CIDP Efficacy and Safety
Proven in the largest trial of CIDP and further evaluated in an extension study
EAN/PNS guideline recommends tailoring SCIg dose according to individual treatment response19
Largest Study in CIDP (n=172)
See the study design of PATH and
the Open-Label Extension (OLE) to PATH5,14
PATH Pivotal Trial design: Data from a randomized, multicenter, double-blind, placebo-controlled, parallel-group, phase III study of 2 doses of weekly Hizentra versus placebo for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP)—the PATH Study. Subjects who relapsed during the postrandomized phase were to receive IVIg as a rescue medication within 1 week. CIDP relapse was defined as a ≥1-point increase in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) score compared with baseline.
OLE to PATH Study design: 48-week, open-label, prospective extension study to PATH. 82 patients were enrolled: 62 patients were started on 0.4 g/kg weekly infusion of Hizentra, and 20 patients were started on 0.2 g/kg weekly. If clinically stable, patients on 0.4 g/kg were switched to 0.2 g/kg after 24 weeks. Upon CIDP relapse on 0.2 g/kg dose, 0.4 g/kg was either initiated or reinitiated. CIDP relapse defined as a ≥1-point increase in adjusted inflammatory Neuropathy Cause and Treatment (INCAT) score compared with baseline. Enrollment into the extension study started in 2014, more than 2 years after the start of the PATH study. Most patients had a time gap between completion of PATH and entry into the extension study during which they were treated with IVIG.
In the PATH Study
Relapse or withdrawal was significantly reduced with Hizentra
Recommended dose is 0.2 g/kg body weight per week. Both Hizentra doses demonstrated superiority over placebo for the primary endpoint.
†CIDP relapse was defined as a ≥1-point increase in adjusted INCAT score compared with baseline.
‡ARR=absolute risk reduction compared to placebo.
In the PATH Study
Hizentra was proven to keep patients with CIDP relapse free5§
§Data shown only consider CIDP relapse based on the adjusted INCAT score (relapse sensitivity analysis). All patients who withdrew for reasons other than relapse were assumed not to have had a relapse. The percentage of patients in each group who relapsed during the postrandomized phase are as follows: placebo= 56%, 0.2 g/kg=33%, and 0.4 g/kg=19%.
||ARR=Absolute Risk Reduction in risk of relapse compared to placebo.
In the PATH Study
Hizentra maintained functional ability across multiple secondary endpoints†
Hizentra also demonstrated better R-ODS scores vs placebo5||
- Median change from baseline to last postdose observation was −3.0 points for the placebo group, −2.0 points for the 0.2 g/kg Hizentra group, and 0.0 for the 0.4 g/kg Hizentra group (p=0.0002 for all).¶
†Study design: Data from a randomized, multicenter, double-blind, placebo-controlled, parallel-group, phase III study of 2 doses of weekly Hizentra versus placebo for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP)—the PATH Study.
‡Statistically significant vs placebo at the last postdose observation. The MRC (Medical Research Council) sum score was assessed in the following 8 bilateral muscle pairs: shoulder abduction, elbow flexion, wrist extension, index finger abduction, hip flexion, knee extension, foot dorsiflexion, and great toe dorsiflexion. The INCAT score is a 10-point scale that covers the functionality of legs and arms. Grip strength was measured in both hands by the Martin Vigorimeter. Grip strength change was for dominant hand.
§Overall p-values are based on both Hizentra dosing groups compared to placebo.
||The Rasch-built Overall Disability Scale (R-ODS) measures a patient's ability to perform a wide range of activities ranging from easy tasks, like reading a book, eating, and brushing teeth, to more difficult tasks such as standing for extended periods of time or running. Exploratory endpoint.
¶The difference between the 0.2 g/kg Hizentra group and the placebo group was not significant.
In the PATH Study, patients stabilized on IVIg
Reported a 3.6-fold lower rate of systemic adverse reactions per infusion when switched to Hizentra†
93% of 4,225 total Hizentra infusions were free of any ARs.5
†Data represent systemic side effects reported during the 13-week single-arm restabilization phase compared to those reported in the 2 Hizentra groups during the 24-week postrandomized phase. However, there was no parallel group of subjects receiving placebo in the IVIg restabilization phase.
