Transfusion-Related Acute Lung Injury

4Q 2023 Total Revenue of $73.9 Million; FY 2023 Total Revenue of $258.2 Million 4Q 2023 Adjusted EBITDA(1) of $18.6 Million; FY 2023 Adjusted EBITDA of $40.3 Million 4Q 2023 Adjusted Net Income(2) of $8.5 Million; FY 2023 Adjusted Net Income of $0.7 Million FY 2024 and 2025 Total Revenue Guidance Increased to More Than $330 Million and $380 Million, Respectively FY 2024 Net Income Guidance Increased to More Than $65 Million and Adjusted EBITDA Guidance Increased to More Than $90 Million FY 2025 Net Income Guidance Increased to More than $115 Million and Adjusted EBITDA Guidance Increased to More Than $140 Million Innovative Growth Opportunities Targeting Manufacturing and New Pipeline Hyperimmune Globulin to Advance During 2024 Conference Call Scheduled for Today at 4:30 p.m. ET RAMSEY, N.J. and BOCA RATON, Fla., Feb. 28, 2024 (GLOBE NEWSWIRE) -- ADMA Biologics, Inc. (Nasdaq: ADMA) (“ADMA” or the “Company”), an end-to-end commercial biopharmaceutical company dedicated to manufacturing, marketing and developing specialty biologics, today announced its fourth quarter and full year 2023 financial results and provided a business update. “We are pleased with our 2023 performance, which marked first-time positive adjusted net income on a full year basis. This is a testament to the exponential revenue growth of our commercial specialty biologics product portfolio and effective fiscal and operational management. As ADMA’s forward-looking business trends gain momentum, we're revising financial guidance upwards for both 2024 and 2025, increasing top and bottom-line projections,” said Adam Grossman, President and Chief Executive Officer of ADMA. “We believe our growing commercial success will be sustained by the recent and continuous expansion of ASCENIV utilization. We believe our unwavering focus on the immune deficient patient segment has allowed ADMA to establish itself as a premier provider of specialty biologics. We are confident that there is significant growth for ASCENIV within its addressable market, further penetrating the treatment setting comprised of immune deficient patients grappling with complex comorbidities.” Mr. Grossman continued, “In conjunction with the ongoing expansion of our commercial product portfolio, we look forward to advancing new growth initiatives, including innovations to ADMA’s manufacturing processes and potential yield enhancement, as well as progress with our preclinical S.pneumonia pipeline program. Based upon current market factors, we anticipate 2024 being defined by top-tier revenue and earnings growth, cash generation, and the further de-risking of growth initiatives which, if successful, we believe have the potential to significantly impact ADMA's peak revenue and earnings targets. We believe our proven internal R&D capabilities, broad intellectual property estate and successful establishment of our innovative commercial model position the Company for enduring success in the future.” (1) Adjusted EBITDA is a non-GAAP financial measure. For a reconciliation of Adjusted EBITDA to the most comparable GAAP measure, please see the reconciliation included in the financial tables. (2) Adjusted net income is a non-GAAP financial measure. For reconciliation of Adjusted net income to the most comparable GAAP measure, please see the reconciliation included in the financial tables. 2024-2025 Financial Guidance: FY 2024 and 2025 total revenue now expected to be more than $330 million and $380 million, respectively, increased from prior guidance of $320 million and $370 million, respectively FY 2024 and 2025 net income now expected to exceed $65 million and $115 million, respectively, increased from prior guidance of $60 million and $110 million, respectively FY 2024 Adjusted EBITDA now anticipated to exceed $90 million, increased from $85 million previously; FY 2025 Adjusted EBITDA expected to exceed $140 million Innovative Growth Opportunities: Below are the Company’s ongoing initiatives which, if successful, represent potential upside to newly provided guidance ranges: Biologic Production Yield Enhancement: The Company continues to progress with development scale and laboratory analyses, advancing the Company’s initiative to capture additional immune globulin (IG) production yields with the same quantities of starting raw material. These initiatives are subject to further evaluation, validation of commercial-scale production and requisite regulatory review. If proven successful, we believe these yield enhancements will potentially provide significant upside to the Company’s peak financial targets in the future. New Pipeline Introduction - S. pneumonia Hyperimmune Globulin: S. pneumonia is the primary cause of community-acquired pneumonia (CAP) in the United States, ranking ninth in overall mortality. The increasing prevalence of anti-infective resistance underscores the urgent need for both prophylactic and therapeutic interventions. Annually, about one million U.S. adults contract pneumococcal pneumonia, leading to 400,000 hospitalizations and a 5-7% mortality rate, with approximately 7,000 deaths attributed to anti-infective resistance. Despite available vaccines, vaccine-naive and immune-compromised patients remain at risk, highlighting the potential benefits of immediately available neutralizing antibodies provided by a hyperimmune globulin in both in-patient and out-patient settings. We estimate that, if approved, an S. pneumonia hyperimmune globulin could generate peak annual revenue of $300-500 million. ADMA holds various U.S. and foreign patents, including U.S. Patent Nos. 10,259,865 and 11,084,870, and EP Patent No. 3375789, each with patent terms extending to 2037, along with numerous pending applications. These