VYVGART had a demonstrated safety profile in the ADAPT clinical trial1
Adverse reactions in ≥5% of patients treated with VYVGART for IV infusion and more frequently than placebo in ADAPT1
| Adverse reaction | VYVGART (n=84) | Placebo (n=83) |
|---|---|---|
| Respiratory tract infection | 33% | 29% |
| Headache* | 32% | 29% |
| Urinary tract infection | 10% | 5% |
| Paraesthesia† | 7% | 5% |
| Myalgia | 6% | 1% |
*Headache includes migraine and procedural headache.1
†Paraesthesia includes oral hypoesthesia, hypoesthesia, and hyperesthesia.1
A higher frequency of patients who received VYVGART for IV infusion compared to placebo was observed to have below normal levels of white blood cell counts (12% vs 5%), lymphocyte counts (28% vs 19%), and neutrophil counts (13% vs 6%).1
The majority of infections and hematologic abnormalities were mild to moderate in severity.1
In clinical trials, hypersensitivity reactions, including rash, angioedema, and dyspnea were observed in patients treated with VYVGART for IV infusion. Hypersensitivity reactions were mild or moderate, occurred within one hour to three weeks of administration, and did not lead to treatment discontinuation.1
Postmarketing experience with VYVGART for IV infusion included reports of anaphylaxis and hypotension leading to syncope, as well as infusion-related reactions including hypertension, chills, shivering, and thoracic, abdominal, and back pain. These reactions occurred during or within an hour of administration and led to infusion discontinuation and in some cases to permanent treatment discontinuation.1
IV=intravenous; OLE=open-label extension.
LONG-TERM INTERIM SAFETY DATA
NEW
As observed in anti–AChR-Ab positive patients, VYVGART for IV infusion showed a consistent and reliable safety profile across anti–AChR-Ab negative patients1*
In the ADAPT-SERON clinical trial:
- In ADAPT-SERON, the overall safety profile was consistent with the known safety profile of VYVGART for IV infusion in patients with gMG as observed in the ADAPT and ADAPT-SC pivotal trials, with the exception of nausea, which occurred in 7% of anti–AChR-Ab negative patients treated with VYVGART for IV infusion compared to 5% of patients who received placebo.1-3
*"Anti–AChR-Ab negative" refers to anti–MuSK-Ab positive, anti–LRP4-Ab positive, or triple seronegative.3
Triple seronegative=anti-AChR, anti-MuSK, and anti-LRP4 antibodies negative.1,2
AChR-Ab=acetylcholine receptor antibody; gMG=generalized myasthenia gravis; IV=intravenous;
LRP4-Ab=low-density lipoprotein receptor-related protein 4 antibody; MuSK-Ab=muscle-specific tyrosine kinase antibody.
A consistent safety profile in the ADAPT-SC clinical trial1,2
In ADAPT-SC, the overall safety profile of VYVGART Hytrulo, except for a higher rate of injection site reactions, was consistent with the proven safety profile of VYVGART for IV infusion1,2
In the ADAPT clinical trial, the most common adverse reactions for patients treated with VYVGART for IV infusion were respiratory tract infection, headache, and urinary tract infection. Additionally, a higher frequency of patients who received VYVGART for IV infusion compared with placebo was observed to have below normal levels of white blood cell counts, lymphocyte counts, and neutrophil counts.2
In ADAPT-SC, the overall safety profile of VYVGART Hytrulo was consistent with VYVGART for IV infusion in the ADAPT pivotal trial, except for a higher rate of injection site reactions, which occurred in 38% of patients receiving VYVGART Hytrulo. These were injection site rash, erythema, pruritus, bruising, pain, and urticaria.2
In ADAPT-SC and its open-label extension (n=168)2:
- Injection site reactions were mild to moderate in severity and did not lead to treatment discontinuation
- The majority of injection site reactions occurred within 24 hours after administration and resolved spontaneously
- Most injection site reactions occurred during the first treatment cycle, and the incidence of injection site reactions decreased with each subsequent cycle
In clinical trials, hypersensitivity reactions, including rash, angioedema, and dyspnea were observed in patients treated with VYVGART Hytrulo or VYVGART for IV infusion. Urticaria was also observed in patients treated with VYVGART Hytrulo. Hypersensitivity reactions were mild or moderate and occurred within one hour to three weeks of administration.1,2
VYVGART Hytrulo can cause anaphylaxis and hypotension leading to syncope, as well as infusion/injection-related reactions including hypertension, chills, shivering, and thoracic, abdominal, and back pain. These reactions occurred during or within an hour of administration with VYVGART for IV infusion and led to infusion discontinuation and in some cases to permanent treatment discontinuation. If a hypersensitivity reaction occurs with VYVGART Hytrulo, the healthcare professional should institute appropriate measures if needed or the patient should seek medical attention. If a severe infusion/injection-related reaction occurs with VYVGART Hytrulo, initiate appropriate therapy.1,2
IV=intravenous.