The exposure-adjusted rate of systemic adverse reactions in the IVIg restabilization period for subjects who were also randomized to receive Hizentra was 0.075 reactions per week relative to an exposure-adjusted rate of 0.052 reactions per week during treatment with Hizentra. The exposure-adjusted systemic adverse reaction rate for Hizentra was 31% lower than the corresponding rate for IGIV. However, this difference should be interpreted with caution, because there was no parallel group of subjects receiving placebo during the period of IVIg treatment.
The exposure-adjusted rate of systemic adverse reactions in the IVIg restabilization period for subjects who were also randomized to receive Hizentra was 0.075 reactions per week relative to an exposure-adjusted rate of 0.052 reactions per week during treatment with Hizentra. The exposure-adjusted systemic adverse reaction rate for Hizentra was 31% lower than the corresponding rate for IGIV. However, this difference should be interpreted with caution, because there was no parallel group of subjects receiving placebo during the period of IVIg treatment.
ARs occurring in ≥5% of subjects treated with Hizentra and at a higher frequency than placebo-treated subjects
| Placebo n=57 |
0.2 g/kg Hizentra n=57 |
0.4 g/kg Hizentra n=58 |
|
| Local Reactions‡ | 7.0% | 19.3% | 29.3% |
| Headache | 3.5% | 7.0% | 6.9% |
| Nasopharyngitis | 1.8% | 7.0% | 3.4% |
| Fatigue | 1.8% | 8.8% | 0.0% |
| Upper Respiratory Tract Infection | 3.5% | 5.3% | 3.4% |
| Fall | 0.0% | 5.3% | 1.7% |
| Back Pain | 1.8% | 5.3% | 1.7% |
| Arthralgia | 1.8% | 5.3% | 1.7% |
| Pain in Extremity | 0.0% | 1.8% | 5.2% |
‡Includes the following infusion-site reactions: erythema, swelling, pain, induration, warmth, hematoma, and pruritus.
Zero cases of thrombosis or hemolysis were observed in Hizentra patients in the PATH Study.5 Thrombosis or hemolysis may occur with Ig products, including Hizentra. For patients at risk of thrombosis, administer Hizentra at the minimum dose and infusion rate possible. Please see the boxed warning and section 5 of the full prescribing information for more details.
In the PATH Study
More than 7 of 10 CIDP patients on Hizentra did not report local reactions
- Local reactions were the most commonly reported ARs
- Reports of infusion-site reactions decreased in frequency over time
- No subject withdrew because of local reactions§
Mild = does not interfere with routine activities.
Moderate = interferes somewhat with routine activities.
Severe = impossible to perform routine activities.
Moderate = interferes somewhat with routine activities.
Severe = impossible to perform routine activities.
Adjustable Hizentra dosing regimen demonstrated protection against CIDP relapse in OLE study to PATH
Most patients remained relapse-free when on either dosing option, with the 0.4 g/kg dose showing a lower rate of relapse14*
- Of the 72 patients who received 0.4 g/kg at some time during the study, 90% remained relapse-free while on the 0.4 g/kg dose
- Of the 73 patients who received 0.2 g/kg at some time during the study, 52% remained relapse-free while on the 0.2 g/kg dose
- Approximately 68% of patients who completed the PATH study without relapse were able to remain relapse-free after dose reduction to 0.2 g/kg
- Statistical tests comparing relapse rates between the 2 doses were not conducted
*CIDP relapse was defined as a ≥1-point increase in adjusted INCAT score compared with baseline.
Most patients who relapsed on the low dose recovered after reinitiating on the high dose14
-
Of the 62 patients who started on 0.4 g/kg, 52 patients switched to the low dose at week 24
- 50% (26 of 52) of those patients relapsed on the low dose
- 92% (24 of 26) of those who relapsed recovered within 4 weeks after reinitiating on the high dose
Overall, safety findings in the extension study were consistent with those from the PATH study and the established safety profile for Hizentra
- The most common adverse reactions (ARs) reported during the extension study included local site reactions, infections, fatigue, back pain, headache, dizziness, and nausea
- 22% of patients (n=18) reported 40 location reactions; one patient reported three causally related severe local reactions
- The majority of ARs were mild (62%) or moderate (29%)
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