KING OF PRUSSIA, Pa. — 09 November 2017
Global biotherapeutics leader CSL Behring announced that results were published in The Lancet Neurology from its PATH study (Polyneuropathy And Treatment with Hizentra®), a pivotal Phase III study evaluating the safety, efficacy and tolerability of Hizentra (Immune Globulin Subcutaneous [Human] 20% liquid) compared to placebo as maintenance therapy in patients with chronic inflammatory demyelinating polyneuropathy (CIDP), a rare autoimmune disorder that affects the peripheral nerves.
The study met its primary efficacy endpoint, demonstrating that 39 percent of patients on low-dose Hizentra (0.2 g/kg weekly) and 33 percent of patients on high-dose Hizentra (0.4 g/kg weekly) experienced a CIDP relapse or withdrew from the study over a 24-week treatment period (p values of 0.007 and 0.001 respectively, as measured by one-sided Fisher’s exact tests) compared with 63 percent of patients on placebo. Additionally, the study showed that 81 percent of patients treated with the high dose and 67 percent treated with the low dose remained relapse-free for up to 24 weeks. CIDP relapse was defined as a deterioration (i.e., increase) by at least one point in the total adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) score (range 0 [healthy] to 10 [unable to make any purposeful movements with arms or legs]) at any subcutaneous treatment period compared with baseline.
“Subcutaneous administration of immunoglobulin has gained popularity as an alternative route of administration but has never been rigorously examined for the treatment of CIDP until the PATH study,” said Prof. Dr. Ivo N. van Schaik, principal investigator, lead author of The Lancet Neurology publication, and professor of neurology at the University of Amsterdam's Faculty of Medicine (AMC-UvA). “In this groundbreaking study, Hizentra maintained stable disease and prevented relapse, suggesting that subcutaneous immunoglobulin may be used as an alternative maintenance therapy to intravenous immunoglobulin in CIDP patients.”
Both doses of Hizentra were safe and well tolerated. Adverse events occurred in 37 percent of the placebo group, 58 percent of the low-dose Hizentra group, and 52 percent of the high-dose Hizentra group. Most adverse events consisted of local reactions at the infusion site, which occurred more frequently in Hizentra-treated patients (19 percent of low-dose and 29 percent of high-dose patients) than in the placebo group (7 percent). All local reactions were either mild (95 percent) or moderate (5 percent) and none led to discontinuation. Of 11 serious adverse events reported, only one was assessed to be casually related, which led to treatment discontinuation.
Hizentra, a subcutaneously administered immunoglobulin (SCIG), is currently approved in 51 countries for the treatment of certain immune deficiencies. Based on the PATH study data, CSL Behring submitted applications to regulatory authorities in the United States and European Union, among other countries, for a CIDP indication.
“CSL Behring is committed to advancing innovative medical research to unlock the promise of immunoglobulins for the treatment of patients with disabling neurologic conditions, including CIDP. The PATH study underscores this commitment,” said Dr. Andrew Cuthbertson, Chief Scientific Officer and R&D director, CSL Limited. “If Hizentra is approved as a maintenance treatment for CIDP by regulatory authorities, we will be able to offer patients a flexible treatment option that allows them the freedom to self-administer immunoglobulin at a convenient place and time.”
About CIDP
In CIDP, a rare autoimmune disorder that affects the peripheral nerves (those outside the brain and spinal cord), the myelin sheath, the protective covering of the nerves, is damaged. This may result in numbness or tingling, muscle weakness, fatigue and other symptoms. CIDP effects can worsen over time, leading to significant activity limitations and a decreased quality of life. CIDP can occur at any age and is more common in men than in women. Approximately 30 percent of CIDP patients will progress to wheelchair dependence if not treated. In the U.S., it is estimated that the incidence of CIDP is up to two patients per 100,000 people each year,i with a prevalence of 40,000 people affected.ii
About Hizentra®
Hizentra (Immune Globulin Subcutaneous [Human]), the first 20 percent SCIG developed for subcutaneous use, is registered in over 51 countries and approved to treat certain immune deficiencies. Hizentra, the world's most prescribed SCIG, has a proven track record of safety, efficacy and tolerability and has over 4.8 million exposures worldwide since 2010.
