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Analyses Find Patients With
Polycythemia Vera (PV)
Treated With
BESREMi
® (
ropeginterferon alfa-2b
) Had Increased Probability of Achieving Complete Hematologic Response
2024-04-01
·
BioSpace
临床结果
孤儿药
上市批准
临床2期
Analyses published in the British Journal of Clinical Pharmacology suggest a favorable balance between benefits and risks associated with BESREMi BURLINGTON, Mass.--(BUSINESS WIRE)--
PharmaEssentia USA Corporation
, a subsidiary of
PharmaEssentia Corporation
(TWSE: 6446), a global biopharmaceutical innovator based in Taiwan leveraging deep expertise and proven scientific principles to deliver new biologics in hematology and oncology, announced the publication of an original article in the British Journal of Clinical Pharmacology, “Exposure–efficacy and exposure–safety analyses of
ropeginterferon alfa-2b
treatment in patients with
polycythaemia vera
.” Overall, these analyses indicate that patients with
polycythemia vera (PV)
treated with
ropeginterferon alfa-2b
(marketed as
BESREMi
®) had an increased probability of achieving complete hematologic response (CHR) and a molecular response with acceptable safety risks when using a 250–350–500 µg dosing regimen. Writing and editorial support were funded by
PharmaEssentia
, however authors retained full editorial control and provided final approval on all content. Among key findings, patients with PV treated with
ropeginterferon alfa-2b
had an increased probability of achieving CHR and reducing JAK2V617F allele burden with acceptable safety risks. The exposure–safety population was comprised of 49 patients from the Phase 2 Chinese study (A20-202). In this study, of the high-frequency treatment-related adverse events (TRAEs), only increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were observed to be associated with average
ropeginterferon
alfa-2b exposure in the 500 µg phase. "Our exposure-efficacy modeling further demonstrates the effectiveness of
ropeginterferon alfa-2b
in achieving CHR and reducing the JAK2V617F allele burden for patients with PV,” said Albert Qin, M.D., Ph.D., Chief Medical Officer at
PharmaEssentia Corporation
and lead study author. “As we continue to advance
ropeginterferon alfa-2b
as a valuable treatment option for patients with PV, these models reinforce the favorable benefit/risk pro with the 250-350-500 µg dosing schedule which has a flexibility of dose adjustment according to tolerability.” More About this Analysis In this study, exposure–response (E-R) analyses were performed to evaluate the efficacy and safety of the dosing regimens, based on the results of the Chinese A20-202 study evaluating subcutaneous
ropeginterferon alfa-2b
in patients with PV. The treatment protocol included a starting dose of 250 µg at Week 0, followed by an intra-patient dose escalation to 350 µg at Week 2 and then a target dose of 500 µg at Week 4. The dose could be adjusted according to tolerability, and the maintenance dose was 500 μg for up to 52 weeks if tolerated. The primary endpoint was the CHR rate at Week 24. Key secondary endpoints included the reduction of the JAK2V617F allele burden and safety. The safety variable was TRAEs. The E-R analyses were based on logistic and linear regression and the relationship between exposure to
ropeginterferon alfa-2b
and key efficacy and safety variables. The population for the exposure efficacy analysis included 48 patients from the A20-202 trial who had both CHR and JAK2V617F allele burden measurements at Week 24. The final exposure–CHR model structure for the A20-202 study demonstrated that
ropeginterferon alfa-2b
increases the probability of achieving CHR with its dose. The results derived from the E-R model indicated similar CHR probabilities within the third and fourth quantile range of the average concentration at Week 24. Follow
PharmaEssentia USA
on Twitter and LinkedIn for news and updates. About
Polycythemia Vera (PV)
Polycythemia vera (PV)
is a
cancer
originating from a disease-initiating stem cell in the bone marrow resulting in a chronic increase of red blood cells, white blood cells, and platelets. PV may result in cardiovascular complications such as
thrombosis
and
embolism
, and often transforms to
secondary myelofibrosis
or
leukemia
. While the molecular mechanism underlying PV is still subject of intense research, current results point to a set of acquired mutations, the most important being a mutant form of JAK2.1 About
BESREMi
® (
ropeginterferon alfa-2b-njft
)
BESREMi
is an innovative monopegylated, long-acting interferon. With its unique pegylation technology,
BESREMi
has a long duration of activity in the body and is aimed to be administered once every two weeks (or every four weeks with hematological stability for at least one year), allowing flexible dosing that helps meet the individual needs of patients.
