Say Hy to proven relapse prevention as a maintenance therapy in adults

IG=Immune Globulin (Human), 10%; Hy=Recombinant Human Hyaluronidase

Study designs

ADVANCE-1¹

ADVANCE-1 (Study 1) was a phase 3, prospective, randomized, double-blind, multicenter, placebo-controlled study to investigate HyQvia as a maintenance therapy to prevent relapse of CIDP. Adults with definite/probable CIDP, an INCAT disability score of 0-7 (inclusive), and who were on a stable dose of IVIG for ≥12 weeks before screening were randomized and transitioned to HyQvia (n=62) or placebo (n=70).

The starting dose and dosing frequency was the same as the subject’s previous IVIG treatment
The mean monthly equivalent dose was 1.1 g/kg. Median duration of exposure was 5.3 months in the HyQvia group and 4.7 months in the placebo group
Relapse was defined as worsening of functional disability characterized by an increase of ≥1 point relative to baseline in adjusted INCAT disability score performed at two timepoints <7 days apart. Primary efficacy analyses were conducted in the modified intention-to-treat set (all randomized patients who received any double-blind medication) and compared relapse rates using a continuity-corrected X² test conducted at the 5% level of statistical significance

>90% (86*/94) of patients who completed ADVANCE-1 without CIDP worsening or relapse chose to enroll in ADVANCE-3²

*A total of 86 patients were enrolled in ADVANCE-3. One patient was subsequently excluded for not meeting all eligibility criteria, resulting in 85 patients included in the study population. Out of the 85 patients in the final ADVANCE-3 analysis, 43 were from the patient group previously infused with HyQvia and 42 were from the placebo group now infusing with HyQvia.³

ADVANCE-3^1-3

ADVANCE-3 (Study 2) was a phase 3b, single-arm, open-label, multicenter extension of ADVANCE-1 to assess long-term safety, tolerability, and immunogenicity of HyQvia for maintenance therapy for CIDP. It followed subjects who completed ADVANCE-1 without CIDP worsening or relapse.

The dosing range was 0.4 g/kg to 2.4 g/kg, given in a frequency of 2-, 3-, or 4-week intervals
All subjects entering ADVANCE-3^† continued to receive at the same dose and dosing interval as their full dose received in ADVANCE-1
Placebo-treated subjects who did not have worsened CIDP during Study 1 were identified when the data were unblinded, and they were discontinued following unblinding of ADVANCE-1 treatment allocation
An interim analysis, dated October 24, 2022, was performed. The data included 79 subjects with a range of follow-ups from 0 to 5.1 years and a total follow-up of 169 patient-years. A total of 2590 HyQvia infusions were administered
A final analysis, last subject completed July 03, 2023, presenting results of the full study, inclusive of data previously reported in the interim analysis, included 78 subjects with a range of follow-ups from 0 to 6.4 years (median 33 months) and a total follow-up of 200.691 patient-years. A total of 3487 HyQvia infusions were administered

CIDP=chronic inflammatory demyelinating polyneuropathy; INCAT=Inflammatory Neuropathy Cause and Treatment; IVIG=intravenous immune globulin.

^†Patients from the HyQvia arm of the ADVANCE-1 study continued the same dose regimen.³

Proven relapse* prevention¹

ADVANCE-1¹

PRIMARY ENDPOINT

Patients received treatments for 6 months or until relapse/withdrawal.

ADVANCE-1

Primary endpoint of ADVANCE-1 was met

Single-arm, open-label extension data, up to 6+ years²

No definitive conclusions or statistical claims can be drawn from the data below

ADVANCE-3 INTERIM EXPLORATORY ENDPOINT¹

8.8%

(n=5/57) of patients experienced relapse at the time of interim analysis (n=57; range: 0-5.1 years).

ADVANCE-3 FINAL EXPLORATORY ENDPOINT³

14.3%

(n=10/70) of patients experienced relapse in the final ADVANCE-3 open-label extension (n=70; median: 2.75 years, range: 0-6.4 years).

