Talicia's efficacy and safety profile evaluated in patients
with H. pylori infection and diabetes mellitus, a large and
challenging patient population associated with sub-optimal outcomes
with clarithromycin-based H. pylori eradication therapy
Physiologically based pharmacokinetic modeling study of
Talicia evaluated intragastric antibiotic exposure, which is
critical for successful H. pylori eradication, by comparing
low-dose rifabutin 50 mg every 8 hours to the generic formulation
of rifabutin 150 mg once a day
Talicia, the leading FDA-approved brand for H. pylori
treatment, is intended for empiric first-line eradication of H.
pylori, a bacterial infection that affects approximately 35% of the
U.S. adult population, representing significant unmet need
RALEIGH,
N.C. and TEL AVIV,
Israel, May 25, 2022 /PRNewswire/ -- RedHill
Biopharma Ltd. (NASDAQ: RDHL) ("RedHill" or the "Company"), a
specialty biopharmaceutical company, announced the presentation of
two new data analyses from the Talicia® H. pylori
eradication clinical trials program at Digestive Diseases Week
(DDW) 2022.
The first analysis evaluated the maintenance of Talicia's
efficacy and safety in the treatment of patients with H.
pylori infection and diabetes mellitus (DM). DM is associated
with higher rates of H. pylori infection and higher rates of
treatment failure with clarithromycin-based therapies. Furthermore,
clarithromycin interacts with some common diabetes medications
potentially leading to hypoglycemia1.
The second analysis, a physiologically based pharmacokinetic
(PBPK) study, used modeling to compare Talicia's low-dose rifabutin
formulation's (rifabutin 50 mg every 8 hours) sustained
intragastric antibiotic exposure, a critical component of
successful H. pylori eradication, to exposure rates seen
with the generic formulation of rifabutin (150 mg taken once daily
(QD).
Poster one (poster number: Tu1078): Low-Dose Rifabutin
Triple Therapy (Talicia) Maintains High Helicobacter pylori
Eradication Rates and Shows Favorable Safety and Efficacy in
Subjects with Diabetes Mellitus.
Presenting Author: Dr. Colin W.
Howden, MD, Professor Emeritus, University of Tennessee Health Science Center
This supplemental analysis of the pooled modified
intent-to-treat (mITT) population (n=293) from two Phase 3 clinical
trials (ERADICATE Hp, ERADICATE Hp2) assessed the safety and
efficacy of Talicia in patients with DM. H. pylori isolates
from treatment-naïve patients from study 2 were also tested for
antibiotic resistance according to the presence of DM. The 293
patient-analyzable mITT population who received Talicia had pooled
eradication rates of 91.7% (n=44) and 84.1% (n=206) in patients
with and without DM, respectively (p=0.17). Moreover, no
resistance was seen to rifabutin in patients with or without DM.
Resistance rates were 4% v 7% for amoxicillin, 45% v 43% for
metronidazole, and 21% v 17% resistance to clarithromycin in
patients with and without DM, respectively. With the exception
of an observed higher rate of diarrhea in patients without diabetes
versus those with (13.8% vs 6%), the presence of diabetes did not
alter the safety or tolerability of Talicia, and generally matched
the safety profile of the total patient population.
"More than 37 million Americans have diabetes, which presents
significant issues in the treatment of H. pylori infection.
Firstly, we know that the risk of treatment failure with
clarithromycin-based therapies is significantly higher in patients
with diabetes2, and secondly, the use of clarithromycin
in diabetic patients can impair the management of their diabetes
due to drug-drug interactions," said Dr. Barry Johns, MD, from The Jones Center for
Diabetes and Endocrine Wellness, Macon,
GA. "Consequently, it is vital that we know which
therapies are most appropriate for first-line H. pylori
eradication treatment. Since Talicia maintains high eradication
rates and is well tolerated regardless of a patient's diabetes, it
represents a rational empiric first-line choice for the treatment
of H. pylori infection."
