Hyaluronidase

OSAKA, Japan & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Takeda (TSE:4502/NYSE:TAK) today announced that the U.S. Food and Drug Administration (FDA) has granted 510(k) clearance for HyHubTM and HyHubTM Duo, devices for patients 17 years of age and older that allow HYQVIA® [Immune Globulin Infusion (Human), 10% with Recombinant Human Hyaluronidase] to be transferred from vials without using a needle in a home environment or clinical setting.2 The HYQVIA administration process consists of dual vial units (DVUs) including one vial of immunoglobulin (IG) and one vial of hyaluronidase. HyHub and HyHub Duo, which act as docking stations for these vials, were developed to simplify administration of HYQVIA by reducing the number of steps required to prepare the infusion of two DVUs or more.1 HYQVIA is a combination of IG and hyaluronidase for facilitated subcutaneous immunoglobulin (SCIg) infusion that is approved for treatment of adults and children two years of age and older with primary immunodeficiency (PI) and as maintenance therapy for adults with chronic inflammatory demyelinating polyneuropathy (CIDP) in the United States.2 Depending on the indication, HYQVIA can be infused up to once monthly (every two, three or four weeks). “This milestone exemplifies our dedication to advancing innovative solutions that can enhance the treatment administration experience for people who rely on infusions of facilitated immunoglobulin like HYQVIA,” said Kristina Allikmets, senior vice president and head of Research & Development for Takeda’s Plasma-Derived Therapies Business Unit. “We designed HyHub and HyHub Duo, Takeda’s first customized devices for use with a plasma-derived therapy, with input from patients and caregivers, demonstrating our focus on leveraging technology and deep insights to offer a patient-centric ecosystem of support throughout the treatment journey.” HyHub and HyHub Duo reduce the number of steps required to prepare the IG and hyaluronidase of the HYQVIA infusion by up to half compared to infusing with a pooling bag depending on the device and number of DVUs used.1* HyHub and HyHub Duo also reduce the ancillary supplies required to prepare the infusion and a dedicated carrier bag is available for convenience that enables room-to-room mobility.3 “For people living with primary immunodeficiency, innovative devices that can help simplify the administration process of their immunoglobulin treatment can be especially meaningful as many require lifelong treatment for their disease,” said Jorey Berry, president and chief executive officer of the Immune Deficiency Foundation. HyHub and HyHub Duo are intended for use only with HYQVIA and the devices will be available at no additional cost to patients. Takeda anticipates making HyHub and HyHub Duo available in the United States starting in the second half of fiscal year 2025. Takeda also submitted a CE Mark application for HyHub and HyHub Duo in the European Union during the first quarter of fiscal year 2025 and will evaluate making the device available in other markets in the future. * HyHub reduces the number of steps by approximately half for four DVUs. HyHub Duo reduces the number of steps by about one third for two DVUs. About HYQVIA® [Immune Globulin Infusion (Human), 10% with Recombinant Human Hyaluronidase] HYQVIA® is a liquid medicine containing Recombinant Human Hyaluronidase and immunoglobulins (Ig) and is approved in the United States to treat adults and children two years of age and older with primary immunodeficiency (PI), and as maintenance therapy to prevent relapse of neuromuscular disability and impairment in adult patients with CIDP. It is also approved by the European Medicines Agency (EMA) as a replacement therapy in adults, children and adolescents with PI and with secondary immunodeficiency (SID) who suffer from severe or recurrent infections, ineffective antimicrobial treatment, and either proven specific antibody failure (PSAF) or serum IgG level of <4 g/L. In addition, it is approved by the EMA as maintenance therapy in adults, children and adolescents (0-18 years) with CIDP after stabilization with intravenous immunoglobulin therapy (IVIG). HYQVIA is infused under the skin into the fatty subcutaneous tissue. HYQVIA contains IG collected from human plasma. IG are antibodies that maintain the body’s immune system. The hyaluronidase part of HYQVIA facilitates the dispersion and absorption of IG in the subcutaneous space between the skin and the muscle. HYQVIA is infused up to once a month (every two, three or four weeks for CIDP; every three or four weeks for PI). HyHub/HyHub Duo Important Information for Healthcare Providers Intended Use: HyHub/HyHub Duo are stand-alone, single-use, disposable vial access devices. Indications for Use: HyHub/HyHub Duo are indicated for