Nipocalimab delayed or prevented severe fetal anemia and 54
percent of study participants in the Phase 2 UNITY study achieved a
live birth at or after 32 weeks without the need for intrauterine
transfusion (IUT)
The AZALEA Phase 3 clinical study is currently enrolling
patients: Nipocalimab is the only therapy in clinical development
for use in pregnancies at risk for severe hemolytic disease of the
fetus and newborn (HDFN)
SPRING HOUSE, Pa., Aug. 7, 2024 /PRNewswire/ -- Johnson &
Johnson (NYSE: JNJ) today announced the results from the Phase 2
open-label UNITY study of nipocalimab for the treatment of
alloimmunizeda pregnant individuals at risk of
early onset severe (EOS) HDFN have been published in The New
England Journal of Medicine (NEJM). The UNITY study met its
primary endpoint with 54 percent of individuals receiving
nipocalimab achieving a live birth at or after 32 weeks gestational
age (GA) without the need for IUT.1 Nipocalimab is
currently the only therapy reported to be in clinical development
for HDFN, a serious and rare condition that occurs when the blood
types of a pregnant individual and the developing fetus are
incompatible, potentially causing life-threatening anemia in the
fetus or infant.2 These results showed
that nipocalimab delayed or prevented severe fetal anemia
requiring treatment prenatally and reduced the need for IUTs in
pregnancies at high risk for recurrent EOS
HDFN.1
![(PRNewsfoto/Johnson & Johnson) (PRNewsfoto/Johnson & Johnson)](https://mma.prnewswire.com/media/2333578/Johnson_and_Johnson_Logo.jpg)
"The Phase 2 data published in the NEJM are encouraging,
as the results support the potential of nipocalimab in the
treatment of pregnant individuals with a history of severe HDFN,
helping to establish a path forward for further development in this
disease in a larger scale Phase 3 study," said Kenneth J. Moise Jr., M.D., Professor,
Department of Women's Health and Co-Director, Comprehensive Fetal
Care Center at Dell Medical School of the University of Texas at Austin and lead study
investigatorb. "For many patients, severe HDFN has a
poor prognosis, and the current standard of care carries with it a
high treatment burden, such as repeated IUTs and additional
in-utero procedures that require access to specialty care and carry
a risk to the life of the fetus. If approved, nipocalimab would be
the first non-surgical treatment for pregnancies at high risk of
HDFN."3
The multicenter, open-label, single-arm Phase 2 UNITY study
assessed intravenous nipocalimab from 14-35 weeks in pregnancies at
high risk for recurrent EOS HDFN.1 The primary
endpoint of the study is live birth at ≥32 weeks GA without IUT.
Study results showed the primary endpoint was achieved in 54
percent (7/13) of pregnancies versus the 10 percent historical
benchmark (95 percent CI, 25.1-80.8;
P<0.001).1 The NEJM manuscript includes
new data that compares the outcomes of qualifying
pregnanciesc and on-study (UNITY)
pregnancies.1 The comparison revealed that study
pregnancies had a higher proportion of live births (92 percent
versus 38 percent), fewer participants requiring IUTs (85 percent
versus 46 percent), a later median GA at first IUT (27 and 1/7
weeks versus 20 and 4/7 weeks) and a later median GA at delivery
(36 4/7 weeks versus 23 and 6/7
weeks).1 Additionally, among pregnant individuals
who joined the study, seven had a fetus that developed hydrops in
their most recent qualifying pregnancy, whereas no incidences of
hydrops occurred in the study pregnancies.1
In the UNITY study, the most frequently reported adverse events
were consistent with those common in pregnancy and
HDFN.1 Serious side effects were consistent with
HDFN or other pregnancy-related conditions including subchorionic
hematoma and premature separation of the placenta.1
Infections and illnesses in infants of mothers exposed to
nipocalimab were consistent with those typically observed in the
neonatal and infancy period.1 No maternal or
neonatal/infant deaths occurred in the study.1 One
pregnancy resulted in fetal demise related to a complication of an
IUT.1
The UNITY study demonstrated positive efficacy and safety
results which supports a favorable benefit risk profile for
nipocalimab.1 Thus, the UNITY study results support
further clinical development of nipocalimab for the treatment of
