Pressreleaser | 19 Sep 2023 | Calliditas Therapeutics

Calliditas Therapeutics to Present Nefecon Data at the 17[th] International Symposium on IgA Nephropathy (IIgANN) September 25-27 in Tokyo

Investigators will be presenting additional analyses of the Phase 3 NefIgArd study’s 2-year data with Nefecon (TARPEYO[®] (budesonide) delayed-release capsules/Kinpeygo[®]) for the treatment of Primary IgA nephropathy (IgAN), along with the biomarker data from the NeflgArd study. IIgANN will be held virtually and in person in Tokyo, Japan, September 25-27, 2023.

Poster presentation details are below and will be available on the Presentation and Publication page on the Calliditas’ corporate website following the meeting. 

Oral Presentation Details:

Title: Analysis of the NefIgArd Part A study population confirms Nefecon suppresses circulating levels of BAFF, APRIL, and soluble BCMA in IgA nephropathy

Presenter: Nadia Nawaz, University of Leicester

Date and Time: Thursday, September 28, 14:35 – 15:35 p.m. JST

Title: Nefecon treatment response in Asian and White patient populations with immunoglobulin A nephropathy: A 2-year analysis of the phase III NefIgArd trial

Presenter: Jonathan Barratt, M.B.Ch.B., Ph.D., University of Leicester

Date and Time: Saturday, September 30, 10:55 – 11:55 a.m. JST

Title: Hematuria reduction in patients with IgAN following Nefecon treatment: A secondary analysis of the full 2-year NefIgArd Phase III trial results

Presenter: Richard Lafayette, M.D., F.A.C.P., Stanford Healthcare

Date and Time: Saturday, September 30, 10:55 – 11:55 a.m. JST

Poster Presentation Details:

Title: Long-term renal benefit over 2 years with Nefecon verified: The NefIgArd Phase III full trial results

Authors: Richard Lafayette, Jens Kristensen, Andrew Stone, Jürgen Floege, Vladimir Tesar, Hernán Trimarchi, Hong Zhang, Necmi Eren, Alexander Paliege, Heather N. Reich, Brad H. Rovin, and Jonathan Barratt

Date and Time: Friday, September 29, 11:20 a.m. – 12:35 p.m. JST

Title: Durable proteinuria reduction over 2 years with Nefecon treatment: A secondary analysis of the full NefIgArd Phase III trial results

Authors: Richard Lafayette, Jens Kristensen, Andrew Stone, Jürgen Floege, Vladimir Tesar, Hernán Trimarchi, Hong Zhang, Necmi Eren, Alexander Paliege, Heather N. Reich, Brad H. Rovin, and Jonathan Barratt

Date and Time: Friday, September 29, 11:20 a.m. – 12:35 p.m. JST

Title: Analysis of the NefIgArd Part A study population confirms Nefecon suppresses circulating levels of IgA-containing immune complexes in IgA nephropathy

Authors: Vicky Cotton, Nadia Nawaz, Karen Molyneux, and Jonathan Barratt

Date and Time: Friday, September 29, 11:20 a.m. – 12:35 p.m. JST

Title: Analysis of the NefIgArd Part A study population confirms that Nefecon modulates circulating levels of the chemokines CXCL5, CCL11, and CCL13 in IgA nephropathy

Authors: Roisin Thomas, Nadia Nawaz, Karen Molyneux, and Jonathan Barratt

Date and Time: Friday, September 29, 11:20 a.m. – 12:35 p.m. JST

For more information, visit the IIgANN website here. ( https://www.m-toyou.com/iigann2023/ )

Indication

TARPEYO[®] (budesonide) delayed release capsules is a corticosteroid indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g.

This indication is approved under accelerated approval based on a reduction in proteinuria. It has not been established whether TARPEYO slows kidney function decline in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefits in a confirmatory clinical trial.

Important Safety Information

Contraindications: TARPEYO is contraindicated in patients with hypersensitivity to budesonide or any of the ingredients of TARPEYO. Serious hypersensitivity reactions, including anaphylaxis, have occurred with other budesonide formulations.

Warnings and Precautions

Hypercorticism and adrenal axis suppression: When corticosteroids are used chronically, systemic effects such as hypercorticism and adrenal suppression may occur. Corticosteroids can reduce the response of the hypothalamus-pituitary-adrenal (HPA) axis to stress. In situations where patients are subject to surgery or other stress situations, supplementation with a systemic corticosteroid is recommended. When discontinuing therapy [see Dosing and Administration] or switching between corticosteroids, monitor for signs of adrenal axis suppression.

Patients with moderate to severe hepatic impairment (Child-Pugh Class B and C, respectively) could be at an increased risk of hypercorticism and adrenal axis suppression due to an increased systemic exposure to oral budesonide. Avoid use in patients with severe hepatic impairment (Child-Pugh Class C). Monitor for increased signs and/or symptoms of hypercorticism in patients with moderate hepatic impairment (Child-Pugh Class B).

Risks of immunosuppression: Patients who are on drugs that suppress the immune system are more susceptible to infection than healthy individuals. Chicken pox and measles, for example, can have a more serious or even fatal course in susceptible patients or patients on immunosuppressive doses of corticosteroids. Avoid corticosteroid therapy in patients with active or quiescent tuberculosis infection; untreated fungal, bacterial, systemic viral, or parasitic infections; or ocular herpes simplex. Avoid exposure to active, easily transmitted infections (eg., chicken pox, measles). Corticosteroid therapy may decrease the immune response to some vaccines.

Other corticosteroid effects: TARPEYO is a systemically available corticosteroid and is expected to cause related adverse reactions. Monitor patients with hypertension, prediabetes, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma, cataracts, a family history of diabetes or glaucoma, or with any other condition in which corticosteroids may have unwanted effects.