patents cover ADMA’s proprietary pneumococcal hyperimmune technology, encompassing hyperimmune anti-pneumococcal immune globulin, methods of preparation, and utilization for treating S. pneumonia infections or providing immunotherapy to patients. During 2024, ADMA intends to advance pre-clinical work for the S. pneumonia program. ASCENIV Label Expansion: The ongoing post-marketing pediatric clinical study for ASCENIV may provide label expansion opportunities, further strengthening ADMA’s product portfolio compared to peers, if successful. Fourth Quarter 2023 Financial Results: Total revenues were $73.9 million for the quarter ended December 31, 2023, as compared to $50.0 million for the quarter ended December 31, 2022, an increase of $23.9 million, or approximately 48%. The increase is primarily related to increased sales of our immunoglobulin products, partially offset by a planned decrease in sales of plasma to third parties due to the increasing retention of plasma for internal intravenous immune globulin (IVIG) production. Adjusted EBITDA was $18.6 million for the quarter ended December 31, 2023, as compared to an Adjusted EBITDA loss of $3.5 million for the quarter ended December 31, 2022. Adjusted EBITDA for the quarter includes all non-GAAP reconciliation items, including stock-based compensation, depreciation, amortization and interest expense totaling $10.1 million and loss on debt extinguishment of $26.2 million. Net loss was $17.6 million for the quarter ended December 31, 2023, compared to a net loss of $12.2 million for the quarter ended December 31, 2022. Adjusted net income was $8.5 million for the quarter ended December 31, 2023, accounting for the non-GAAP reconciliation of a $26.2 million loss on extinguishment of debt incurred during the period, compared to an Adjusted net loss of $12.2 million for the quarter ended December 31, 2022. Full Year 2023 Financial Results: Total revenues were $258.2 million for the year ended December 31, 2023, as compared to $154.1 million for the year ended December 31, 2022, an increase of $104.1 million, or approximately 68%. The increase is primarily related to increased sales of our immunoglobulin products, partially offset by a planned decrease in sales of plasma to third parties due to the increasing retention of plasma for internal IVIG production. Adjusted EBITDA was $40.3 million for the year ended December 31, 2023, as compared to an Adjusted EBITDA loss of $27.6 million for the year ended December 31, 2022. Adjusted EBITDA for the full year includes all non-GAAP reconciliation items, including depreciation and amortization, interest expense, stock-based compensation, loss on debt extinguishment and costs related to the IT disruption. Net loss was $28.2 million for the year ended December 31, 2023, as compared to a net loss of $65.9 million for the year ended December 31, 2022. Adjusted net income was $0.7 million for the year ended December 31, 2023, accounting for the non-recurring costs related to the IT systems disruption totaling $2.8 million and the loss on extinguishment of debt totaling $26.2 million, as compared to Adjusted net loss of $59.2 million for the year ended December 31, 2022. As of December 31, 2023, ADMA had working capital of approximately $207.2 million, primarily consisting of $172.9 million of inventory, $51.4 million of cash and cash equivalents and $27.4 million of net accounts receivable, partially offset by current liabilities of $49.8 million, as compared to working capital at December 31, 2022 of $231.1 million, primarily consisting of $163.3 million of inventory, $86.5 million of cash and cash equivalents and $15.5 million of net accounts receivable, partially offset by current liabilities of $39.3 million. Conference Call Information To access the conference call seamlessly on February 28, 2024 at 4:30 PM ET, participants may register for the call here to receive the dial-in numbers and unique PIN. It is recommended that you join 10 minutes prior to the event starting (although you may register and dial in at any time during the call). A live audio webcast of the call will be available under “Events & Webcasts” in the investor section of the Company’s website, . An archived webcast will be available on the Company’s website approximately two hours after the event. About ASCENIV™ ASCENIV (immune globulin intravenous, human – slra 10% liquid) is a plasma-derived, polyclonal, intravenous immune globulin (IVIG). ASCENIV was approved by the United States Food and Drug Administration (FDA) in April 2019 and is indicated for the treatment of primary humoral immunodeficiency (PI), also known as primary immune deficiency disease (PIDD), in adults and adolescents (12 to 17 years of age). ASCENIV is manufactured using ADMA’s unique, patented plasma donor screening methodology and tailored plasma pooling design, which blends normal source plasma and respiratory syncytial virus (RSV) plasma obtained from donors tested using the Company’s proprietary microneutralization assay. ASCENIV contains naturally occurring polyclonal antibodies, which are proteins that are used by the body’s immune system to neutralize microbes, such as bacteria and viruses and prevent against infection and disease. ASCENIV is protected by U.S. Patents: 9,107,906, 9,714,283 and 9,815,886. Certain data and other information about ASCENIV can be found by visiting Information about ADMA and its products can be found on the Company’s website at Additional Important Safety Information About ASCENIV™ WARNING: THROMBOSIS, RENAL DYSFUNCTION AND ACUTE RENAL FAILURE Thrombosis may occur with immune globulin intravenous (IGIV) products, including ASCENIV. 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. Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with the administration of IGIV products in predisposed patients. Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. ASCENIV does not contain sucrose. For patients at risk of thrombosis, renal dysfunction or renal failure, administer ASCENIV 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. ASCENIV™ Contraindications: History of anaphylactic or severe systemic reactions to human immunoglobulin. IgA deficient patients with antibodies to IgA and a history of hypersensitivity. ASCENIV™ Warnings and Precautions: IgA-deficient patients with antibodies against IgA are at greater risk of developing severe hypersensitivity and anaphylactic reactions. Have medications such as epinephrine available to treat any acute severe hypersensitivity reactions. [4, 5.1] Thrombotic events have occurred in patients receiving IGIV treatments. Monitor patients with known risk factors for thrombotic events; consider baseline assessment of blood viscosity for patients at risk of hyperviscosity. [5.2, 5.4] In patients at risk of developing acute renal failure. monitor renal function, including blood urea nitrogen (BUN), serum creatinine, and urine output. [5.3, 5.9] Hyperproteinemia, increased serum viscosity, and hyponatremia or pseudohyponatremia can occur in patients receiving IGIV treatment. Aseptic meningitis syndrome (AMS) has been reported with IGIV treatments, especially with high doses or rapid infusion. [5.5] Hemolytic anemia can develop subsequent to IGIV treatment. Monitor patients for hemolysis and hemolytic anemia. [5.6] Monitor patients for pulmonary adverse reactions (Transfusion-related acute lung injury [TRALI]). If transfusion related acute lung injury is suspected, test the product and patient for antineutrophil antibodies. [5.7] Because this product is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. ASCENIV™ Adverse Reactions: The most common adverse reactions to ASCENIV (≥5% of study subjects) were headache, sinusitis, diarrhea, gastroenteritis viral, nasopharyngitis, upper respiratory tract infection, bronchitis, and nausea To report SUSPECTED ADVERSE REACTIONS, contact ADMA Biologics at (800) 458-4244 or FDA at 1-800-FDA-1088 or . About ADMA Biologics, Inc. (ADMA) ADMA Biologics is an end-to-end commercial biopharmaceutical company dedicated to manufacturing, marketing and developing specialty biologics for the treatment of immunodeficient patients at risk for infection and others at risk for certain infectious diseases. ADMA currently manufactures and markets three United States Food and Drug Administration (FDA)-approved plasma-derived biologics for the treatment of immune deficiencies and the prevention of certain infectious diseases: BIVIGAM® (immune globulin intravenous, human) for the treatment of primary humoral immunodeficiency (PI); ASCENIV™ (immune globulin intravenous, human – slra 10% liquid) for the treatment of PI; and NABI-HB® (hepatitis B immune globulin, human) to provide enhanced immunity against the hepatitis B virus. ADMA manufactures its immune globulin products at its FDA-licensed plasma fractionation and purification facility located in Boca Raton, Florida. Through its ADMA BioCenters subsidiary, ADMA also operates as an FDA-approved source plasma collector in the U.S., which provides its blood plasma for the manufacture of its products. ADMA’s mission is to manufacture, market and develop specialty biologics, human immune globulins targeted to niche patient populations for the treatment and prevention of certain infectious diseases and management of immune compromised patient populations who suffer from an underlying immune deficiency, or who may be immune compromised for other medical reasons. ADMA holds numerous U.S. and foreign patents related to and encompassing various aspects of its products and product candidates. For more information, please visit . Use of Non-GAAP Financial Measures This press release includes certain non-GAAP financial measures that are not prepared in accordance with accounting principles generally accepted in the United States (“GAAP”). The Company believes Adjusted EBITDA/(loss) and Adjusted net income/(loss) are useful to investors in evaluating the Company’s financial performance. The Company uses Adjusted EBITDA/(loss) and Adjusted net income/(loss) as key performance measures because we believe that they facilitate operating performance comparisons from period to period that exclude potential differences driven by the impact of variations of non-cash items such as depreciation and amortization, as well as, in the case of Adjusted EBITDA, stock-based compensation or certain non-recurring items, and in the case of Adjusted net income, certain non-recurring items. The Company believes that investors should have access to the same set of tools used by our management and board of directors to assess our operating performance. Adjusted EBITDA/(loss) and Adjusted net income/(loss) should not be considered as measures of financial performance under GAAP, and the items excluded from Adjusted EBITDA/(loss) and Adjusted net income/(loss) are significant components in understanding and assessing the Company’s financial performance. Accordingly, these key business metrics have limitations as an analytical tool. They should not be considered as an alternative to net income/loss or any other performance measures derived in accordance with GAAP and may be different from similarly titled non-GAAP measures used by other companies. Please refer to the tables below for the reconciliation of GAAP measures to these non-GAAP measures for applicable periods. Cautionary Note Regarding Forward-Looking Statements This press release contains “forward-looking statements” pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, about