severe HDFN.1 The AZALEA Phase 3 pivotal study is
currently enrolling pregnant individuals at risk for severe HDFN
who have a history of severe HDFN in a prior pregnancy(ies) to
further assess the efficacy and safety of nipocalimab.4
In addition, Johnson & Johnson is conducting a Phase 3
study of nipocalimab in fetal and neonatal alloimmune
thrombocytopenia (FNAIT), which has been considered to be the
platelet counterpart of HDFN.5 FNAIT is an
alloimmune disorder of pregnancy that results when the pregnant
person's immune system attacks fetal or newborn platelets,
resulting in thrombocytopenia and risk of bleeding, which can be
life-threatening.6
"We are committed to developing non-surgical options that are
effective and have a proven safety profile for the treatment of
alloantibody-driven maternal-fetal diseases," said Katie Abouzahr, M.D., Vice President,
Autoantibody Diseases and Maternal-Fetal Immunology Disease Area
Leader, Johnson & Johnson Innovative Medicine. "The data
published in the NEJM underscore the potential of
nipocalimab to address the high unmet medical need in severe
HDFN, a serious, life-threatening and rare condition in
which no other therapies in clinical development exist."
Editor's Notes:
a. Alloimmunized: immune response to foreign antigens upon
exposure to genetically different cells or tissues
b. Dr. Kenneth Moise is a paid
consultant for Janssen. He has not been compensated for any media
work.
c. Most recent qualifying pregnancy: previous HDFN pregnancy
that made the participant eligible for the UNITY Phase 2 study
ABOUT THE UNITY STUDY
UNITY (NCT03842189) is a global, multicenter, non-blinded Phase
2 clinical study designed to evaluate the safety, efficacy,
pharmacokinetics and pharmacodynamics of nipocalimab for the
treatment of pregnant individuals at high risk for early-onset
severe (EOS)-HDFN.7 The study enrolled RhD (D) or Kell
(K) alloimmunized pregnant individuals with singleton pregnancies
at high risk for EOS-HDFN due to an obstetric history of severe
fetal anemia, fetal hydrops, or a stillbirth at ≤24 weeks
GA.1 The primary endpoint was live birth at or
after GA of 32 weeks, without a need for an intrauterine
transfusion (IUT) throughout the entire
pregnancy.1 Safety was monitored for 24 weeks
post-delivery for the 13 maternal individuals enrolled, and up to
96 weeks post-birth for infants. Participants received
once-weekly intravenous infusions.1 The study met
the primary endpoint, with 54 percent of pregnant participants who
received nipocalimab achieving a live birth at or after 32 weeks
GA, without the need for an IUT throughout their entire
pregnancy.1
ABOUT HDFN
Hemolytic disease of the fetus and newborn (HDFN) is a rare
disease (and in its severe form, ultra rare) that arises in
pregnancies with maternal-fetal incompatibility in certain red
blood cell types.8 Alloantibodies produced by the
maternal immune system against fetal red blood cells cross the
placenta during pregnancy and attack fetal red blood cells causing
fetal anemia or persist after birth in the neonate to cause
neonatal hyperbilirubinemia and anemia.2 The
symptoms of HDFN can range from mild jaundice, to neurotoxic
hyperbilirubinemia in the newborn, to life-threatening fetal anemia
requiring invasive intervention.9 The potential for
in utero onset at an increasingly earlier GA with increasing
risk of severe outcomes may occur with each incompatible pregnancy
due to pregnancy-related alloimmunization.10 Currently
no non-surgical interventions are approved for pregnancies at high
risk for severe HDFN.3 Pregnancies affected by
severe HDFN may necessitate repeated intrauterine transfusions
(IUTs), which are invasive, technically complex surgical procedures
performed by specialists at specialized medical centers, and these
procedures are associated with an increased rate of fetal mortality
and premature birth.11,12, 13 The most difficult to
treat cases of HDFN are early onset severe HDFN (EOS-HDFN) that
develops at ≤24 weeks gestational age (GA) and results in
significant fetal/neonatal morbidity and mortality. According
to the American Journal of Obstetrics and Gynecology, in the
U.S., it is estimated that up to 80 of every 100,000 pregnancies
are affected by HDFN each year.14
ABOUT NIPOCALIMAB