BESREMi
has orphan drug designation for the treatment of
polycythemia vera (PV)
in adults in the United States. The product was approved by the
European Medicines Agency (EMA)
in 2019, by the US
Food and Drug Administration (FDA)
in 2021, and has recently received approval in Taiwan and South Korea. The drug candidate was invented by
PharmaEssentia
and is manufactured in the company’s Taichung plant, which was cGMP certified by TFDA in 2017 and by
EMA
in January 2018.
PharmaEssentia
retains full global intellectual property rights for the product in all indications.
BESREMi
was approved with a boxed warning for risk of serious disorders including aggravation of neuropsychiatric, autoimmune, ischemic and infectious disorders. Please see full Prescribing Information, including Boxed Warning. Indication
BESREMi
is indicated for the treatment of adults with
polycythemia vera
. Important Safety Information WARNING: RISK OF SERIOUS DISORDERS Interferon alfa products may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping therapy. CONTRAINDICATIONS Existence of, or history of severe
psychiatric disorders
, particularly severe
depression
,
suicidal ideation
, or suicide attempt Hypersensitivity to interferons including
interferon alfa-2b
or any of the inactive ingredients of
BESREMi
. Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment History or presence of active serious or untreated
autoimmune disease
Immunosuppressed transplant recipients WARNINGS AND PRECAUTIONS
Depression
and
Suicide
: Life-threatening or fatal neuropsychiatric reactions have occurred in patients receiving
interferon alfa-2b
products, including
BESREMi
. These reactions may occur in patients with and without previous
psychiatric illness
. Other central nervous system effects, including
suicidal ideation
,
attempted suicide
,
aggression
,
bipolar disorder
,
mania
and
confusion
have been observed with other
interferon alfa products
. Closely monitor patients for any symptoms of
psychiatric disorders
and consider psychiatric consultation and treatment if such symptoms emerge. If psychiatric symptoms worsen, it is recommended to discontinue
BESREMi
therapy. Endocrine Toxicity: These toxicities may include worsening
hypothyroidism
and
hyperthyroidism
. Do not use
BESREMi
in patients with active serious or untreated
endocrine disorders
associated with
autoimmune disease
. Evaluate thyroid function in patients who develop symptoms suggestive of
thyroid disease
during
BESREMi
therapy. Discontinue
BESREMi
in patients who develop
endocrine disorders
that cannot be adequately managed during treatment with
BESREMi
. Cardiovascular Toxicity: Toxicities may include
cardiomyopathy
,
myocardial infarction
,
atrial fibrillation
and
coronary artery ischemia
. Patients with a history of
cardiovascular disorders
should be closely monitored for cardiovascular toxicity during
BESREMi
therapy. Avoid use of
BESREMi
in patients with severe or
unstable cardiovascular disease
, (e.g.,
uncontrolled hypertension
,
congestive heart failure
(≥ NYHA class 2), serious
cardiac arrhythmia
,
significant coronary artery stenosis
,
unstable angina
) or
recent stroke
or
myocardial infarction
. Decreased Peripheral Blood Counts: These toxicities may include
thrombocytopenia
(increasing the risk of
bleeding
),
anemia
, and
leukopenia
(increasing the risk of
infection
). Monitor complete blood counts at baseline, during titration and every 3-6 months during the maintenance phase. Monitor patients for signs and symptoms of
infection
or
bleeding
.
Hypersensitivity Reactions
: Toxicities may include serious,
acute hypersensitivity reactions
(e.g.,
urticaria
,
angioedema
, bronchoconstriction,
anaphylaxis
). If such reactions occur, discontinue
BESREMi
and institute appropriate medical therapy immediately. Transient rashes may not necessitate interruption of treatment.