ADMA Biologics, Inc. (“we,” “our” or the “Company”). Forward-looking statements include, without limitation, any statement that may predict, forecast, indicate, or imply future results, performance or achievements, and may contain such words as “confident,” “estimate,” “project,” “intend,” “forecast,” “target,” “anticipate,” “plan,” “planning,” “expect,” “believe,” “will,” “is likely,” “will likely,” “should,” “could,” “would,” “may,” or, in each case, their negative, or words or expressions of similar meaning. These forward-looking statements include, but are not limited to, statements about the Company’s future results of operations, including, but not limited to, revenue, net income and Adjusted EBITDA guidance in future periods, and certain assumptions in connection therewith; the market for ASCENIV and BIVIGAM; and additional growth opportunities, including but not limited to, the Company’s yield enhancement initiative, the newly announced hIG pipeline program targeting S. pneumonia (including the revenue potential) and ASCENIV label expansion. Actual events or results may differ materially from those described in this press release due to a number of important factors. Current and prospective security holders are cautioned that there also can be no assurance that the forward-looking statements included in this press release will prove to be accurate. Except to the extent required by applicable laws or rules, ADMA does not undertake any obligation to update any forward-looking statements or to announce revisions to any of the forward-looking statements. Forward-looking statements are subject to many risks, uncertainties and other factors that could cause our actual results, and the timing of certain events, to differ materially from any future results expressed or implied by the forward-looking statements, including, but not limited to, the risks and uncertainties described in our filings with the U.S. Securities and Exchange Commission, including our most recent reports on Form 10-K, 10-Q and 8-K, and any amendments thereto. COMPANY CONTACT: Skyler Bloom Senior Director, Corporate Strategy and Business Development | 201-478-5552 | sbloom@admabio.com INVESTOR RELATIONS CONTACT: Michelle Pappanastos Senior Managing Director, Argot Partners | 212-600-1902 | michelle@argotpartners.com ADMA BIOLOGICS, INC. AND SUBSIDIARIES CONSOLIDATED STATEMENTS OF OPERATIONS Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 (Unaudited) (Unaudited) (in thousands, except share and per share amounts) REVENUES $ 73,904 $ 49,981 $ 258,215 $ 154,080 Cost of product revenue 42,817 35,804 169,273 118,815 Gross profit 31,087 14,177 88,942 35,265 OPERATING EXPENSES: Research and development 445 1,074 3,300 3,614 Plasma center operating expenses 685 5,088 4,266 17,843 Amortization of intangible assets 187 179 724 715 Selling, general and administrative 15,535 13,895 59,020 52,458 Total operating expenses 16,852 20,236 67,310 74,630 INCOME (LOSS) FROM OPERATIONS 14,235 (6,059 ) 21,632 (39,365 ) OTHER INCOME (EXPENSE): Interest income 612 2 1,617 45 Interest expense (6,215 ) (5,737 ) (25,027 ) (19,279 ) Loss on extinguishment of debt (26,174 ) - (26,174 ) (6,670 ) Other expense (101 ) (438 ) (287 ) (635 ) Other expense, net (31,878 ) (6,173 ) (49,871 ) (26,539 ) NET LOSS $ (17,643 ) $ (12,232 ) $ (28,239 ) $ (65,904 ) BASIC AND DILUTED LOSS PER COMMON SHARE $ (0.08 ) $ (0.06 ) $ (0.13 ) $ (0.33 ) WEIGHTED AVERAGE COMMON SHARES OUTSTANDING: Basic and Diluted 225,968,387 202,830,446 223,977,315 197,874,895 ADMA BIOLOGICS, INC. AND SUBSIDIARIES CONSOLIDATED BALANCE SHEETS December 31, December 31, 2023 2022 (Unaudited) (In thousands, except share data) ASSETS Current assets: Cash and cash equivalents $ 51,352 $ 86,522 Accounts receivable, net 27,421 15,505 Inventories 172,906 163,280 Prepaid expenses and other current assets 5,334 5,095 Total current assets 257,013 270,402 Property and equipment, net 53,835 58,261 Intangible assets, net 499 1,013 Goodwill 3,530 3,530 Right-to-use assets 9,635 10,485 Deposits and other assets 4,670 4,770 TOTAL ASSETS $ 329,182 $ 348,461 LIABILITIES AND STOCKHOLDERS' EQUITY Current liabilities: Accounts payable $ 15,660 $ 13,229 Accrued expenses and other current liabilities 32,919 24,990 Current portion of deferred revenue 182 143 Current portion of lease obligations 1,045 905 Total current liabilities 49,806 39,267 Senior notes payable, net of discount 130,594 142,833 Deferred revenue, net of current portion 1,690 1,833 End of term fee 1,688 1,500 Lease obligations, net of current portion 9,779 10,704 Other non-current liabilities 419 350 TOTAL LIABILITIES 193,976 196,487 COMMITMENTS AND CONTINGENCIES STOCKHOLDERS' EQUITY Preferred Stock, $0.0001 par value, 10,000,000 shares authorized, no shares issued and outstanding - - Common Stock - voting, $0.0001 par value, 300,000,000 shares authorized, 226,063,032 and 221,816,930 shares issued and outstanding 23 22 Additional paid-in capital 641,439 629,969 Accumulated deficit (506,256 ) (478,017 ) TOTAL STOCKHOLDERS' EQUITY 135,206 151,974 TOTAL LIABILITIES AND STOCKHOLDERS' EQUITY $ 329,182 $ 348,461 NON-GAAP RECONCILIATION RECONCILIATION OF GAAP NET (LOSS) TO ADJUSTED NET INCOME (LOSS) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 (Unaudited) (Unaudited) Net loss $ (17,643 ) $ (12,232 ) $ (28,239 ) $ (65,904 ) Loss on extinguishment of debt 26,174 - 26,174 6,670 IT systems disruption - - 2,770 - Adjusted net income (loss) $ 8,531 $ (12,232 ) $ 705 $ (59,234 ) NON-GAAP RECONCILIATION RECONCILIATION OF GAAP NET LOSS TO ADJUSTED EBITDA Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 (Unaudited) (Unaudited) Net loss $ (17,643 ) $ (12,232 ) $ (28,239 ) $ (65,904 ) Depreciation 1,921 1,758 7,608 6,398 Amortization 188 178 724 715 Interest expense 6,215 5,737 25,027 19,279 EBITDA (9,319 ) (4,559 ) 5,120 (39,512 ) Stock-based compensation 1,745 1,069 6,187 5,215 IT systems disruption - - 2,770 - Loss on extinguishment of debt 26,174 - 26,174 6,670 Adjusted EBITDA $ 18,600 $ (3,490 ) $ 40,251 $ (27,627 )