Poster two (poster number: Tu1077): Low-Dose Rifabutin
Triple Therapy Demonstrates High Helicobacter pylori
Eradication Rates: Physiologically-Based Pharmacokinetic (PBPK)
Modeling Supports Favorable Intragastric Rifabutin Concentrations
for 50 mg Q8H Dosing vs. 150 mg QD
Presenting Author: Dr. Colin W.
Howden, MD, Professor Emeritus, University of Tennessee Health Science Center.
Sufficient intragastric antibiotic exposure is critical for
eradication of H. pylori. Consequently, understanding the
influence of antibiotic dosing on intragastric exposure is
imperative. This study used PBPK modeling to compare intragastric
rifabutin concentrations with Talicia (low-dose rifabutin 50 mg)
administered every 8 hours (Q8H) vs. rifabutin 150 mg (the
generically available dose) administered once daily (QD).
Intragastric rifabutin concentration time above the mean inhibitory
concentration (MIC90 = 0.008 mcg/mL) was calculated over
a 24-hour period for each regimen. Low-dose rifabutin 50 mg Q8H, as
in Talicia, maintained intragastric rifabutin concentrations at or
above the MIC90 for approximately three times longer
than rifabutin 150 mg QD. When taken with food (as indicated in the
prescribing information), low-dose rifabutin 50 mg Q8H, as in
Talicia, provided intragastric concentrations at or above the
MIC90 for about 93% of the day, compared to 35% of the
day when dosed as 150 mg QD.
"Maintaining high intragastric antibiotic concentrations is
necessary for successful H. pylori eradication. Dosing
rifabutin at 150 mg QD does not replicate the sustained
intragastric concentrations predicted with low-dose rifabutin at 50
mg Q8H. The differences in intragastric exposure seen in this study
may potentially explain the lower and less consistent eradication
rates seen with generic rifabutin (about 70% eradication) than seen
in the Talicia clinical trial program (about 84-90% eradication),"
said Dr. Colin W. Howden, MD,
Professor Emeritus, University of
Tennessee Health Science Center. "Given the need to aim for
the most effective empiric first-line eradication therapy, it is
important to utilize a therapy with the highest likelihood of H.
pylori eradication success, such as Talicia."
"These important new data enhance the body of evidence
supporting the use of Talicia as a first line therapy for H.
pylori," said Dr. June
Almenoff, MD, Ph.D., RedHill's Chief Medical Officer.
"Talicia consistently shows its ability to maintain high H.
pylori eradication rates, even in challenging patient
populations, with zero to minimal resistance. This work also
demonstrates Talicia's sustained intragastric exposure, providing
optimized conditions for eradication of H. pylori at the
first treatment attempt."
About H. pylori infection
H.
pylori is a bacterial infection that affects approximately
35%3 of the U.S. population, with an estimated two
million patients treated annually4. Worldwide, more than
50% of the population has H. pylori infection, which is
classified by the WHO as a Group 1 carcinogen. It remains the
strongest known risk factor for gastric cancer5 and a
major risk factor for peptic ulcer disease6 and gastric
mucosa-associated lymphoid tissue (MALT) lymphoma7. More
than 27,000 Americans are diagnosed with gastric cancer
annually8. Eradication of H. pylori is
becoming increasingly difficult, with current therapies failing in
approximately 25-40% of patients who remain H.
pylori-positive due to high resistance of H.
pylori to antibiotics – especially clarithromycin – which
is still commonly used in standard combination
therapies9.
About
Talicia®
Talicia® is the only low-dose rifabutin-based therapy
approved for the treatment of H. pylori infection and is
designed to address the high resistance of H. pylori
bacteria seen with other antibiotics. The high rates of H.
pylori resistance to clarithromycin have led to
significant rates of treatment failure with clarithromycin-based
therapies and are a strong public health concern, as highlighted by
the ACG, FDA and the World Health Organization (WHO) in recent
years.