patients 17 years of age and older to allow HYQVIA [Immune Globulin Infusion (Human), 10% with Recombinant Human Hyaluronidase] to be transferred from vials without using a needle, as prescribed, in a home environment or clinical setting. Contraindications: Do not use HyHub/HyHub Duo with a pooling bag. Do not connect HyHub/HyHub Duo to a syringe driver infusion pump. Selected Information for Patients: Patients should not use HyHub/HyHub Duo at home until receiving instructions and training from a healthcare provider. Patients should not exceed the maximum infusion volume per infusion site or infusion rate as indicated in the HYQVIA prescribing information. For safe and proper use of HyHub/HyHub Duo, please refer to the complete Instructions for Use included with the devices when they become available in the second half of FY2025. For information about HYQVIA, please see Prescribing Information for HYQVIA. INDICATIONS FOR HYQVIA HYQVIA is indicated for the treatment of primary immunodeficiency (PI) in adults and pediatric patients two years of age and older and for chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment in adults. HYQVIA is for subcutaneous use only. IMPORTANT SAFETY INFORMATION FOR HYQVIA WARNING: THROMBOSIS Contraindications History of anaphylactic or severe systemic hypersensitivity reactions to human IG IgA-deficient patients with antibodies to IgA and a history of hypersensitivity to human IG Known systemic hypersensitivity to hyaluronidase including Recombinant Human Hyaluronidase of HYQVIA Known systemic hypersensitivity to human albumin (in the hyaluronidase solution) Warnings and Precautions Hypersensitivity: Severe hypersensitivity reactions may occur, even in patients previously treated with IG products. If a hypersensitivity reaction occurs, discontinue infusion immediately and institute appropriate treatment. IgA-deficient patients with antibodies to IgA are at greater risk of developing potentially severe hypersensitivity reactions, including anaphylaxis. Thrombosis: Has been reported to occur following treatment with IG products, including HYQVIA and in the absence of known risk factors. In patients at risk, administer at the minimum dose and infusion rate practicable. Ensure adequate hydration before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. Immunogenicity of Recombinant Human Hyaluronidase (rHuPH20): Has been reported to occur following treatment with IG products, including HYQVIA and in the absence of known risk factors. In patients at risk, administer at the minimum dose and infusion rate practicable. Ensure adequate hydration before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. Aseptic Meningitis Syndrome: Has been reported to occur with use of IG, including HYQVIA. The syndrome usually begins within several hours to two days following IG treatment. Conduct a thorough neurological exam on patients exhibiting signs and symptoms, to rule out other causes of meningitis. Discontinuing IG treatment has resulted in remission within several days without sequelae. Hemolysis: HYQVIA contains blood group antibodies which may cause a positive direct antiglobulin reaction and hemolysis. Monitor patients for signs and symptoms of hemolysis and delayed hemolytic anemia and, if present, perform appropriate confirmatory lab testing. Renal Dysfunction/Failure: Acute renal dysfunction/failure, acute tubular necrosis, proximal tubular nephropathy, osmotic nephrosis, may occur with IG products, including HYQVIA. Ensure patients are not volume depleted prior to infusion. In patients at risk due to pre-existing renal insufficiency or predisposition to acute renal failure, administer HYQVIA at the minimum rate of infusion practicable. Assess renal function before initiation and throughout treatment, and consider lower, more frequent dosing. If renal function deteriorates, consider discontinuation. Spread of Localized Infection: Do not infuse HYQVIA into or around an infected area due to potential risk of spreading a localized infection. Transfusion-Related Acute Lung Injury: Non-cardiogenic pulmonary edema may occur with IV administered IG. Monitor patients for pulmonary adverse reactions. If suspected, perform appropriate tests for presence of anti-neutrophil and anti-HLA antibodies in both product and patient serum. Manage using oxygen therapy with adequate ventilatory support. Transmittable Infectious Agents: Because HYQVIA is made from human plasma, there is a risk of transmitting infectious agents (e.g. viruses, other pathogens). Interference with Lab Tests: False positive serological test results and certain assay readings, with the potential for misleading interpretation, may occur as the result of passively transferred antibodies. Adverse Reactions The most common adverse reactions observed in >5% of patients in the clinical