OSAKA, Japan & CAMBRIDGE, MA, USA I January 29, 2024 I Takeda ( TSE:4502/NYSE:TAK ) today announced that the U.S. Food and Drug Administration (FDA) has approved GAMMAGARD LIQUID ® [Immune Globulin Infusion (Human) 10% solution] as an intravenous immunoglobulin (IVIG) therapy to improve neuromuscular disability and impairment in adults with chronic inflammatory demyelinating polyneuropathy (CIDP). 1 It can be used as induction therapy, which includes an induction dose followed by maintenance doses. 1 For treatment of CIDP, GAMMAGARD LIQUID has not been studied in immunoglobulin-naive patients nor as maintenance therapy for periods longer than six months. 1 This milestone follows the recent FDA approval of HYQVIA ® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] for maintenance therapy to prevent the relapse of neuromuscular disability and impairment in adults with CIDP. 2 HYQVIA is the only combination of immunoglobulin (IG) and hyaluronidase, which makes it a facilitated subcutaneous IG infusion. 2 “The approval of GAMMAGARD LIQUID for treatment of CIDP is an encouraging validation of our decades-long commitment to advancing plasma-derived therapies on behalf of people living with rare neuromuscular disorders and bringing our portfolio of differentiated IG therapies to these patients,” said Richard Ascroft, senior vice president and head of Takeda’s U.S. Plasma-Derived Therapies Business Unit. “Together with the recent HYQVIA approval in the U.S., we can now offer induction and maintenance therapy options to adults living with CIDP that may accommodate their personal treatment needs.” The approval is based on results from a prospective, open-label, single-arm, multicenter clinical study (ADVANCE-CIDP 2) that evaluated the efficacy and safety of GAMMAGARD LIQUID in adults with CIDP who developed a relapse in the randomized, double-blinded, placebo-controlled study evaluating efficacy, safety and tolerability of HYQVIA (ADVANCE-CIDP 1) in adults with CIDP. Efficacy in ADVANCE-CIDP 2 was based on responder rate, where a responder was defined as a subject who demonstrated an improvement of functional disability. The responder rate was 94.4% (N=18, 95% CI: 74.2% to 99.0%). Improvement in grip strength and change in Rasch-built Overall Disability Scale (R-ODS) score were recorded across participants. 1 The most common adverse reactions observed in ≥5% of clinical study patients were headache, pyrexia, anemia, leukopenia, neutropenia, illness, blood creatinine increased, dizziness, migraine, somnolence, tremor, nasal dryness, abdominal pain upper, vomiting, chills, nasopharyngitis and pain in extremity. 1 CIDP is a rare, acquired, immune-mediated neuromuscular disorder affecting the peripheral nervous system. 3,4 It is characterized by progressive, symmetric symptoms such as weakness, tingling or loss of feeling in distal and proximal limbs, loss of reflexes and difficulty walking. 3 Because its symptoms may overlap with other rare, neuromuscular conditions, CIDP may be misdiagnosed. 5 The mechanism of action of immunoglobulins in the treatment of CIDP in adults has not been fully elucidated but may include immunomodulatory effects. 1 “As the standard of care for the treatment of CIDP, IG therapy is thought to help normalize compromised immune systems through immunomodulatory mechanisms,” said Dr. Mamatha Pasnoor, professor in the Department of Neurology at the University of Kansas Medical Center. “Because CIDP is a progressive and complex disease, multiple treatment options are needed, and clinicians now have an additional therapy that can help adults with CIDP manage their disease.” GAMMAGARD LIQUID is the only IVIG with multiple neuromuscular disorder indications in the U.S. since it is now approved for CIDP and it is the only FDA-approved IVIG to treat multifocal motor neuropathy as a maintenance therapy to improve muscle strength and disability in adults. 1 It is also indicated in the U.S. as a replacement therapy for people two years of age or older living with primary immunodeficiency. 1 About GAMMAGARD LIQUID GAMMAGARD LIQUID ® [Immune Globulin Infusion (Human) 10% solution] is an intravenous immunoglobulin (IVIG) that is infused into the veins. GAMMAGARD LIQUID is approved in the U.S. as an IG therapy to improve neuromuscular disability and impairment in adult patients with CIDP, as a replacement therapy for primary immunodeficiency (PI) in adult and pediatric patients two years of age and older, and as a maintenance therapy to improve muscle strength and disability in adult patients with multifocal motor neuropathy (MMN). Also known as KIOVIG outside the U.S. and Canada, it is approved in 66 countries worldwide. About HYQVIA HYQVIA ® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] is a liquid medicine containing Recombinant Human Hyaluronidase and immunoglobulin (IG) and is approved in the U.S. 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. 