Talicia® is a novel, fixed-dose, all-in-one oral
capsule combination of two antibiotics (amoxicillin and rifabutin)
and a proton pump inhibitor (PPI) (omeprazole). In November 2019, Talicia® was approved
by the U.S. FDA for the treatment of H. pylori infection in
adults. In the pivotal Phase 3 study, Talicia®
demonstrated 84% eradication of H. pylori infection in the
intent-to-treat (ITT) group vs. 58% in the active comparator arm
(p<0.0001). Minimal to zero resistance to rifabutin, a key
component of Talicia®, was detected in RedHill's pivotal Phase 3
study. Further, in an analysis of data from this study, it was
observed that subjects who were confirmed adherent10 to
their therapy had response rates of 90.3% in the
Talicia® arm vs. 64.7% in the active comparator
arm11. Talicia® is eligible for a total of
eight years of U.S. market exclusivity under its Qualified
Infectious Disease Product (QIDP) designation and is also covered
by U.S. patents which extend patent protection until 2034 with
additional patents and applications pending and granted in various
territories worldwide.
About RedHill Biopharma
RedHill Biopharma
Ltd. (NASDAQ: RDHL) is a specialty biopharmaceutical company
primarily focused on gastrointestinal and infectious diseases.
RedHill promotes the gastrointestinal drugs,
Movantik® for opioid-induced constipation in
adults12, Talicia® for the
treatment of Helicobacter pylori (H. pylori) infection in
adults13, and Aemcolo® for
the treatment of travelers' diarrhea in
adults14. RedHill's key clinical late-stage
development programs include: (i) RHB-204, with an
ongoing Phase 3 study for pulmonary nontuberculous mycobacteria
(NTM) disease; (ii) opaganib (ABC294640), a
first-in-class oral SK2 selective inhibitor targeting
multiple indications with a Phase 2/3 program for hospitalized
COVID-19 and Phase 2 studies for prostate cancer and
cholangiocarcinoma ongoing; (iii) RHB-107
(upamostat), an oral serine protease inhibitor in a Phase
2/3 study as treatment for non-hospitalized symptomatic COVID-19,
and targeting multiple other cancer and inflammatory
gastrointestinal diseases; (iv) RHB-104, with positive
results from a first Phase 3 study for Crohn's disease; (v)
RHB-102 , with positive results from a Phase 3 study for
acute gastroenteritis and gastritis and positive results from a
Phase 2 study for IBS-D; and (vi) RHB-106, an
encapsulated bowel preparation. More information about the Company
is available at www.redhillbio.com/ twitter.com/RedHillBio.
TALICIA: INDICATION AND IMPORTANT SAFETY
INFORMATION
Talicia is a three-drug combination of
omeprazole, a proton pump inhibitor, amoxicillin, a
penicillin-class antibacterial, and rifabutin, a rifamycin
antibacterial, indicated for the treatment
of Helicobacter pylori infection in
adults.
To reduce the development of drug-resistant bacteria and maintain
the effectiveness of Talicia and other antibacterial drugs, Talicia
should be used only to treat or prevent infections that are proven
or strongly suspected to be caused by bacteria.
IMPORTANT SAFETY INFORMATION
Talicia contains
omeprazole, a proton pump inhibitor (PPI), amoxicillin, a
penicillin-class antibacterial and rifabutin, a rifamycin
antibacterial. It is contraindicated in patients with known
hypersensitivity to any of these medications, any other components
of the formulation, any other beta-lactams or any other
rifamycin.
Talicia is contraindicated in patients receiving
rilpivirine-containing products.
Talicia is contraindicated in patients receiving delavirdine or
voriconazole.
Serious and occasionally fatal hypersensitivity reactions have
been reported with omeprazole, amoxicillin and rifabutin.
Severe cutaneous adverse reactions (SCAR) (e.g., Stevens-Johnson
syndrome (SJS), Toxic epidermal necrolysis (TEN)) have been
reported with rifabutin, amoxicillin, and omeprazole. Additionally,
drug reaction with eosinophilia and systemic symptoms (DRESS) has
been reported with rifabutin.