Adverse reactions: In clinical studies, the most common adverse reactions with TARPEYO (occurring in ≥5% of TARPEYO patients and ≥2% higher than placebo) were hypertension (16%), peripheral edema (14%), muscle spasms (13%), acne (11%), dermatitis (7%), weight increase (7%), dyspnea (6%), face edema (6%), dyspepsia (5%), fatigue (5%), and hirsutism (5%).

Drug interactions: Budesonide is a substrate for CYP3A4. Avoid use with potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin, and cyclosporine. Avoid ingestion of grapefruit juice with TARPEYO. Intake of grapefruit juice, which inhibits CYP3A4 activity, can increase the systemic exposure to budesonide.

Use in specific populations

Pregnancy: The available data from published case series, epidemiological studies, and reviews with oral budesonide use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with IgAN. Infants exposed to in utero corticosteroids, including budesonide, are at risk for hypoadrenalism.

Please see Full Prescribing Information ( https://www.tarpeyohcp.com/prescribinginformation.pdf ).

About TARPEYO[1]

Calliditas has introduced TARPEYO, the first FDA-approved therapy for the treatment of the autoimmune renal disease primary IgA Nephropathy, or IgAN, to reduce proteinuria in adults with primary IgAN who are at risk of rapid disease progression, generally a UPCR≥1.5g/g. This indication is approved under accelerated approval based on a reduction in proteinuria. It has not been established whether TARPEYO slows kidney function decline in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial.

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. TARPEYO is as a 4 mg delayed release capsule and is enteric coated and designed to remain intact until it reaches the ileum. Each capsule contains coated beads of budesonide that target mucosal B-cells present in the ileum, including the Peyer’s patches, which are responsible for the production of galactose-deficient IgA1 antibodies (Gd-Ag1) causing IgA nephropathy. It is unclear to what extent TARPEYO’s efficacy is mediated via local effects in the ileum vs systemic effects.

About the NeflgArd Study

The global clinical trial NefIgArd is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of TARPEYO 16 mg once daily vs placebo in adult patients with primary IgAN (N=364), as an addition to optimized RAS inhibitor therapy. Part A of the study included a 9-month blinded treatment period and a 3-month follow-up period. The primary endpoint was UPCR, and eGFR was a secondary endpoint. Part B included a 12-month observational period off drug and assessed eGFR over the entire 2-year period for patients who were treated with the TARPEYO or placebo regimen in Part A. The full NefIgArd trial met its primary endpoint. Topline data from the full NefIgArd study were reported on March 12, 2023.

About Primary Immunoglobulin A Nephropathy

Primary immunoglobulin A nephropathy (IgA nephropathy or IgAN or Berger’s Disease) is a rare, progressive, chronic autoimmune disease that attacks the kidneys and occurs when galactose-deficient IgA1 is recognized by autoantibodies, creating IgA1 immune complexes that become deposited in the glomerular mesangium of the kidney.[2,3] This deposition in the kidney can lead to progressive kidney damage and potentially a clinical course resulting in end- stage renal disease. IgAN most often develops between late teens and late 30s.[3,4]

About Calliditas

Calliditas Therapeutics is a biopharma company headquartered in Stockholm, Sweden, focused on identifying, developing, and commercializing novel treatments in orphan indications, with an initial focus on renal and hepatic diseases with significant unmet medical needs.

Calliditas is listed on Nasdaq Stockholm (ticker: CALTX) and the Nasdaq Global Select Market (ticker: CALT).

Visit Calliditas.com ( http://www.calliditas.com/ ) for further information.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding Calliditas’ strategy, business plans, regulatory submissions, and focus. The words ”may,” ”will,” ”could,” ”would,” ”should,” ”expect,” ”plan,” ”anticipate,” ”intend,” ”believe,” ”estimate,” ”predict,” ”project,” ”potential,” ”continue,” ”target,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties, and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, any related to Calliditas’ business, operations, continued FDA approval for TARPEYO, the potential to expand TARPEYO’s FDA approval to the entire Phase 3 study population, the potential to achieve full approval of Kinpeygo from the EC and MHRA, market acceptance of TARPEYO, clinical trials, supply chain, strategy, goals and anticipated timelines, competition from other biopharmaceutical companies, and other risks identified in the section entitled ”Risk Factors” in Calliditas’ reports filed with the Securities and Exchange Commission. Calliditas cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. Calliditas disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions, or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent Calliditas’ views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date.

For further information, please contact:

Åsa Hillsten, Head of IR & Sustainability, Calliditas

Tel.: +46 76 403 35 43, email: asa.hillsten@calliditas.com

The information was sent for publication, through the agency of the contact person set out above, on September 19, 2023, at 4.00 p.m. CET.

[1]  TARPEYO[®] (budesonide) [prescribing information]. Stockholm, SE: Calliditas Therapeutics AB; 2021

[2]  Barratt, J., & Feehally, J. (2005). IgA nephropathy. J Am Soc Nephrol, 16(7), 2088-2097. https://doi.org/10.1681/ASN.2005020134

 [3] Barratt, J., Rovin, B. H., Cattran, D., et al. (2020). Why Target the Gut to Treat IgA Nephropathy? Kidney Int Rep, 5(10), 1620-1624.  https://doi.org/10.1016/j.ekir.2020.08.009

[4]  Jarrick, S., Lundberg, S., Welander, A., et al. (2019). Mortality in IgA Nephropathy: A Nationwide Population-Based Cohort Study. J Am Soc Nephrol, 30(5), 866-876. https://doi.org/10.1681/ASN.2018101017