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). About ADVANCE-CIDP 2 ADVANCE-CIDP 2 was a prospective, open-label, single-arm, multicenter clinical study that evaluated the efficacy and safety of GAMMAGARD LIQUID in adults with CIDP who developed a relapse in the randomized, double-blinded, placebo-controlled study evaluating efficacy, safety and tolerability of HYQVIA (ADVANCE-CIDP 1) in adults with CIDP. The 18 patients who relapsed during ADVANCE-CIDP 1 were offered enrollment in ADVANCE-CIDP 2. GAMMAGARD LIQUID was administered at an induction dose of 2 g/kg body weight, followed by maintenance infusions at every three weeks for a period of six months. The dose of GAMMAGARD LIQUID treatment could be adjusted at the investigator's discretion. Adjustments to the dosing interval of every three weeks were not allowed. All subjects completed the study. All dosed subjects were analyzed for efficacy and safety. Efficacy of ADVANCE-CIDP 2 was based on responder rate, where a responder is defined as subjects who had at least a one-point decrease in the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score at the completion of the treatment period (six months). The responder rate was 94.4% (N=18, 95% CI: 74.2% to 99.0%). The INCAT score returned to baseline values prior to joining the study in 17 of the 18 subjects (94.4%) at six months. All subjects had improvement in functional ability as defined by a composite outcome metrics that included INCAT score, grip strength, or Rasch-built Overall Disability Scale (R-ODS) score. Further information about the ADVANCE-CIDP 2 study is available at ClinicalTrials.gov under study identifier NCT02549170 . INDICATIONS GAMMAGARD LIQUID is indicated as replacement therapy for Primary Humoral Immunodeficiency (PI) in adult and pediatric patients ≥2 years, as a maintenance therapy to improve muscle strength and disability in adult patients with Multifocal Motor Neuropathy (MMN), and as a therapy to improve neuromuscular disability and impairment in adult patients with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). LIMITATIONS OF USE (CIDP): GAMMAGARD LIQUID has not been studied in immunoglobulin-naive patients with CIDP. GAMMAGARD LIQUID maintenance therapy in CIDP has not been studied for periods longer than 6 months. After responding during an initial treatment period, not all patients require indefinite maintenance therapy with GAMMAGARD LIQUID in order to remain free of CIDP symptoms. Individualize the duration of any treatment beyond 6 months based upon the patient’s response and demonstrated need for continued therapy. 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. GAMMAGARD LIQUID for PI is for intravenous or subcutaneous use. GAMMAGARD LIQUID for MMN and CIDP is for intravenous use only. IMPORTANT SAFETY INFORMATION WARNING: THROMBOSIS HYQVIA and GAMMAGARD LIQUID WARNING: RENAL DYSFUNCTION and ACUTE RENAL FAILURE GAMMAGARD LIQUID Contraindications Warnings and Precautions Hypersensitivity: Severe hypersensitivity reactions may occur, even in patients who have tolerated previous treatment with human IG. 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. Renal Dysfunction/Failure: Acute renal dysfunction/failure, acute tubular necrosis, proximal tubular nephropathy, osmotic nephrosis, and death may occur with IV use of IG products, especially those containing sucrose. Acute renal dysfunction/failure has been reported in association with infusions of GAMMAGARD LIQUID . 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, assess renal function before initiation and throughout treatment, and consider lower, more frequent dosing. If renal function deteriorates, consider discontinuation. 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. Aseptic Meningitis Syndrome: Has been reported with use of IG, including HYQVIA and may occur more frequently in females. 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. The syndrome usually begins within several hours to two days following IG treatment. Hemolysis: HYQVIA and GAMMAGARD LIQUID contain 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. Transfusion-Related Acute Lung Injury: Non-cardiogenic pulmonary edema has been reported with IV-administered IG, including GAMMAGARD LIQUID . 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. May be managed using oxygen therapy with adequate ventilatory support. Transmittable Infectious Agents: Because HYQVIA and GAMMAGARD LIQUID are made from human plasma, they may carry a risk of transmitting infectious agents (e.g., viruses, other pathogens). No confirmed cases of viral transmission of variant Creutzfeldt-Jakob disease (vCJD) have been associated with GAMMAGARD LIQUID , and no cases have been associated with HYQVIA . 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. Additional Warnings and Precautions for HYQVIA Immunogenicity of Recombinant Human Hyaluronidase (rHuPH20 ): Non-neutralizing antibodies to the Recombinant Human Hyaluronidase component can develop. The clinical significance of these antibodies or whether they interfere with fertilization in humans is unknown. Spread of Localized Infection: Do not infuse HYQVIA into or around an infected area due to potential risk of spreading a localized infection. Additional Warnings and Precautions for GAMMAGARD LIQUID Hyperproteinemia, increased serum viscosity, and hyponatremia may occur. It is critical to distinguish true hyponatremia from a pseudohyponatremia because certain treatments may lead to volume depletion, a further increase in serum viscosity, and a predisposition to thromboembolic events. Adverse Reactions HYQVIA The most common adverse reactions observed in >5% of patients in the clinical trials were: PI: local adverse reactions including pain, erythema, edema, and pruritus, and systemic adverse reactions including, headache, antibody formation against Recombinant Human Hyaluronidase (rHuPH20), fatigue, nausea, pyrexia, and vomiting. CIDP: local reactions, headache, pyrexia, nausea, fatigue, erythema, pruritus, increased lipase, abdominal pain, back pain, and pain in extremity. GAMMAGARD LIQUID The most serious adverse reactions observed in clinical studies in PI was aseptic meningitis, and in MMN were pulmonary embolism and blurred vision. The most common adverse reactions