Nipocalimab is an investigational monoclonal antibody,
purposefully designed to bind with high affinity to block FcRn and
reduce levels of circulating immunoglobulin G (IgG) antibodies,
while preserving immune function without causing broad
immunosuppression. This includes autoantibodies and alloantibodies
that underlie multiple conditions across three key segments in the
autoantibody space including Rare Autoantibody diseases,
Maternal-Fetal diseases mediated by maternal alloantibodies and
Prevalent
Rheumatology.15,16,17,18,19,20,21,22,23 Blockade of
IgG binding to FcRn in the placenta is also believed to prevent
transplacental transfer of maternal alloantibodies to the
fetus.24,25
The U.S. Food and Drug Administration (FDA) and European
Medicines Agency (EMA) have granted several key designations to
nipocalimab including:
- Fast Track designation in hemolytic disease of the fetus and
newborn (HDFN) and warm autoimmune hemolytic anemia (wAIHA) in
July 2019, gMG in December 2021 and fetal neonatal alloimmune
thrombocytopenia (FNAIT) in March
2024
- Orphan drug status for wAIHA in December 2019, HDFN in June 2020, gMG in February
2021, chronic inflammatory demyelinating polyneuropathy CIDP
in October 2021 and FNAIT in
December 2023
- Breakthrough Therapy designation for HDFN by the FDA in
February 2024
- Orphan medicinal product designation for HDFN by the EMA in
October 2019
ABOUT JOHNSON & JOHNSON
At Johnson & Johnson, we believe health is
everything. Our strength in healthcare innovation empowers us to
build a world where complex diseases are prevented, treated, and
cured, where treatments are smarter and less invasive,
and solutions are personal. Through our expertise in Innovative
Medicine and MedTech, we are uniquely positioned to innovate across
the full spectrum of healthcare solutions today to deliver the
breakthroughs of tomorrow, and profoundly impact health for
humanity.
Learn more at https://www.jnj.com/ or at
www.janssen.com/johnson-johnson-innovative-medicine.
Follow us at @JanssenUS and @JNJInnovMed.
Janssen Research & Development, LLC and Janssen Biotech,
Inc. are Johnson & Johnson companies.
Cautions Concerning Forward-Looking Statements
This press release contains "forward-looking statements" as
defined in the Private Securities Litigation Reform Act of 1995
regarding product development and the potential
benefits and treatment impact of nipocalimab. The reader is
cautioned not to rely on these forward-looking statements. These
statements are based on current expectations of future events. If
underlying assumptions prove inaccurate or known or unknown risks
or uncertainties materialize, actual results could vary materially
from the expectations and projections of Janssen Research &
Development, LLC, Janssen Biotech, Inc. and/or Johnson
& Johnson. Risks and uncertainties include, but are not limited
to: challenges and uncertainties inherent in product research and
development, including the uncertainty of clinical success and of
obtaining regulatory approvals; uncertainty of commercial success;
manufacturing difficulties and delays; competition, including
technological advances, new products and patents attained by
competitors; challenges to patents; product efficacy or safety
concerns resulting in product recalls or regulatory action; changes
in behavior and spending patterns of purchasers of health care
products and services; changes to applicable laws and regulations,
including global health care reforms; and trends toward health care
cost containment. A further list and descriptions of these risks,
uncertainties and other factors can be found in Johnson &
Johnson's Annual Report on Form 10-K for the fiscal year ended
December 31, 2023, including in the
sections captioned "Cautionary Note Regarding Forward-Looking
Statements" and "Item 1A. Risk Factors," and in Johnson &
Johnson's subsequent Quarterly Reports on Form 10-Q and other
filings with the Securities and Exchange Commission. Copies of
these filings are available online at
www.sec.gov, www.jnj.com or on request
from Johnson & Johnson. None of Janssen Research &
Development, LLC, Janssen Biotech, Inc. nor Johnson & Johnson
undertakes to update any forward-looking statement as a result of
new information or future events or developments.
