STOCKHOLM, Aug. 18,
2023 /PRNewswire/ -- Calliditas Therapeutics
AB (Nasdaq: CALT), (Nasdaq Stockholm: CALTX) ("Calliditas"),
today announced that the U.S. Food and Drug Administration (FDA)
has accepted the submission for the supplemental New Drug
Application (sNDA) for TARPEYO® (budesonide)
delayed release capsules and granted Priority Review. The
Prescription Drug User Fee Act (PDUFA) goal date is 20 December 2023.
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.
"We are delighted to have been granted priority review by the
FDA, which brings us one step closer to hopefully being able to
provide TARPEYO to all patients at risk of progression and provide
physicians with a tool to target the source of this disease to slow
kidney function decline," said Renee
Aguiar-Lucander, CEO of Calliditas. "The significant eGFR
treatment benefit observed across the entire study population
provides further evidence that TARPEYO can be disease-modifying,
potentially significantly delaying the need for dialysis or kidney
transplantation for patients at risk."
The sNDA is based on the full data set from the Phase 3 NefIgArd
clinical trial, a randomized, double-blind, multicenter study
evaluating the efficacy and safety of TARPEYO (developed under the
project name Nefecon®) at a once-daily dose of 16 mg, compared to
placebo, in adult patients with primary IgAN on optimized RASi
therapy. The trial demonstrated a statistically significant benefit
of Nefecon over placebo (p-value < 0.0001) in estimated
glomerular filtration rate (eGFR) over the two-year study period,
which consisted of nine months of treatment with Nefecon or
placebo, followed by a 15-month follow-up period off the study
drug. The data reflected treatment benefits across the entire study
population, regardless of UPCR baseline, and showed a difference
between TARPEYO and placebo in 2-year eGFR total slope of
approximately 3mL/min per year using a robust regression method of
analysis.
"We take great pride in the strong clinical evidence we have
gathered, which we believe demonstrates TARPEYO's durable and
clinically meaningful impact on kidney function in the treatment of
IgAN," commented Richard Phillipson,
Chief Medical Officer at Calliditas. "The combination of the
significant eGFR benefit and the reduction in proteinuria lasting
for the entire 15-month follow-up period in the full results of our
Phase 3 study provide strong rationale for establishing TARPEYO as
the standard of care for IgAN patients."
Calliditas is also collaborating with its European commercial
partner, STADA Arzneimettel AG, to seek full approval of Nefecon
(which received conditional approval under the brand name
Kinpeygo®) by the European Commission in the full study
population.
For further information, please contact:
Åsa Hillsten, Head of Investor Relations, Calliditas
Tel.: +46 76 403 35 43, email: asa.hillsten@calliditas.com
The information in the press release is information that
Calliditas is obliged to make public pursuant to the EU Market
Abuse Regulation. The information was sent for publication, through
the agency of the contact persons set out above, on August 18, 2023 at 10:00
a.m. CET.
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 TARPEYO
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. 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.
About Calliditas
Calliditas Therapeutics is a commercial stage biopharma company
based 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' lead
product, developed under the name Nefecon, has been granted
accelerated approval by the FDA under the trade name TARPEYO® and
conditional marketing authorization by the European Commission
under the trade name Kinpeygo®. Kinpeygo is being commercialized in
the European Union Member States by Calliditas' partner, STADA
Arzneimittel AG. Additionally, Calliditas is conducting a Phase
2b/3 clinical trial in primary
biliary cholangitis and a Phase 2 proof-of-concept trial in head
and neck cancer with its NOX inhibitor product candidate,
setanaxib. Calliditas' common shares are listed on Nasdaq Stockholm
(ticker: CALTX) and its American Depositary Shares are listed on
the Nasdaq Global Select Market (ticker: CALT).
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, commercialization efforts, business
plans, regulatory submissions, clinical development plans, revenue
and product sales projections or forecasts 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 and additional regulatory approvals for TARPEYO and
Kinpeygo, market acceptance of TARPEYO and Kinpeygo, clinical
trials, supply chain, strategy, goals and anticipated timelines,
competition from other biopharmaceutical companies, revenue and
product sales projections or forecasts 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.
The following files are available for download:
https://mb.cision.com/Main/16574/3819643/2235284.pdf
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