BEERSE, BELGIUM, (8 August 2024) – Janssen-Cilag International NV, a Johnson & Johnson company today announced that the results from the Phase 2 open-label UNITY clinical study of nipocalimab for the treatment of alloimmuniseda pregnant individuals at risk of early-onset severe (EOS) HDFN have been published in The New England Journal of Medicine (NEJM). 1 The UNITY study met its primary endpoint, with 54 percent (n=7/13) of individuals receiving nipocalimab achieving a live birth at or after 32 weeks gestational age (GA) without the need for intrauterine transfusion (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 type of a pregnant individual and the developing foetus are incompatible, potentially causing life-threatening anaemia in the foetus or infant. 2,3 These results showed that nipocalimab delayed or prevented severe foetal anaemia requiring treatment prenatally, and reduced the need for IUTs in pregnancies at high risk for recurrent EOS-HDFN. 1
“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 foetus. If approved, nipocalimab would be the first non-surgical treatment for pregnancies at high risk of HDFN.”
The multicentre, open-label, single-arm Phase 2 UNITY clinical study assessed intravenous nipocalimab from 14-35 GA weeks in pregnancies at high risk for recurrent EOS-HDFN.1 The primary endpoint of the study was a live birth at or after ≥32 weeks GA without IUT.1 Study results showed the primary endpoint was achieved in 54 percent (n=7/13) of pregnancies versus the 10 percent historical benchmarkc (95 percent confidence interval [CI], 25.1-80.8; p<0.001).1 The NEJM manuscript includes new data that compare the outcomes of qualifying pregnanciesd and on-study (UNITY) pregnancies.1 The comparison revealed that on-study pregnancies, respectively, had a higher proportion of live births (92 percent [n=12/13] versus 38 percent [n=5/13]), with fewer participants requiring IUTs (46 percent [n=6/13] versus 85 percent [n=11/13]), 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 and 4/7 weeks versus 23 and 6/7 weeks).1 Additionally, during their qualifying pregnancy, seven previously had a foetus that developed hydropse, whereas no incidences of hydrops occurred in the on-study pregnancies. 1
In the UNITY study, the most frequently reported adverse events (AEs) were consistent with those common in pregnancy and HDFN. Serious AEs (SAEs) occurred in 38 percent (n=5/13) of maternal participants, while 46 percent (n=6/13) experienced severe AEs (grade ≥3).1 Among neonatal/infant participants, SAEs and severe AEs were reported in 42 percent (n=5/12) and 33 percent (n=4/12), respectively.1 Serious side effects were consistent with HDFN or other pregnancy-related conditions including subchorionic haematoma 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. One pregnancy resulted in foetal demise related to a complication of an IUT.1
The UNITY study demonstrated positive efficacy and safety results which supports an acceptable benefit risk profile for nipocalimab in the management of HDFN. 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 who have a history of severe HDFN in (a) prior pregnancy(ies) to further assess the efficacy and safety of nipocalimab. 2 In addition, Johnson & Johnson is conducting a Phase 3 study of nipocalimab in foetal and neonatal alloimmune thrombocytopenia (FNAIT), which has been considered to be the counterpart of HDFN with a target on platelets rather than RBC.4 FNAIT is an alloimmune disorder of pregnancy that results when the pregnant person’s immune system attacks foetal or newborn platelets, resulting in thrombocytopenia and risk of bleeding, which can be life-threatening to the infant.5
“Despite the progress made in prenatal and neonatal care, there remains a significant unmet need for people whose pregnancies are affected by HDFN, many of whom experience an invasive treatment burden,” said Ludovic de Beaucoudrey, Ph.D., Senior Director, Therapeutic Area Lead, Immunology, Janssen-Cilag Limited, a company of Johnson & Johnson. “We are focused on identifying innovative healthcare solutions for people who endure this devasting disease, and the publication of the UNITY Phase 2 data in the NEJM represents the latest milestone in our efforts to make meaningful strides in exploring the potential of nipocalimab for this community.”
“We are committed to developing, non-surgical options that are effective for the treatment of alloantibody-driven maternalfoetal 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 there are no other therapies in clinical development.”