1 Kenneth J. Moise
Jr., et al. Nipocalimab in Early-onset Severe Hemolytic
Disease of the Fetus & Newborn. N Engl J Med. 2024; DOI:
10.1056/NEJMoa2314466.
2 National Library of Medicine. Hemolytic Diseases of
the Newborn. StatPearls Publishing. 2023 Jan. Available at:
https://www.ncbi.nlm.nih.gov/books/NBK557423/. Last accessed:
August 2024.
3 DeMoss, P., Asfour, M. and Hersey, K. Anti-K1
(Kell) antibody expressed in maternal breastmilk: A case report of
a neonate with multiple intrauterine transfusions and postnatal
exposure to Kell antibody in maternal breastmilk', Case reports in
pediatrics. 2017. Doi:10.1155/2017/6927813. Last accessed:
August 2024.
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Efficacy, Pharmacokinetics and Pharmacodynamics of M281
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Hemolytic Disease of the Fetus and Newborn (HDFN). Last accessed:
August 2024.
https://clinicaltrials.gov/ct2/show/NCT03842189.
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accessed: August 2024.
6 NORD. Fetal and Neonatal Alloimmune
Thrombocytopenia. Published online July
2022.
https://rarediseases.org/rare-diseases/fetal-and-neonatal-alloimmune-thrombocytopenia/.
Last accessed August 2024.
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Available at: https://clinicaltrials.gov/study/NCT03842189. Last
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8 Hemolytic disease of the newborn. Medline Plus.
Last accessed: August 2024.
https://medlineplus.gov/ency/article/001298.htm
9 Ree IMC, Smits-Wintjens VEHJ, van der Bom JG, et
al. Neonatal management and outcome in alloimmune hemolytic
disease, Expert Review of Hematology, 10:7, 607-616, doi:
10.1080/17474086.2017.1331124. Last accessed: August 2024.
10 Lobato G, Soncini CS. Relationship between
obstetric history and Rh(D) alloimmunization severity. Arch Gynecol
Obstet. 2008 Mar;277(3):245-8. Doi: 10.1007/s00404-007-0446-x. Last
accessed: August 2024.
11 Texas Children's Hospital. Intrauterine
Transfusion. Available
at: https://women.texaschildrens.org/program/texas-childrens-fetal-center/procedures-offered/intrauterine-transfusion.
Last accessed: August 2024.
12 de Winter DP, Kaminski A, et al. Hemolytic disease
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Doi: https://doi.org/10.1186/s12884-022-05329-z. Last accessed:
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13 Lindenburg IT, van Kamp IL, van Zwet EW,
Middeldorp JM, Klumper FJ, Oepkes D. Increased perinatal loss after
intrauterine transfusion for alloimmune anaemia before 20 weeks of
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Obstet. 2008 Mar;277(3):245-8. DOI: 10.1007/s00404-007-0446-x. Last
accessed: June 2024.
25 Roy S, Nanovskaya T, Patrikeeva S, et al. M281, an
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2019;220(5):498 e491-498 e499.
Media contact:
Bridget Kimmel
Mobile: (215)
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bkimmel@its.jnj.com
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