Endpoints from ADVANCE-3, a single-arm open-label extension safety study, were assessed as exploratory data. The study included patients from both the HyQvia and placebo arms of the ADVANCE-1 trial. Different treatment exposures may have influenced outcomes. No definitive conclusions or statistical claims can be drawn from the data above.

ADJUSTED INCAT

Adjusted INCAT score

The adjusted INCAT disability scores were identical to INCAT disability scores (scored 0-10, consists of the sum of the upper and lower limb scores, with higher values indicated increasing inability to make purposeful movements), with the exception that upper extremity score changes from 0 to 1 (normal to minor symptoms) or from 1 to 0 were excluded.⁴

CI=confidence interval.

*Relapse was defined as an increase of ≥1 point relative to the pre-subcutaneous treatment baseline score in 2 consecutive adjusted INCAT disability scores obtained <7 days apart. Primary efficacy analyses were conducted in the modified intention-to-treat set (all randomized patients who received any double-blind medication) and compared relapse rates using a continuity-corrected X² test conducted at the 5% level of statistical significance.^1,4

Review safety information

Safety Information, including contraindications and other specific warnings and precautions to consider when prescribing and monitoring patients treated with HyQvia.

SEE SAFETY INFORMATION

Time to relapse* data for HyQvia in CIDP

No definitive conclusions or statistical claims can be drawn from the data below

ADVANCE-1¹

SECONDARY ENDPOINT

ADVANCE-1 was a
randomized, placebo-
controlled study.
Prespecified endpoint analyses were not
controlled for multiplicity.

ADVANCE-3 FINAL EXPLORATORY ENDPOINT³

Of those who relapsed in ADVANCE-3, the mean (SD) time to relapse was 939.8 (566.0) days (n=70).

It was not possible to estimate the median time to relapse for subjects because the censoring rate was very high and fewer than 50% of subjects relapsed.

SD=standard deviation.

*Time to relapse was calculated as: Date of relapse – date of initial dose of treatment + 1. Patients who did not relapse were censored with time to censoring calculated as:

Date of discontinuation or completion – date of initial treatment + 1.^3,4

R-ODS* data for HyQvia in CIDP (activities of daily living)¹

No definitive conclusions or statistical claims can be drawn from the data below

ADVANCE-1^1,5†

SECONDARY ENDPOINT

-1.2

HyQvia (n=57)

Baseline - mean (SD)^‡: 63.5 (19.26) 

End of study - mean (SD)^§: 62.4 (20.12)

LS mean treatment
difference: 5:1

-6.3

Placebo (n=64)

Baseline - mean (SD)^‡: 57.3 (15.44) 

End of study - mean (SD)^§: 51.9 (18.11)

ADVANCE-1 was a randomized, placebo-controlled study. Prespecified endpoint analyses were not controlled for multiplicity.

ADVANCE-3 FINAL EXPLORATORY ENDPOINT³

+0.7 mean change from baseline^II (62.1) in R-ODS score to final^¶ ADVANCE-3 open-label extension (63.0) (n=70; SDs: 17.79 and 18.16, respectively).

ANCOVA=analysis of covariance; LS=least squares; R-ODS=Rasch-built Overall Disability Scale; SD=standard deviation

*The R-ODS score, used to assess activities of daily living, was a centile metric with lower scores reflecting more severe limitations. LS mean is from an ANCOVA model with the last non-missing change from pre-SC baseline in
R-ODS total score as the outcome, treatment group and baseline R-ODS total score as a covariate.⁵

^†Modified intent-to-treat analysis set includes all randomized subjects who received any double-blind investigational product.⁵

^‡Baseline value is defined as the pre-SC treatment baseline visit value, if non-missing. If missing, then the screening visit value is used (if non-missing).⁵

^§Study termination timepoint is defined as last non-missing post baseline record.⁵