observed in ≥5% of patients in the clinical trials were: IV administration for PI: Headache, fatigue, pyrexia, nausea, chills, rigors, pain in extremity, diarrhea, migraine, dizziness, vomiting, cough, urticaria, asthma, pharyngolaryngeal pain, rash, arthralgia, myalgia, oedema peripheral, pruritus, and cardiac murmur. Subcutaneous administration for PI: Infusion site (local) event (rash, erythema, edema, hemorrhage, and irritation), headache, fatigue, heart rate increased, pyrexia, abdominal pain upper, nausea, vomiting, asthma, blood pressure systolic increased, diarrhea, ear pain, aphthous stomatitis, migraine, oropharyngeal pain, and pain in extremity. IV administration for MMN: Headache, chest discomfort, muscle spasms, muscular weakness, nausea, oropharyngeal pain, and pain in extremity. IV administration for CIDP: Headache, pyrexia, anemia, leukopenia, neutropenia, illness, blood creatinine increased, dizziness, migraine, somnolence, tremor, nasal dryness, abdominal pain upper, vomiting, chills, nasopharyngitis, 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. For Full U.S. Prescribing Information for GAMMAGARD LIQUID, please visit: https://www.shirecontent.com/PI/PDFs/GAMLIQUID_USA_ENG.pdf For Full U.S. Prescribing Information for HYQVIA, please visit: https://www.shirecontent.com/PI/PDFs/HYQVIA_USA_ENG.pdf About Takeda Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit www.takeda.com . 1 GAMMAGARD LIQUID ® [Immune Globulin Infusion (Human) 10% solution] U.S. Prescribing Information. https://www.shirecontent.com/PI/PDFs/GAMLIQUID_USA_ENG.pdf 2 HYQVIA ® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] U.S. Prescribing Information. https://www.shirecontent.com/PI/PDFs/HYQVIA_USA_ENG.pdf 3 Dalakas MC. Nat Rev Neurol . 2011;7(9):507–17. 4 GBS CIDP Foundation International. Voice of the Patient Report. August 26, 2022. www.gbs-cidp.org . Accessed August 2022. 5 Broers MC, Bunschoten C, Nieboer D, Lingsma HF, Jacobs BC. Eur J Neurol . 2021;28(6):2065-2073. SOURCE: Takeda Pharmaceutical Co

OSAKA, Japan & CAMBRIDGE, Mass.--( BUSINESS WIRE )--Takeda ( TSE:4502/NYSE:TAK ) today announced that the U.S. Food and Drug Administration (FDA) has approved HYQVIA ® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent the relapse of neuromuscular disability and impairment in adults. HYQVIA first received approval in the U.S. in 2014 for the treatment of primary immunodeficiency (PI) in adults, which has since been expanded to include children 2-16 years old. 1 HYQVIA is the only FDA-approved combination of immunoglobulin (IG) and hyaluronidase, which makes it a facilitated subcutaneous immunoglobulin (SCIG) infusion. For adults with CIDP, HYQVIA can be infused up to once monthly (every two, three or four weeks) due to the hyaluronidase component, which facilitates the dispersion and absorption of large IG volumes in the subcutaneous space between the skin and the muscle. Because it is delivered subcutaneously, HYQVIA can be administered by a healthcare professional in a medical office, infusion center or at a patient’s home. In addition, it can be self-administered after appropriate patient or caregiver training. 1 “ With the FDA approval of HYQVIA for CIDP, which builds on our expertise in rare neuroimmunological and neuromuscular disorders, we can now offer a personalized maintenance treatment option for adults with this debilitating disease,” said Giles Platford, president of Takeda’s Plasma-Derived Therapies Business Unit. “ Research and clinical experience have shown that IG therapy is effective as maintenance treatment in adults with CIDP, and we hope that this approval for HYQVIA is the first of several around the world as we strive to deliver our broad and diverse IG portfolio to more people with complex neuroimmunological diseases.” This approval is based on results from a randomized, double-blinded, placebo-controlled study (ADVANCE-CIDP 1) and a single-arm, open-label, extension study (ADVANCE-CIDP 3) that evaluated the efficacy and safety of HYQVIA as a maintenance therapy in adults with CIDP. The efficacy evaluation included 122 adults from ADVANCE-CIDP 1 with a confirmed diagnosis of CIDP and who had remained on a stable dosing regimen of intravenous immunoglobulin (IVIG) therapy for at least three months prior to screening. The analysis of the primary endpoint demonstrated a statistically significant difference between the relapse rates in the HYQVIA group (N=57, 14.0%) compared to the placebo group (N=65, 32.3%) (p=0.0314). The treatment difference of -18.3% (two-sided 95% CI: -32.1%, -3.1%) indicated that HYQVIA demonstrated superiority over placebo in preventing relapse of CIDP. 1 The safety of HYQVIA in adults with CIDP was evaluated across ADVANCE-CIDP 1 (N=62) and ADVANCE-CIDP 3 (N=79). The most common adverse reactions observed in >5% of study subjects in clinical studies of HYQVIA for CIDP were local reactions, headache, pyrexia, nausea, fatigue, erythema, pruritus, increased lipase, abdominal pain, back pain, and pain in extremity. 1 CIDP is a rare, acquired, immune-mediated neuromuscular disorder affecting the peripheral nervous system. 2,3 It is typically characterized by progressive, symmetric symptoms such as weakness, tingling or loss of feeling in distal and proximal limbs, loss of reflexes and difficulty walking. 3 Because its symptoms may overlap with other rare, neuromuscular conditions, CIDP is often misdiagnosed. 4 The mechanism of action of IG in the treatment of CIDP in adults has not been fully elucidated but may include immunomodulatory effects. 1 The role of IG therapy as maintenance treatment in CIDP has been well-established and is the guidelines-based standard of care for this complex and heterogeneous condition. 