trials were: Primary Immunodeficiency (PI): Local reactions, headache, antibody formation against rHuPH20, fatigue, nausea, pyrexia, and vomiting. Chronic Inflammatory Demyelinating Polyneuropathy (CIDP): Local reactions, headache, pyrexia, nausea, fatigue, erythema, pruritus, increased lipase, abdominal pain, back pain, and pain in extremity. Drug Interactions Passive transfer of antibodies may transiently interfere with the immune responses to live attenuated virus vaccines (e.g., measles, mumps, rubella, and varicella). Use in Specific Populations Pregnancy: Limited human data are available on the use of HYQVIA during pregnancy. The effects of antibodies to the Recombinant Human Hyaluronidase on the human embryo or fetal development are unknown. It is not known whether HYQVIA can cause fetal harm when administered to a pregnant woman or if it can affect reproductive capacity. HYQVIA should be given to a pregnant woman only if clearly needed. Please click for Full Prescribing Information. For European Union Summary of Product Characteristics, please visit: https://www.ema.europa.eu/en/medicines/human/EPAR/hyqvia About Takeda Takeda is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to discover and deliver life-transforming treatments, guided by our commitment to patients, our people and the planet. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Rare Genetics and Hematology, Neuroscience, and Gastroenterology (GI). We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people’s lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. 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Takeda does not undertake to update any of the forward-looking statements contained in this press release or any other forward-looking statements it may make, except as required by law or stock exchange rule. Past performance is not an indicator of future results and the results or statements of Takeda in this press release may not be indicative of, and are not an estimate, forecast, guarantee or projection of Takeda’s future results. Medical information This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development. References 1 Data on File. Takeda Pharmaceuticals. 2 HYQVIA [Immune Globulin Infusion (Human), 10% with Recombinant Human Hyaluronidase] U.S. Prescribing Information. 3 Data on File. Takeda Pharmaceuticals.

More than half of patients maintained minimal residual disease (MRD) negativity (10-5) with DARZALEX FASPRO® for 24 months or longer in the Phase 3 PERSEUS study Data from Phase 3 CEPHEUS study show 60 percent overall MRD negativity (10−5) and improved PFS with DARZALEX FASPRO® in transplant-ineligible newly diagnosed patients CHICAGO, June 3, 2025 /PRNewswire/ -- Johnson & Johnson (NYSE: JNJ) today announced data from two studies highlighting that a DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)-based quadruplet regimen demonstrated deep and sustained minimal residual disease (MRD) negativity rates, and improved long-term progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM), regardless of transplant status.1,2,3 Findings were highlighted as oral presentations of an analysis of sustained MRD in transplant-eligible patients from the Phase 3 PERSEUS study (Abstract #7501) and a subgroup analysis of transplant-ineligible patients in the Phase 3 CEPHEUS study (Abstract #7516) at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. New analysis from the Phase 3 PERSEUS study shows the addition of DARZALEX FASPRO® to bortezomib, lenalidomide and dexamethasone (D-VRd), followed by an investigational maintenance regimen of DARZALEX FASPRO® with lenalidomide (D-R), led to improved and deepened rates of overall and sustained MRD negativity (10-5), defined as no cancer cells detected within 100,000 bone marrow cells) for at least 24 months, compared to VRd induction and consolidation with R maintenance. More than half of patients who received the DARZALEX FASPRO®-based regimen achieved sustained MRD negativity for 24 or more months and more than two-thirds of patients achieved sustained MRD-negativity at 12-months, showing 95.3 percent PFS at 48-months (95 percent confidence interval [CI], 0.3-2.3)—reinforcing the ability of DARZALEX FASPRO® to delay disease progression or death.1 "The data show that D-VRd followed by an investigational D-R maintenance regimen is a highly effective treatment option for transplant-eligible patients with newly diagnosed multiple myeloma," said Philippe Moreau*, M.D., head of the Hematology Department, University Hospital Hôtel-Dieu, Nantes, France and presenting author. "The depth and durability of MRD negativity observed—paired with unprecedented progression-free survival at four years—underscore the long-term benefit the DARZALEX FASPRO-based regimen can offer patients early in their treatment journey." At a