Acute Tubulointerstitial Nephritis has been observed in patients
taking PPIs and penicillins.
Clostridioides difficile-associated diarrhea (CDAD) has
been reported with use of nearly all antibacterial agents and may
range from mild diarrhea to fatal colitis.
Talicia may cause fetal harm. Talicia is not recommended for use in
pregnancy. Talicia may reduce the efficacy of hormonal
contraceptives. An additional non-hormonal method of contraception
is recommended when taking Talicia.
Talicia should not be used in patients with hepatic impairment
or severe renal impairment.
Cutaneous lupus erythematosus (CLE) and systemic lupus
erythematosus (SLE) have been reported in patients taking PPIs.
These events have occurred as both new onset and exacerbation of
existing autoimmune disease.
The most common adverse reactions (≥1%) were diarrhea, headache,
nausea, abdominal pain, chromaturia, rash, dyspepsia, oropharyngeal
pain, vomiting, and vulvovaginal candidiasis.
To report SUSPECTED ADVERSE REACTIONS, contact RedHill Biopharma
INC. at
1-833-ADRHILL (1-833-237-4455) or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
Full prescribing information for Talicia is available
at www.Talicia.com
This press release contains "forward-looking statements"
within the meaning of the Private Securities Litigation Reform Act
of 1995. Such statements may be preceded by the words "intends,"
"may," "will," "plans," "expects," "anticipates," "projects,"
"predicts," "estimates," "aims," "believes," "hopes," "potential"
or similar words. Forward-looking statements are based on certain
assumptions and are subject to various known and unknown risks and
uncertainties, many of which are beyond the Company's control and
cannot be predicted or quantified, and consequently, actual results
may differ materially from those expressed or implied by such
forward-looking statements. Such risks and uncertainties, including
without limitation risks regarding the treatment effectiveness of
Talicia and the risk that the Company will not succeed to expand
Talicia's reach to additional ex-U.S. territories; as well as other
risk and uncertainties associated with (i) the initiation, timing,
progress and results of the Company's research, manufacturing,
pre-clinical studies, clinical trials, and other therapeutic
candidate development efforts, and the timing of the commercial
launch of its commercial products and ones it may acquire or
develop in the future; (ii) the Company's ability to advance its
therapeutic candidates into clinical trials or to successfully
complete its pre-clinical studies or clinical trials; (iii) the
extent and number and type of additional studies that the Company
may be required to conduct and the Company's receipt of regulatory
approvals for its therapeutic candidates, and the timing of other
regulatory filings, approvals and feedback; (iv) the manufacturing,
clinical development, commercialization, and market acceptance of
the Company's therapeutic candidates and Talicia®; (v)
the Company's ability to successfully commercialize and promote
Talicia®, Aemcolo® and Movantik®;
(vi) the Company's ability to establish and maintain corporate
collaborations; (vii) the Company's ability to acquire products
approved for marketing in the U.S. that achieve commercial success
and build its own marketing and commercialization capabilities;
(viii) the interpretation of the properties and characteristics of
the Company's therapeutic candidates and the results obtained with
its therapeutic candidates in research, pre-clinical studies or
clinical trials; (ix) the implementation of the Company's business
model, strategic plans for its business and therapeutic candidates;
(x) the scope of protection the Company is able to establish and
maintain for intellectual property rights covering its therapeutic
candidates and its ability to operate its business without
infringing the intellectual property rights of others; (xi) parties
from whom the Company licenses its intellectual property defaulting
in their obligations to the Company; (xii) estimates of the
Company's expenses, future revenues, capital requirements and needs
for additional financing; (xiii) the effect of patients suffering
adverse experiences using investigative drugs under the Company's
Expanded Access Program; and (xiv) competition from other companies
and technologies within the Company's industry. More detailed
information about the Company and the risk factors that may affect
the realization of forward-looking statements is set forth in the
Company's filings with the Securities and Exchange Commission
(SEC), including the Company's Annual Report on Form 20-F filed
with the SEC on March 17, 2022. All forward-looking
statements included in this press release are made only as of the
date of this press release. The Company assumes no obligation to
update any written or oral forward-looking statement, whether as a
result of new information, future events or otherwise unless
required by law.