5 However, there are aspects of IVIG treatment that can be challenging for patients such as long treatment duration associated with high IG volumes, potential for venous access challenges, and infusion setting limitations. 5 “ While it is considered the standard-of-care for maintenance treatment of adults with CIDP, IVIG infusions may be challenging for some patients and their caregivers,” said Lisa Butler, executive director, GBS-CIDP Foundation International. “ We’re excited that this therapy could offer some adults with CIDP an alternative subcutaneous option that may address some of these challenges and help personalize treatment.” HYQVIA is now available as a maintenance therapy for adult patients with CIDP in the U.S. In December 2023, Takeda announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of HYQVIA as maintenance therapy in patients with CIDP after stabilization with IVIG. The European Commission (EC) will consider the CHMP positive opinion when determining the potential marketing authorization for HYQVIA for CIDP throughout the European Union. 6 About HYQVIA HYQVIA ® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] is a liquid medicine containing Recombinant Human Hyaluronidase and immunoglobulin (IG) and is approved in the U.S. 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. 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). About ADVANCE-CIDP 1 and ADVANCE-CIDP 3 ADVANCE-CIDP 1 was a Phase 3, multicenter, placebo-controlled, double-blinded study evaluating the safety, efficacy and tolerability of HYQVIA. The primary endpoint of the ADVANCE-CIDP 1 clinical trial was the proportion of subjects who experienced a relapse, defined as an increase of ≥1 point relative to the pre-subcutaneous (SC) treatment baseline score in two consecutive adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores obtained less than seven days apart. Patients were randomized to receive either HYQVIA or placebo at the same dose and infusion frequency as their prior IVIG treatment (every two, three or four weeks) for six months or until withdrawal or relapse. Those who remained relapse free were offered HYQVIA treatment as part of ADVANCE-CIDP 3, which was an open-label extension clinical trial to assess the long-term safety, tolerability and immunogenicity of HYQVIA in participants with CIDP who completed ADVANCE-CIDP 1. Further information about the ADVANCE-CIDP 1 and ADVANCE-CIDP 3 clinical trials is available at ClinicalTrials.gov under study identifiers NCT02549170 and NCT02955355 , respectively. HYQVIA U.S. Indication 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. HYQVIA U.S. Important Safety Information WARNING: THROMBOSIS Thrombosis may occur with immune globulin (IG) products, including HYQVIA. 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. Thrombosis may occur in the absence of known risk factors. For patients at risk of thrombosis, administer HYQVIA 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 of hyperviscosity. 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 who have tolerated previous treatment with human IG. 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): Non-neutralizing antibodies to the Recombinant Human Hyaluronidase component can develop. The clinical significance of these antibodies or whether they interfere with fertilization in humans is unknown. Aseptic Meningitis Syndrome: Has been reported with use of IG, including HYQVIA and may occur more frequently in females. 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, and death may occur with intravenous (IV) use of IG products, especially those containing sucrose. 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, 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. May be managed using oxygen therapy with adequate ventilatory support. Transmittable Infectious Agents: Because HYQVIA is made from human plasma, it may carry a risk of transmitting infectious agents (e.g. viruses, other pathogens). No cases of transmission of viral diseases or variant Creutzfeldt-Jakob disease (vCJD) have been associated with HYQVIA. 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 adverse reactions including pain, erythema, edema, and pruritus, and systemic adverse reactions including, headache, antibody formation against Recombinant Human Hyaluronidase (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. For Full U.S. Prescribing Information, please visit: https://www.shirecontent.com/PI/PDFs/HYQVIA_USA_ENG.pdf For European Union Summary of Product Characteristics, please visit: https://www.ema.europa.eu/en/medicines/human/EPAR/hyqvia About Takeda Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit www.takeda.com . Important Notice For the purposes of this notice, “press release” means this document, any oral presentation, any question and answer session and any written or oral material discussed or distributed by Takeda Pharmaceutical Company Limited (“Takeda”) regarding this release. 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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. _______________________ 1 HYQVIA ® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] U.S. Prescribing Information. 2 GBS CIDP Foundation International. Voice of the Patient Report. August 26, 2022. www.gbs-cidp.org . Accessed August 2022. 3 Dalakas MC. Nat Rev Neurol . 2011;7(9):507–17. 4 Broers MC, Bunschoten C, Nieboer D, Lingsma HF, Jacobs BC. Eur J Neurol . 2021;28(6):2065–2073. 5 Van den Bergh P, Van Doorn PA, Hadden RD, et al. Eur J Neurol . 2021;28(11):3556–3583. 6 European Medicines Agency. HyQvia 100 mg/mL solution for infusion for subcutaneous use Summary of Product Characteristics. https://www.ema.europa.eu/en/documents/product-information/hyqvia-epar-product-information_en.pdf .