^IIBaseline value is defined as grip strength assessment at end of study visit in ADVANCE-1 with non-missing values. If no value is available from the baseline visit, then the most recent non-missing measurement prior to first dose of HyQvia in ADVANCE-3 and after last HyQvia dose in ADVANCE-1 is used.³

^¶Study termination timepoint includes the last assessment performed on or after the end of treatment visit.³

**Grip strength* data overview^3,6**

No definitive conclusions or statistical claims can be drawn from the data below

ADVANCE-1 PRESPECIFIED EXPLORATORY ENDPOINT^6†

Mean change from baseline in maximum hand grip strength of the more affected hand:

+5.9 kPa

mean change in grip strength from baseline^‡ (55.4, n=57) to end of study^§ (62.0, n=55) with HyQvia

+2.0 kPa

mean change in grip strength from baseline^‡ (54.5, n=64) to end of study^§ (56.5, n=64) with placebo

There is no statistically significant difference between the two groups.

ADVANCE-1 was a randomized, placebo-controlled study. Prespecified endpoint analyses were not controlled for multiplicity, therefore no definitive conclusions or statistical claims can be drawn from this data.

ADVANCE-3 FINAL EXPLORATORY ENDPOINT³

Mean change from baseline in maximum hand grip strength of the more affected hand:

-2.5 kPa

mean change in grip strength from baseline^II (66.5, n=78) to end of study^¶ (61.8, n=64) with HyQvia

kPa=kilopascal

*Hand grip strength was assessed using a Vigorimeter and a maximum of three measurements per hand were taken at each study visit.^3,6

^†Modified intent-to-treat analysis set includes all randomized subjects who received any double-blind investigational product.⁶

^‡Baseline value is defined as the pre-SC treatment baseline visit value, if non-missing. If missing, then the screening visit value is used (if non-missing).⁶

^§Study termination timepoint is defined as last non-missing post baseline record.⁶

^¶Study termination timepoint includes the last assessment performed on or after the end of treatment visit.³

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Review Safety

IMPORTANT SAFETY INFORMATION including BOXED WARNING for Thrombosis

INDICATION

HyQvia is indicated for the treatment of 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

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 after treatment with IG products, including HyQvia, 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): 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 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.

Transmissible 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 clinical trials in >5% of patients were: 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.

INDICATION

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

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.

Spread of Localized Infection: Do not infuse HyQvia into or around an infected area due to potential risk of spreading a localized infection.

Transmissible Infectious Agents: Because HyQvia is made from human plasma, there is a risk of transmitting infectious agents (e.g. viruses, other pathogens).

Adverse Reactions

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

Please click for Full Prescribing Information.

References

HyQvia. Prescribing information. Takeda Pharmaceuticals U.S.A., Inc.; 2025.
Hadden RDM, Andersen H, Bril V, et al. Long-term safety and tolerability of hyaluronidase-facilitated subcutaneous immunoglobulin 10% as maintenance therapy for chronic inflammatory demyelinating polyradiculoneuropathy: Results from the ADVANCE-CIDP 3 trial. J Peripher Nerv Syst. 2024;29(4):441-452. doi:10.1111/jns.12672.
ADVANCE-3 Data on File.
Bril V, Hadden RDM, Brannagan TH 3rd, et al. Hyaluronidase-facilitated subcutaneous immunoglobulin 10% as maintenance therapy for chronic inflammatory demyelinating polyradiculoneuropathy: The ADVANCE-CIDP 1 randomized controlled trial. J Peripher Nerv Syst. 2023;28(3):436-449. doi:10.1111/jns.12573.
HyQvia Data on File. CIDP ADVANCE-1 R-ODS Baseline and End of Treatment Data Exclude 1 Site.
ADVANCE-1 Data on File.

Say Hy to proven relapse prevention as a maintenance therapy in adults

Patients Experiencing Relapse

Time to Relapse

Activities of Daily Living

Grip Strength

Grip strength* data overview3,6

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**Grip strength* data overview^3,6**