Company
contact:
Adi Frish
Chief Corporate &
Business Development Officer
RedHill
Biopharma
+972-54-6543-112
adi@redhillbio.com
|
Media contacts:
U.S. / UK: Amber Fennell, Consilium
+44 (0) 7739 658 783
fennell@consilium-comms.com
|
[1] Kennedy KE, Teng C, Patek TM, Frei CR. Hypoglycemia
Associated with Antibiotics Alone and in Combination with
Sulfonylureas and Meglitinides: An Epidemiologic Surveillance Study
of the FDA Adverse Event Reporting System (FAERS). Drug Saf. 2020
Apr;43(4):363-369. doi: 10.1007/s40264-019-00901-7. PMID: 31863282;
PMCID: PMC7117991.
[2] Chey WD, et al. ACG Clinical Guideline: Treatment of
Helicobacter pylori Infection [published correction appears in Am J
Gastroenterol. 2018 Jul;113(7):1102]. Am J Gastroenterol.
2017;112(2):212-239.
Horikawa C, et al. High risk of failing eradication of
Helicobacter pylori in patients with diabetes: a meta-analysis.
Diabetes Res Clin Pract. 2014;106(1):81-87.
[3] Hooi JKY et al. Global Prevalence of Helicobacter
pylori Infection: Systematic Review and Meta-Analysis.
Gastroenterology 2017; 153:420-429.
[4] IQVIA Custom Study for RedHill Biopharma, 2019
[5] Lamb A et al. Role of the Helicobacter pylori–Induced
inflammatory response in the development of gastric cancer. J Cell
Biochem 2013;114.3:491-497.
[6] NIH – Helicobacter pylori and Cancer, September
2013.
[7] Hu Q et al. Gastric mucosa-associated lymphoid tissue
lymphoma and Helicobacter pylori infection: a review of
current diagnosis and management. Biomarker research
2016;4.1:15.
[8] National Cancer Institute, Surveillance, Epidemiology, and
End Results Program (SEER).
[9] Malfertheiner P. et al. Management of Helicobacter
pylori infection - the Maastricht IV/ Florence Consensus
Report, Gut 2012;61:646-664; O'Connor A. et al. Treatment
of Helicobacter pylori Infection 2015,
Helicobacter 20 (S1) 54-61; Venerito M. et al. Meta-analysis of
bismuth quadruple therapy versus clarithromycin triple therapy for
empiric primary treatment of Helicobacter
pylori infection. Digestion 2013;88(1):33-45.
[10] Defined as the PK population which included those subjects
in the ITT population who had demonstrated presence of any
component of investigational drug at visit 3 (approx. day 13) or
had undetected levels drawn >250 hours after the last dose.
[11] The pivotal Phase 3 study with Talicia®
demonstrated 84% eradication of H. pylori infection with
Talicia® vs. 58% in the active comparator arm (ITT
analysis, p<0.0001).
[12] Movantik® (naloxegol) is indicated for opioid-induced
constipation (OIC). Full prescribing information see:
www.movantik.com.
[13] Talicia® (omeprazole magnesium, amoxicillin and
rifabutin) is indicated for the treatment of H. pylori
infection in adults. For full prescribing information see:
www.Talicia.com.
[14] Aemcolo® (rifamycin) is indicated for the
treatment of travelers' diarrhea caused by noninvasive strains of
Escherichia coli in adults. For full prescribing information
see: www.aemcolo.com.
View original
content:https://www.prnewswire.com/news-releases/redhill-presents-new-talicia-data-analyses-at-ddw-2022-301554962.html
SOURCE RedHill Biopharma Ltd.