Pancreatitis
:
Pancreatitis
has occurred in 2.2% of patients receiving
BESREMi
. Symptoms may include
nausea
,
vomiting
,
upper abdominal pain
, bloating, and
fever
. Patients may experience elevated
lipase
,
amylase
, white blood cell count, or altered renal/hepatic function. Interrupt
BESREMi
treatment in patients with possible
pancreatitis
and evaluate promptly. Consider discontinuation of
BESREMi
in patients with confirmed
pancreatitis
. Colitis: Fatal and serious ulcerative or hemorrhagic/ischemic colitis have occurred in patients receiving
interferon alfa products
, some cases starting as early as 12 weeks after start of treatment. Symptoms may include
abdominal pain
,
bloody diarrhea
, and
fever
. Discontinue
BESREMi
in patients who develop these signs or symptoms.
Colitis
may resolve within 1 to 3 weeks of stopping treatment. Pulmonary Toxicity: Pulmonary toxicity may manifest as
dyspnea
, pulmonary infiltrates,
pneumonia
,
bronchiolitis obliterans
,
interstitial pneumonitis
,
pulmonary hypertension
, and
sarcoidosis
. Some events have resulted in
respiratory failure
or death. Discontinue
BESREMi
in patients who develop pulmonary infiltrates or
pulmonary function impairment
. Ophthalmologic Toxicity: These toxicities may include severe
eye disorders
such as
retinopathy
,
retinal hemorrhage
, retinal exudates,
retinal detachment
and
retinal artery or vein occlusion
which may result in
blindness
. During
BESREMi
therapy, 23% of patients were identified with an
eye disorder
. Eyes disorders ≥5% included
cataract
(6%) and
dry eye
(5%). Advise patients to have eye examinations before and during
BESREMi
therapy, specifically in those patients with a
retinopathy-associated disease
such as
diabetes mellitus
or
hypertension
. Evaluate eye symptoms promptly. Discontinue
BESREMi
in patients who develop new or worsening
eye disorders
.
Hyperlipidemia
: Elevated triglycerides may result in
pancreatitis
. Monitor serum triglycerides before
BESREMi
treatment and intermittently during therapy and manage when elevated. Consider discontinuation of
BESREMi
in patients with persistently, markedly elevated triglycerides. Hepatotoxicity: These toxicities may include increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and bilirubin. Liver enzyme elevations have also been reported in patients after long-term
BESREMi
therapy. Monitor liver enzymes and hepatic function at baseline and during
BESREMi
treatment. Discontinue
BESREMi
in patients who develop evidence of hepatic decompensation (characterized by
jaundice
,
ascites
,
hepatic encephalopathy
,
hepatorenal syndrome
or
variceal hemorrhage
) during treatment. Renal Toxicity: Monitor serum creatinine at baseline and during therapy. Avoid use of
BESREMi
in patients with eGFR <30 mL/min. Discontinue
BESREMi
if severe
renal impairment
develops during treatment. Dental and Periodontal Toxicity: These toxicities may include dental and periodontal disorders, which may lead to loss of teeth. In addition, dry mouth could have a damaging effect on teeth and mucous membranes of the mouth during long-term treatment with
BESREMi
. Patients should have good oral hygiene and regular dental examinations. Dermatologic Toxicity: These toxicities have included
skin rash
,
pruritus
,
alopecia
,
erythema
,
psoriasis
, xeroderma,
dermatitis acneiform
,
hyperkeratosis
, and
hyperhidrosis
. Consider discontinuation of
BESREMi
if clinically significant dermatologic toxicity occurs. Driving and Operating Machinery: BESREMi may impact the ability to drive and use machinery. Patients should not drive or use heavy machinery until they know how
BESREMi
affects their abilities. Patients who experience
dizziness
,
somnolence
or
hallucination
during BESREMi therapy should avoid driving or using machinery. Embryo-Fetal Toxicity: Based on the mechanism of action,
BESREMi
can cause fetal harm when administered to a pregnant woman. Pregnancy testing is recommended in females of reproductive potential prior to treatment with
BESREMi
. Advise females of reproductive potential to use an effective method of contraception during treatment with
BESREMi
and for at least 8 weeks after the final dose. ADVERSE REACTIONS The most common adverse reactions reported in > 40% of patients in the PEGINVERA study (n=51) were
influenza-like illness
,
arthralgia
,
fatigue
,
pruritis
,
nasopharyngitis
, and
musculoskeletal pain
. In the pooled safety population (n=178), the most common adverse reactions greater than 10%, were liver enzyme elevations (20%),
