Following the approval of Takeda's Hyqvia, the FDA has approved the company's immune globulin (IG) infusion 10% (human) (Gammagard Liquid) as an intravenous immunoglobulin (IVIG) therapy to improve neuromuscular disability and impairment in adults with chronic inflammatory demyelinating polyneuropathy (CIDP).1
The approval is based on results from the prospective, open-label, single-arm, multicenter ADVANCE-CIDP 2 trial (NCT02549170) which comprised of adults with CIDP who developed a relapse in the previously-completed, placebo-controlled ADVANCE-CIDP 1 trial (NCT02549170) evaluating efficacy, safety and tolerability of Hyqvia. Among 18 patients with CIDP in the trial, findings showed a 94.4% responder rate (95% CI, 74.2% to 99.0%), suggesting an improvement in functional disability.
Top Clinical Takeaways
- The FDA's approval of Takeda's Gammagard Liquid marks a significant advancement in chronic inflammatory demyelinating polyneuropathy (CIDP) treatment options for adults.
- Recognized as the standard of care, intravenous immunoglobulin (IVIG) therapy, such as Gammagard Liquid, is designed to normalize compromised immune systems.
- With the recent approval of Hyqvia and Gammagard Liquid, Takeda provides clinicians with induction and maintenance therapy options, addressing the varied treatment needs of adults with CIDP.
“As the standard of care for the treatment of CIDP, IG therapy is thought to help normalize compromised immune systems through immunomodulatory mechanisms,” Mamatha Pasnoor, MD, professor in the Department of Neurology at the University of Kansas Medical Center, said in a statement.1 “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.”
READ MORE: FDA Approves Takeda’s Immune Globulin Infusion, Hyqvia, for Chronic Inflammatory Demyelinating Polyneuropathy
In ADVANCE-CIDP 2, Gammagard Liquid was administered to participants at an induction dose of 2 g/kg body weight, followed by maintenance infusions every 3 weeks for 6 months. The dosage could be adjusted at the discretion of the investigator but adjustments to the dosing interval of every 3 weeks were not allowed. Efficacy was based on responder rate, defined as at least a 2-point decrease in the adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score at the end of the treatment period.
At 6 months, 17 of the 18 patients (94.4%) demonstrated an INCAT score that returned to baseline values prior to joining the study. Overall, investigators observed that participants showed improvement in functional ability as defined by a composite outcome metrics that included INCAT score, grip strength, or Rasch-built Overall Disability Scale score. The most common adverse events reported in at least 5% of participants included 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.
“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 patients living with rare neuromuscular disorders and bringing our portfolio of differentiated IG therapies to these patients,” Richard Ascroft, JD, senior vice president and head of Takeda’s U.S. Plasma-Derived Therapies Business Unit, said in a statement.1 “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.”
Earlier this month, the FDA approved the company's Hyqvia, which is immune globulin (IG) infusion 10% (human) with recombinant human hyaluronidase, as maintenance therapy for adults CIDP to prevent relapse of neuromuscular disability and impairment. The approval was based on findings from ADVANCE-CIDP 1 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).2
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.
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).3 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 approval marks a major step forward for the CIDP treatment paradigm, which has long sought a novel therapy. In a recent interview with NeurologyLive®, Richard Lewis, MD, director of the electromyography laboratory and professor of neurology at Cedars-Sinai Medical Center, discussed how the approval marks a significant advancement in the field. He also talked about the advantages Hyqvia offers over traditional intravenous immunoglobulin treatments for patients with CIDP. Lewis, also a consultant for Takeda, spoke about how the potential shift to a 20% solution might impact the future of CIDP therapy and patient convenience.
REFERENCES
1. Takeda’s GAMMAGARD LIQUID® Approved by U.S. FDA for Adults with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). News Release. Takeda. Published January 29, 2024. Accessed January 29, 2024. https://www.takeda.com/newsroom/newsreleases/2024/Takedas-GAMMAGARD-LIQUID-Approved-for-Adults-with-CIDP-in-United-States/
2. 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
3. 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/