median follow-up of 47.5 months, 24-month sustained MRD negativity rates at the 10⁻⁵ sensitivity threshold were more than double with D-VRd followed by investigational D-R maintenance (55.8 percent), compared to VRd followed by R maintenance (22.6 percent) (odds ratio [OR]=4.36; 95 percent CI, 3.15-6.05; P<0.0001). Similarly, MRD negativity at 12 months was higher with D-VRd and D-R maintenance at 64.8 percent compared to VRd and R maintenance (29.7 percent) (OR=4.42, 95 percent CI, 3.22-6.08, P<0.0001).1 Additional data from Phase 3 CEPHEUS study explore the benefits of DARZALEX FASPRO® in transplant-ineligible patients across cytogenetic risk status The post-hoc analysis of the Phase 3 CEPHEUS study focused exclusively on transplant-ineligible patients, reinforcing that adding DARZALEX FASPRO® to VRd significantly deepens response and prolongs PFS compared to VRd alone, even in patients who are older and considered frail by the Myeloma Geriatric Assessment score. At a median follow-up of 58.7 months, patients receiving D-VRd achieved markedly higher overall MRD negativity rates at the 10⁻⁵ sensitivity threshold with 60.4 percent versus 39.3 percent with VRd (OR 2.37; 95 percent CI, 1.47–3.80; P=0.0004). Furthermore, treatment with D-VRd resulted in high MRD-negativity rates at the 10⁻⁶ threshold (no cancer cells detected within 1,000,000 bone marrow cells) with 45.8 percent compared to 26.9 percent with VRd (OR 2.28; 95 percent CI, 1.40–3.73; P=0.0010). These deeper responses translated into improved long-term outcomes, with 69 percent of patients remaining progression free at 54-months when treated with D-VRd versus 48.0 percent with VRd (hazard ratio [HR] 0.51; 95 percent CI, 0.35–0.74). Overall survival (OS) numerically favored D-VRd (HR 0.66; 95 percent CI, 0.42–1.03), with an even greater benefit observed after censoring for COVID-19-related deaths (HR 0.55; 95 percent CI, 0.34–0.90).2 Additional data presented at ASCO included a subgroup analysis of the CEPHEUS trial for both transplant-ineligible and deferred NDMM patients who were considered high-risk for cytogenetic abnormalities (Abstract #7529). At a median follow-up of 58.7 months, overall MRD negativity rate was improved for patients with standard risk in D-VRd versus VRd. Rates by treatment arm in patients at high risk were comparable.3 "Across multiple studies, the growing body of data on DARZALEX-based regimens indicates impressive, deep responses and meaningful progression-free survival in patients with newly diagnosed multiple myeloma, including high risk," Jordan Schecter, MD, Vice President, Disease Area Leader, Multiple Myeloma, Johnson & Johnson Innovative Medicine. "These consistent results across patient populations, regardless of transplant eligibility, reinforce the role of DARZALEX FASPRO as a cornerstone of frontline therapy." In the PERSEUS and CEPHEUS studies, the safety profiles were consistent with the known safety profile for DARZALEX FASPRO®. About the PERSEUS Study The PERSEUS study is being conducted in collaboration with the European Myeloma Network as the sponsor. PERSEUS is an ongoing, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd during induction and consolidation versus VRd during induction and consolidation in patients with NDMM eligible for ASCT. Following consolidation, patients received an investigational treatment regimen for maintenance that included DARZALEX FASPRO® in combination with lenalidomide or lenalidomide alone. The trial was not designed to isolate the effect of DARZALEX FASPRO® in the maintenance phase of treatment. The efficacy of DARZALEX FASPRO® in combination with lenalidomide for maintenance has not been established. The primary endpoint is PFS, and secondary endpoints include overall CR or better rate, and overall MRD-negativity (in patients with CR or better). The median age is 61.0 (range, 32-70) years for patients in the D-VRd arm and 59.0 (range, 31-70) years for patients in the VRd arm.2 The study is being conducted in 14 countries in Europe and Australia. About the CEPHEUS Study CEPHEUS (NCT03652064) is an ongoing, multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd versus VRd in patients with newly diagnosed multiple myeloma who are transplant-ineligible or for whom transplant is not intended as initial therapy. Primary endpoint is overall MRD negativity rate at 10-5 sensitivity threshold. Secondary endpoints include CR or better rates, PFS, sustained MRD negativity rates for ≥12 months, MRD-negative rate at one year, overall response rates, time to and duration of response, PFS on next line of therapy, overall survival and safety. The trial has enrolled 396 patients in 13 countries. About Multiple Myeloma Multiple myeloma (MM) is a blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.4 In multiple myeloma, these malignant plasma