STOCKHOLM, June 21,
2023 /PRNewswire/ -- Calliditas Therapeutics
AB (Nasdaq: CALT) (Nasdaq Stockholm: CALTX) ("Calliditas")
today announced the submission of a supplemental New Drug
Application ("sNDA") to the U.S. Food and Drug Administration
("FDA") seeking full approval of
TARPEYO® (budesonide) delayed release capsules for
the entire study population from the Phase 3 NeflgArd
study.
TARPEYO is currently approved under accelerated approval to
reduce proteinuria in adults with primary IgA nephropathy ("IgAN")
at risk of rapid disease progression, generally a urine
protein-to-creatinine ratio (UPCR) ≥1.5g/g.
The sNDA submission is based on the full data set from the Phase
3 NefIgArd clinical trial, a randomized, double-blind, multicenter
study which assessed the efficacy and safety of TARPEYO (developed
under the project name Nefecon®) dosed at 16 mg once daily versus
placebo on a background of optimized RASi therapy in adult patients
with primary IgAN. The trial met its primary endpoint, with TARPEYO
demonstrating a highly statistically significant benefit over
placebo (p value < 0.0001) in estimated glomerular filtration
rate (eGFR) over the two-year period of 9-months of treatment with
TARPEYO or placebo and 15-months of follow-up off drug.
"The eGFR treatment benefit observed across the entire study
population, irrespective of UPCR levels, provides further evidence
that targeting IgAN at its source can offer patients a treatment
that holds the promise of being disease modifying. We are pleased
to be able to provide the FDA with the full results of our Phase 3
study, and we look forward to interactions with the FDA regarding
full approval of TARPEYO," stated Renée Aguiar-Lucander, Chief
Executive Officer of Calliditas Therapeutics.
In addition to the U.S. FDA submission, Calliditas is
collaborating with its European commercial partner, STADA
Arzneimettel AG, to seek full approval of Nefecon (branded as
Kinpeygo®) by the European Commission in the full study
population.
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.
About TARPEYO1
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 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, Calliditas
Tel.: +46 76 403 35 43,
email: asa.hillsten@calliditas.com
The information was sent for publication, through the agency
of the contact persons set out above, on June 21, 2023 at 9.00 a.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
The following files are available for download:
https://mb.cision.com/Main/16574/3791122/2143383.pdf
|
CALT_sNDA_Submission
Eng
|
View original
content:https://www.prnewswire.com/news-releases/calliditas-therapeutics-submits-supplemental-new-drug-application-to-us-food-and-drug-administration-for-full-approval-of-tarpeyo-301856435.html
SOURCE Calliditas Therapeutics