FDA Approves Takeda’s Immune Globulin Infusion, Hyqvia, for Chronic Inflammatory Demyelinating Polyneuropathy

The FDA has approved immune globulin (IG) infusion 10% (human) with recombinant human hyaluronidase (Hyqvia; Takeda Pharmaceuticals), a liquid medicine, as maintenance therapy for adults with chronic inflammatory demyelinating polyneuropathy (CIDP) to prevent relapse of neuromuscular disability and impairment. Hyqvia is the only FDA-approved combination of IG and hyaluronidase, which makes it a facilitated subcutaneous immunoglobulin (SCIG) infusion.¹

The approval was based on findings from the randomized, double-blinded, placebo-controlled ADVANCE-CIDP 1 trial (NCT02549170) and the single-arm, open-label, extension ADVANCE-CIDP 3 study (NCT02955355) that assessed the efficacy and safety of Hyqvia in adults with CIDP. The analysis of the primary end point among 122 with CIDP from ADVANCE-CIDP 1 showed a statistical difference between the relapse rates in the Hyqvia group (n = 57; 14.0%) compared with the placebo group (n = 65; 32.3%), which was significant (P = .0314).^1,2

“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,” Giles Platford, president of Takeda’s Plasma-Derived Therapies Business Unit, said in a statement.¹ “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.”

The efficacy assessment on Hyqvia included adults with a confirmed diagnosis of CIDP and who had remained on a stable dosing regimen of intravenous immunoglobulin (IVIG) therapy for at least 3 months before screening. The treatment difference of -18.3% (2-sided 95% CI, -32.1% to -3.1%) indicated that Hyqvia displayed superiority over placebo in preventing relapse of CIDP.

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 effects (AEs) observed in at least 5% of study participants in the clinical trials of Hyqvia for CIDP included local reactions, headache, pyrexia, nausea, fatigue, erythema, pruritus, increased lipase, abdominal pain, back pain, and pain in extremity.

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Presented at the 2023 Peripheral Nerve Society (PNS) Annual Meeting in Copenhagen, Denmark, on June 20, 2023, data from ADVANCE-CIDP 1 also showed a lower probability of functional worsening rates with Hyqvia in comparison with placebo (37.5% vs 54.4%; 95% CI, ­–33.02 to 0.69).² Patients on active therapy experienced longer time to relapse compared with those on placebo, with Kaplan-Meier estimate curves separating early, at approximately week 4. Changes on Rasch-built Overall Disability Scale centile score, a secondary end point, also continued to favor the Hyqvia group (least squares mean difference, ­–6.1 [SD, 1.64] vs –0.9 [SD, 1.69], respectively).

From the analysis presented at the meeting, the safety profile of Hyqvia was generally consistent with the existing EU Summary of Product Characteristics, with the most common casually-related local AEs being injection and infusion site pain and erythema, and infusion site edema and pruritis. The most common causally-related systemic AEs included headache, nausea, fatigue, and pruritus. Throughout the trial, the majority (88.7%) of patients receiving active drug were on a 4-week dosing interval with a mean time to deliver treatment of 125.9 minutes. The majority (86.3%) of patients received study treatment using 2 infusion sites per treatment, while 9.6% and 3.7% used 1 and 3 infusion sites, respectively.

The company noted that patients with CIDP can infuse Hyqvia up to once monthly (every 2, 3, or 4 weeks) because of the hyaluronidase component, which can facilitate the dispersion and absorption of large IG volumes in the subcutaneous space between the skin and the muscle. Since the treatment is delivered subcutaneously, Hyqvia can be administered by a healthcare professional in a medical office, infusion center, or at a patient’s home. Additionally, the treatment can be self-administered by the patient or caregiver after appropriate training.

“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,” Lisa Butler, the executive director of GBS-CIDP Foundation International, said in a statement.¹ “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.”

In 2014, Hyqvia first received approval in the United Syayes for the treatment of adults with primary immunodeficiency, which has since expanded to include children between 2 and 16 years old. In December 2023, the European Medicines Agency’s Committee for Medicinal Products for Human Use recommended the approval of Hyqvia as maintenance therapy in patients with CIDP after stabilization with intravenous IG. The company noted that the European Commission will consider the positive recommendation when determining the potential marketing authorization for treatment for CIDP throughout the European Union.¹

The approval marks a major step forward for the CIDP treatment paradigm, which has long sought a novel therapy. In a recent NeurologyLive Insights series, Richard Lewis, MD, discussed this at length while reviewing the current therapeutic pipeline for the condition. He described the various investigational therapies that are under development with the potential to change the current treatment landscape of CIDP, including a number that could make their way into the physician arsenal in the coming years. Watch Lewis discuss the landscape in the below video.

REFERENCES
1. U.S. FDA Approves Takeda’s HYQVIA® as Maintenance Therapy in Adults with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). News Release. Takeda. Published January 16, 2024. Accessed January 16, 2024. https://www.takeda.com/en-us/newsroom/news-releases/2024/us-fda-approves-takedas-hyqvia-as-maintenance-therapy-in-adults-with-chronic-inflammatory-demyelinating-polyneuropathy-cidp
2. Takeda presents full data set from phase 3 ADVANCE-CIDP 1 clinical trial investigating Hyqvia as a maintenance therapy for chronic inflammatory demyelinating polyneuropathy at PNS Annual Meeting. News release. June 20, 2023. Accessed July 5, 2023. https://www.takeda.com/en-us/newsroom/news-releases/2023/takeda-presents-full-data-set-from-phase-3-ADVANCE-CIDP-1-clinical-trial-investigating-HYQVIA%C2%AE-as-a-maintenance-therapy-for-chronic-inflammatory-demyelinating-polyneuropathy-CIDP-at-PNS-annual-meeting/