leukopenia
(20%),
thrombocytopenia
(19%),
arthralgia
(13%),
fatigue
(12%),
myalgia
(11%), and
influenza-like illness
(11%). DRUG INTERACTIONS Patients on
BESREMi
who are receiving concomitant drugs which are CYP450 substrates with a narrow therapeutic index should be monitored to inform the need for dosage modification for these concomitant drugs. Avoid use with myelosuppressive agents and monitor patients receiving the combination for effects of excessive
myelosuppression
. Avoid use with narcotics, hypnotics or sedatives and monitor patients receiving the combination for effects of excessive CNS toxicity. USE IN SPECIFIC POPULATIONS Pregnancy: Based on mechanism of action and the role of
interferon alfa
in pregnancy and fetal development,
BESREMi
may cause fetal harm and should be assumed to have abortifacient potential when administered to a pregnant woman. There are adverse effects on maternal and fetal outcomes associated with
polycythemia vera
in pregnancy. Advise pregnant women of the potential risk to a fetus. Lactation: There are no data on the presence of
BESREMi
in human or animal milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children from BESREMi, advise women not to breastfeed during treatment and for 8 weeks after the final dose. Females of Reproductive Potential:
BESREMi
may cause embryo-fetal harm when administered to a pregnant woman. Pregnancy testing prior to
BESREMi
treatment is recommended for females of reproductive potential. Advise female patients of reproductive potential to use effective contraception during treatment with
BESREMi
and for at least 8 weeks after the final dose. Pediatric Use: Safety and effectiveness in pediatric patients have not been established. Geriatric Use: In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other therapy. About
PharmaEssentia
PharmaEssentia
(TPEx: 6446), headquartered in Taipei, Taiwan, is a global and rapidly growing biopharmaceutical innovator. Leveraging deep expertise and proven scientific principles,
PharmaEssentia
aims to deliver effective new biologics for challenging diseases in the areas of hematology, oncology, and immunology with one approved product and a diversifying pipeline. Founded in 2003 by a team of Taiwanese-American executives and renowned scientists from U.S. biotechnology and pharmaceutical companies, today
PharmaEssentia
is expanding its global presence with operations in the U.S., Japan, China, and Korea, along with a world-class biologics production facility in Taichung, Taiwan. For more information about
PharmaEssentia USA
, visit the website, LinkedIn or Twitter. Forward Looking Statement This press release may contain forward looking statements, including statements regarding the clinical benefits to be derived from
ropeginterferon alfa-2b
, the commercial opportunity and competitive positioning, new indications or labeling for
ropeginterferon alfa-2b
, and business prospects for
ropeginterferon alfa-2b
. For those statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995 and similar legislation and regulations under Taiwanese law. These forward-looking statements are based on management expectations and assumptions as of the date of this press release, and actual results may differ materially from those in these forward looking statements as a result of various factors. These factors include whether
BESREMi
is successfully commercialized and adopted by physicians and patients, the extent to which reimbursement is available for
BESREMi
, and the ability to receive
FDA
and other regulatory approvals for additional indications for
BESREMi
. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. © 2024
PharmaEssentia Corporation
. All rights reserved.
PharmaEssentia
, the
PharmaEssentia
logo, and BESREMi are trademarks or registered trademarks of
PharmaEssentia Corporation
. 1 Cerquozzi S, Tefferi A. Blast transformation and fibrotic progression in
polycythemia vera
and
essential thrombocythemia
: a literature review of incidence and risk factors. Blood Cancer J. 2015;5, e366; DOI:10.1038/bcj.2015.95
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机构
药华医药股份有限公司
The European Medicines Agency
US Food & Drug Administration
[+1]
适应症
真性红细胞增多症
肿瘤
血栓形成
[+84]
靶点
Lipase
amylase
药物
Ropeginterferon alfa-2b-NJFT
重组人干扰素α-2b(Merck Sharp & Dohme )
干扰素α (Otsuka Holdings Co., Ltd.)
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