that program in 2023.

Source: Canva

About the Author:

Dr. Richard Philipson is the CMO at Calliditas Therapeutics. He is also a physician with 24 years of experience in the pharmaceutical industry from both large pharmaceutical companies and smaller biotechs. He has extensive experience in rare diseases, having brought several products from early development to the market. Before joining the industry, Richard worked as a physician in several clinical positions with various patient populations, including patients with IgA nephropathy. He did BSc in Biomedical Sciences from London University and MB MS, from Middlesex Hospital Medical School.