Grifols achieves positive topline results from phase 4 study of XEMBIFY® (immune globulin subcutaneous human-klhw) evaluating biweekly dosing option for patients

Barcelona, Spain, July 20, 2023 – Grifols (MCE: GRF, MCE: GRF.P NASDAQ: GRFS), one of the world’s leading producers of plasma-derived medicines, today announced that its recently concluded phase 4 trial (NCT04566692) evaluating a biweekly dosing of XEMBIFY^® has met its primary endpoint. It has demonstrated that patients with primary immunodeficiencies (PIDs) treated with this subcutaneous 20% immunoglobulin (SCIg) product every two weeks achieved non-inferiority in total Ig levels compared with those who received the medication weekly.

The phase 4 trial also demonstrated similarly good safety and tolerability profiles between biweekly and weekly administration. It was a multicenter, single-sequence, open-label clinical study that included 27 subjects across 18 U.S. sites.

Results will support the potential product labeling extension of XEMBIFY^® to include biweekly dosing, pending review and approval by the United States Food and Drug Administration. This option is already available in the European markets where it is authorized.

“Patients using XEMBIFY^® could have an additional dosing option to choose from, providing more convenience and flexibility when controlling their immunodeficiencies,” said Kim Hanna, Grifols Senior Director Clinical Development. “Grifols is committed to strengthening its portfolio of leading immunoglobulin therapeutics to meet the growing demand as the number of people living with immunodeficiencies continues to increase.”

With demonstrated efficacy and tolerability, XEMBIFY^® is indicated for PIDs in the U.S. and both primary and select secondary immunodeficiencies (SIDs) in Europe, Canada and Australia.

The global market for Ig is expected to grow in the high single digits in the coming years as a result of the increase in PIDs and SIDs, which together account for up to 55% of the total Ig market.¹ SIDs have notably risen due to an aging population and the use of immunosuppressive therapies, such as immuno-oncology treatments, for which Ig is the preferred and only option.

About XEMBIFY^®

Grifols XEMBIFY^® is a 20% solution of purified human immunoglobulin (primarily immune globulin G [IgG]) made from large pools of human plasma via modifications of the Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-C 10%) manufacturing process.

INDICATION

XEMBIFY^® (immune globulin subcutaneous human–klhw) is a 20% immune globulin indicated for treatment of primary humoral immunodeficiency disease (PIDD) in patients 2 years of age and older. XEMBIFY^® is for subcutaneous administration only.

IMPORTANT SAFETY INFORMATION

WARNING: THROMBOSIS

• Thrombosis may occur with immune globulin products, including XEMBIFY^®. Risk factors may include: advanced age, prolonged immobilization, 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 XEMBIFY^®. 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

XEMBIFY^® is contraindicated in patients who have had an anaphylactic or severe systemic reaction to the administration of human immune globulin. It is contraindicated in IgA-deficient patients with antibodies against IgA and a history of hypersensitivity.

Warnings and Precautions

Hypersensitivity. Severe hypersensitivity reactions may occur with immune globulin products, including XEMBIFY^®. In case of hypersensitivity, discontinue infusion immediately and institute appropriate treatment. XEMBIFY contains IgA. Patients with known antibodies to IgA may have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions.

Thrombosis. Thrombosis may occur following treatment with immune globulin products, including XEMBIFY^®. Thrombosis may occur 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 of hyperviscosity.

Aseptic meningitis syndrome (AMS). AMS may occur with human immune globulin treatment, including XEMBIFY^®. Conduct a thorough neurological exam on patients exhibiting signs and symptoms to rule out other causes of meningitis. Discontinuation of treatment has resulted in remission within several days without sequelae.

Renal dysfunction/failure. Acute renal dysfunction/failure, acute tubular necrosis, proximal tubular nephropathy, osmotic nephrosis, and death may occur with use of human immune globulin products, especially those containing sucrose. XEMBIFY^®  does not contain sucrose. Ensure patients are not volume-depleted prior to starting infusion. In patients at risk due to preexisting renal insufficiency or predisposition to acute renal failure, assess renal function prior to the initial infusion of XEMBIFY^®  and again at appropriate intervals thereafter. If renal function deteriorates, consider discontinuation.

Hemolysis. XEMBIFY^®  may contain blood group antibodies that may cause a positive direct antiglobulin reaction and hemolysis. Monitor patients for clinical signs and symptoms of hemolysis. If signs and symptoms are present after infusion, perform confirmatory lab testing.

Transfusion-related acute lung injury (TRALI). Noncardiogenic pulmonary edema may occur in patients following treatment with immune globulin products, including XEMBIFY^®. Monitor patients for pulmonary adverse reactions. If TRALI is suspected, perform appropriate tests for the presence of antineutrophil and anti-HLA antibodies in both the product and patient serum. TRALI may be managed using oxygen therapy with adequate ventilatory support.

Transmissible infectious agents. Because XEMBIFY^®  is made from human blood, it may carry a risk of transmitting infectious agents, eg, viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. No cases of transmission of viral diseases, vCJD, or CJD have ever been associated with the use of XEMBIFY^®.

Interference with lab tests. After infusion of XEMBIFY^®, passively transferred antibodies in the patient’s blood may yield positive serological testing results, with the potential for misleading interpretation.

Adverse Reactions

The most common adverse reactions in ≥ 5% of subjects in the clinical trial were local adverse reactions, including infusion-site erythema (redness), infusion-site pain, infusion-site swelling (puffiness), infusion-site bruising, infusion-site nodule, infusion-site pruritus (itching), infusion-site induration (firmness), infusion-site scab, infusion-site edema, and systemic reactions including cough and diarrhea.

Drug Interactions

Passive transfer of antibodies may transiently interfere with the immune responses to live attenuated virus vaccines (eg, measles, mumps, rubella, and varicella).

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Please see full Prescribing Information for XEMBIFY^®  or visit www.xembify.com

Globally, prescribing information varies; refer to the individual country product label for complete information.