cells proliferate and replace normal cells in the bone marrow.5 Multiple myeloma is the second most common blood cancer worldwide and remains an incurable disease.6 In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 will die from the disease.7 People with multiple myeloma have a 5-year survival rate of 59.8 percent. While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.8,9 About DARZALEX FASPRO ® and DARZALEX ® DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for nine indications in MM, four of which are for frontline treatment in newly diagnosed patients who are transplant-eligible or ineligible.3,6 It is the only subcutaneous CD38-directed antibody approved to treat patients with MM. DARZALEX FASPRO® is co-formulated with recombinant human hyaluronidase PH20, Halozyme's ENHANZE® drug delivery technology. DARZALEX® (daratumumab) received U.S. FDA approval in November 2015 and is approved in eight indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant-eligible and ineligible.9 DARZALEX® is the first CD38-directed antibody approved to treat MM.9 DARZALEX®-based regimens have been used in the treatment of more than 618,000 patients worldwide. In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab.  For more information, visit .  DARZALEX FASPRO ® INDICATIONS AND IMPORTANT SAFETY INFORMATION    INDICATIONS  DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with MM:  In combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in newly diagnosed patients who are eligible for autologous stem cell transplant In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory MM who have received at least one prior therapy In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor (PI) In combination with carfilzomib and dexamethasone in patients with relapsed or refractory MM who have received one to three prior lines of therapy In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy As monotherapy in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double refractory to a PI and an immunomodulatory agent IMPORTANT SAFETY INFORMATION   CONTRAINDICATIONS     DARZALEX FASPRO® is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation.     WARNINGS AND PRECAUTIONS     Hypersensitivity and Other Administration Reactions     Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO®. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO®.    Systemic Reactions     In a pooled safety population of 1249 patients with MM (N=1056) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO® as monotherapy or in combination, 7 percent of patients experienced a systemic administration-related reaction (Grade 2: 3.2 percent, Grade 3: 0.7 percent, Grade 4: 0.1 percent). Systemic administration-related reactions occurred in 7 of patients with the first injection, 0.2 percent with the second injection, and cumulatively 1 percent with subsequent injections. The median time to onset was 2.9 hours (range: 5 minutes to 3.5 days). Of the 165 systemic administration-related reactions that occurred in 93 patients, 144 (87 percent) occurred on the day of DARZALEX FASPRO® administration. Delayed systemic administration-related reactions have occurred in 1 percent of the patients.  Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision.     Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO®. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO® depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.     Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX FASPRO® and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO®.     Local Reactions     In this pooled safety population, injection-site reactions occurred in 7 percent of patients, including Grade 2 reactions in 0.8 percent. The most frequent (>1 percent) injection-site reaction was injection-site erythema. These local reactions occurred a median of 5 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO®. Monitor for local reactions and consider symptomatic management.     Neutropenia     Daratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO® until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO®, higher rates of Grade 3-4 neutropenia were observed.     Thrombocytopenia     Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Consider withholding DARZALEX FASPRO® until recovery of platelets.     Embryo-Fetal Toxicity     Based on the mechanism of action, DARZALEX FASPRO® can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO® and for 3 months after the last dose.     The combination of DARZALEX FASPRO® with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy.     Interference With Serological Testing     Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient's serum. The determination of a patient's ABO and Rh blood type are not impacted.     Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO®. Type and screen patients prior to starting DARZALEX FASPRO®.     Interference With Determination of Complete Response     Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO®-treated patients with IgG kappa myeloma protein.     ADVERSE REACTIONS     In MM, the most common adverse reaction (≥20 percent) with DARZALEX FASPRO® monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20 percent for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, headache, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, upper respiratory tract infection, peripheral sensory neuropathy, constipation, pneumonia, and peripheral edema.     The most common hematology laboratory abnormalities (≥40 percent) with DARZALEX FASPRO® are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.     Please click here to see the full Prescribing Information for DARZALEX FASPRO ® .     DARZALEX ® INDICATIONS AND IMPORTANT SAFETY INFORMATION INDICATIONS   DARZALEX ® (daratumumab) is indicated for the treatment of adult patients with MM:   In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory MM who have received at least one prior therapy In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor In combination with carfilzomib and dexamethasone in patients with relapsed or refractory MM who have received one to three prior lines of therapy In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent CONTRAINDICATIONS DARZALEX® is contraindicated in patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any of the components of the formulation.   WARNINGS AND PRECAUTIONS   Infusion-Related Reactions   DARZALEX® can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37 percent of patients with the Week 1 (16 mg/kg) infusion, 2 percent with the Week 2 infusion, and cumulatively 6 percent with subsequent infusions. Less than 1 percent of patients had a Grade 3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX®. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension and blurred vision. When DARZALEX® dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX®, the incidence of infusion-related reactions was 11 percent for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX® following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1 percent) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days, ie, 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42 percent, with 36 percent of patients experiencing infusion-related reactions on Day 1 of Week 1, 4 percent on Day 2 of Week 1, and 8 percent with subsequent infusions. Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion. To reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX® infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease. Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX® infusion. If ocular symptoms occur, interrupt DARZALEX® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX®. Interference With Serological Testing   Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient's serum. The determination of a patient's ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX®. Type and screen patients prior to starting DARZALEX®. Neutropenia and Thrombocytopenia   DARZALEX® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX® until recovery of neutrophils or for recovery of platelets. Interference With Determination of Complete Response   Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein. Embryo-Fetal Toxicity   Based on the mechanism of action, DARZALEX® can cause fetal harm when administered to a pregnant woman. DARZALEX® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX® and for 3 months after the last dose. The combination of DARZALEX® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy. ADVERSE REACTIONS   The most frequently reported adverse reactions (incidence ≥20 percent) were: upper respiratory infection, neutropenia, infusion related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (≥40 percent) with DARZALEX® are: neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia. Please click here to see the full Prescribing Information. 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 or at . Follow us at @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc., and Janssen Global Services, LLC 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 DARZALEX FASPRO®. 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 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 most recent Annual Report on Form 10-K, 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 , , or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments. Source: Johnson & Johnson * Philippe Moreau, M.D., head of the Hematology Department, University Hospital Hôtel-Dieu, Nantes, France, has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work. 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