For country-specific indication information, visit:
Australia: http://www.csl.com.au/productfinder/hizentraau
Brazil: http://www.anvisa.gov.br/datavisa/fila_bula/frmVisualizarBula.asp?pNuTransacao=18366392016&pIdAnexo=3535349
Canada: http://labeling.cslbehring.ca/PM/CA/Hizentra/EN/Hizentra-Product-Monograph.pdf
Europe: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002127/human_med_001440.jsp&mid=WC0b01ac058001d124
Japan: http://www.pmda.go.jp/PmdaSearch/iyakuDetail/100806_6343439A1024_1_04#CONTRAINDICATIONS
Switzerland: https://compendium.ch/home/de?nocookie=true (German) or https://compendium.ch/mpro/mnr/22484/html/fr (French)
United States: https://www.hizentra.com/prescribing-information
Important Safety Information for the US
Immune Globulin Subcutaneous (Human), Hizentra®, is indicated as replacement therapy for patients with primary humoral immunodeficiency (PI), age 2 and older. This includes but is not limited to the humoral immune defect in congenital agammaglobulinemia, common variable immunodeficiency, X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.
WARNING:THROMBOSIS
Thrombosis may occur with immune globulin products, including Hizentra. Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling vascular catheters, hyperviscosity, and cardiovascular risk factors.
For patients at risk of thrombosis, administer Hizentra at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. See full prescribing information for complete boxed warning.
Hizentra is contraindicated in patients with a history of anaphylactic or severe systemic reaction to human immune globulin preparations or components of Hizentra, such as polysorbate 80. Because it contains the stabilizer L-proline, Hizentra is contraindicated in patients with hyperprolinemia. Hizentra is also contraindicated in patients with immunoglobulin A deficiency who have antibodies against IgA and a history of hypersensitivity.
Hizentra should be administered subcutaneously only. Do not administer intravenously.
IgA-deficient patients with anti-IgA antibodies may be at greater risk of developing potentially severe hypersensitivity and anaphylactic reactions with administration of Hizentra. If hypersensitivity occurs or anaphylactic reactions are suspected, discontinue administration immediately and treat as medically appropriate.
Monitor patients for aseptic meningitis syndrome (AMS), which has been reported with SCIg. In patients at risk of acute renal failure, monitor renal function, including blood urea nitrogen, serum creatinine and urine output. Also monitor patients for clinical signs of hemolysis or transfusion-related acute lung injury (TRALI).
Hizentra is derived from human plasma. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be completely eliminated.
The most common adverse reactions (observed in 5% or more of study subjects receiving Hizentra) were local reactions (ie, swelling, redness, heat, pain, and itching at the injection site), headache, diarrhea, fatigue, back pain, nausea, extremity pain, cough, rash, pruritus, vomiting, upper abdominal pain, migraine and pain.
Ig administration can transiently impair the efficacy of live attenuated virus vaccines, such as measles, mumps and rubella. It can also lead to misinterpretation of serologic testing.
Please see full prescribing information for Hizentra, including boxed warning and the patient product information.
About CSL Behring
CSL Behring is a global biotherapeutics leader driven by its promise to save lives. Focused on serving patients’ needs by using the latest technologies, we develop and deliver innovative therapies that are used to treat coagulation disorders, primary immune deficiencies, hereditary angioedema, inherited respiratory disease, and neurological disorders. The company's products are also used in cardiac surgery, organ transplantation, burn treatment and to prevent hemolytic disease of the newborn.
CSL Behring operates one of the world's largest plasma collection networks, CSL Plasma. The parent company, CSL Limited (ASX:CSL), headquartered in Melbourne, Australia, employs nearly 20,000 people, delivering its life-saving therapies to people in more than 60 countries. For more information visit www.CSLBehring.com and follow us on www.Twitter.com/CSLBehring.
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i Laughlin R.S. et al. Incidence and prevalence of CIDP and the association of diabetes mellitus. Neurology. 7;73(1):39-45.
ii American Association of Neuromuscular & Electrodiagnostic Medicine (2017). Chronic Inflammatory Demyelinating Polyneuropathy. http://www.aanem.org/Patients/Disorders/Chronic-Inflammatory-Demyelinating-Polyneuropathy. Accessed October 2017.