Editor’s Notes:
a. Alloimmunised: immune response to foreign antigens upon exposure to genetically different cells or tissues.
b. Dr. Kenneth Moise is a paid consultant for Janssen-Cilag International NV. He has not been compensated for any media work.
c. Historical reference point used in this study is based on data from published literature (n=51); and academic research centres with expertise in managing EOS-HDFN, including the Fetal Center at Children’s Memorial Hermann Hospital in Houston, Texas, U.S. (n=2); The Department of Maternal Fetal Medicine at Ohio State University in Columbus, Ohio, U.S. (n=4); and The University of Toronto Fetal Medicine programme at Mount Sinai Hospital in Toronto, Canada (n=12). 6,7,8,9 Across these 69 cases, all patients with prior EOS-HDFN pregnancies required an IUT in subsequent at-risk pregnancies. A conservative benchmark of 10 percent of patients not requiring an IUT was chosen to account for uncertainties in the accuracy and representation of the underlying data.6
d. Most recent qualifying pregnancy: previous HDFN pregnancy that made the participant eligible for the Phase 2 UNITY study.
e. Foetal hydrops: a condition in which large amounts of fluid build-up in a baby’s tissues and organs, causing extensive swelling (oedema), and can be life-threatening.10 About half of unborn babies with hydrops do not survive.10 Foetal hydrops is a complication of HDFN, occurring when the mother’s immune system causes a baby’s red blood cells to break down.10
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ABOUT THE UNITY STUDY
UNITY (NCT03842189) is a global, multicentre, 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.11 The study enrolled RhD or Kell alloimmunised pregnant individuals with singleton pregnancies at high risk for EOS-HDFN due to an obstetric history of severe foetal anaemia, foetal hydrops, or a stillbirth at ≤24 weeks GA.1 The primary endpoint was a live birth at or after GA of 32 weeks, without a need for an 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
ABOUT HDFN
Haemolytic disease of the foetus and newborn (HDFN) is a rare disease (and in its severe form, ultra rare) that arises in pregnancies with maternal-foetal incompatibility in certain red blood cell types.3 Alloantibodies produced by the maternal immune system against foetal red blood cells cross the placenta during pregnancy and attack foetal red blood cells causing foetal anemia or persist after birth in the neonate to cause neonatal hyperbilirubinaemia and anaemia.3 The symptoms of HDFN can range from mild jaundice, to neurotoxic hyperbilirubinaemia in the newborn, to life-threatening foetal anaemia requiring invasive intervention.12 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 further alloimmunisation.13 Currently there are no non-surgical interventions approved for pregnancies at high risk for severe HDFN.14 Pregnancies affected by severe HDFN may necessitate repeated intrauterine transfusions (IUTs), which are invasive, technically complex surgical procedures performed by specialists at specialised medical centres, and these procedures are associated with an increased rate of foetal mortality and premature birth.15,16,17 The most difficult to treat cases of HDFN are early onset severe HDFN (EOS-HDFN) that develops at ≤24 weeks GA and results in significant foetal/neonatal morbidity and mortality.18 According to the EMA, in the European Union, it is estimated that the number of patients at risk of HDFN is approximately 3.6 people in 10,000.14
ABOUT NIPOCALIMAB
Nipocalimab is an investigational high-affinity, fully human, aglycosylated, effectorless monoclonal antibody, purposefully designed to bind with high affinity to block the neonatal Fc receptor (FcRn) and reduce levels of circulating immunoglobulin G (IgG) antibodies, including autoantibodies and alloantibodies that underlie multiple conditions19 across three key segments in the autoantibody space: Rare Autoantibody diseases (e.g., generalised myasthenia gravis in adults and children, chronic inflammatory demyelinating polyneuropathy (CIDP), warm autoimmune haemolytic anaemia (wAIHA), and idiopathic inflammatory myopathies), Maternal Foetal diseases mediated by maternal alloantibodies (e.g., haemolytic disease of the foetus and newborn (HDFN) and foetal and neonatal alloimmune thrombocytopaenia (FNAIT)), and Prevalent Rheumatology (e.g., rheumatoid arthritis, Sjögren’s disease, and systemic lupus erythematosus).20,21,22,23,24,25,26,27,28,29
The U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) have granted several key designations to nipocalimab including:
- Orphan medicinal product designation for HDFN by the EMA in October 2019
- U.S. FDA Fast Track designation in HDFN and wAIHA in July 2019, gMG in December 2021 and FNAIT in March 2024
- U.S. FDA Orphan drug status for wAIHA in December 2019, HDFN in June 2020, gMG in February 2021, CIDP in October 2021 and FNAIT in December 2023
- U.S. FDA Breakthrough Therapy designation for HDFN in February 2024
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 www.janssen.com/emea. Follow us at www.linkedin.com/jnj-innovative-medicine-emea. Janssen-Cilag International NV and Janssen-Cilag Limited are both 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-Cilag International NV, Janssen-Cilag Limited 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-Cilag International NV, Janssen-Cilag Limited, nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.
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July 2024