Pregnancy registry information1,2
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to VYVGART Hytrulo or VYVGART during pregnancy. Healthcare providers and patients may call 1-855-272-6524 or go to https://www.vyvgartpregnancy.com to enroll in or to obtain information about the registry.
OLE=open-label extension.
LONG-TERM INTERIM SAFETY DATA
The ADAPT-SC+ Phase 3, open-label extension study1,4-6
An up-to-4–year, multicenter, single-arm trial in 180 adult patients with gMG4,5
PRIMARY ENDPOINT
The long-term safety and tolerability of VYVGART Hytrulo in adult patients with gMG4*
SC treatment cycle†
(1 dose per week for 4 weeks)
VYVGART Hytrulo
1,008 mg efgartigimod alfa/11,200 units hyaluronidase
subcutaneous (SC) injection
Each cycle consists of:
- A treatment period with 4 weekly injections, with an evaluation before each injection
- Year 1 of ADAPT-SC+: A ≥28-day intertreatment period with evaluations 1 week after the last injection, and then every 3 weeks until the patient needed retreatment
- Year 2 of ADAPT-SC+ onward: A
≥28-day intertreatment period was recommended between cycles, but a subsequent treatment period could be administered ≥7 days after last administration at the discretion of the investigator
Select criteria for retreatment:
- Patient completed the previous treatment cycle
- Patient could have benefited from retreatment, according to the investigator’s judgment
- ≥28 days (year 1) or ≥7 days (year 2 onward) from the last dose of the previous treatment cycle
- Patients were not required to have a worsening MG-ADL total score to be eligible for subsequent cycles
Study limitations: ADAPT-SC+ was a single-arm, open-label extension trial, not randomized or placebo-controlled and used descriptive statistics only. The study was designed to measure long-term safety, not efficacy, and the exploratory data should not be directly compared with pivotal trials ADAPT-SC or ADAPT. This information should be considered when evaluating the clinical importance of this analysis.
*The majority of patients (n=142) were positive for anti-AChR antibodies.5
†Participants who were not in need of retreatment at study entry instead started with an intertreatment period.5
AChR=acetylcholine receptor; gMG=generalized myasthenia gravis; MG-ADL=Myasthenia Gravis Activities of Daily Living.
Long-term safety data from the ADAPT-SC+ trial5
- ISRs decreased over subsequent cycles (from 33.9% [n/N=61/180] in cycle 1 to 3.9% [n/N=2/51] in cycle 24 of the original protocol)5
- No ISRs were grade ≥3, serious, or led to treatment discontinuation5
- In the overall study population (N=180), 138 (76.7%) participants completed the study and 42 (23.3%) participants discontinued early, most commonly due to withdrawal of consent (n=14 [7.8%]), physician decision (n=6 [3.3%]), TEAE (n=5 [2.8%]), and lack of efficacy (n=5 [2.8%])5
*Event rate was calculated as number of events per total patient years of follow-up.5
†Fatal events (metastatic renal cell cancer, cardiac arrest, respiratory failure [n=2], and COVID-19/respiratory failure) were not related to VYVGART Hytrulo treatment, as determined by investigators.5
‡Treatment discontinuations were due to metastatic renal cell cancer (cycle 1, fatal), cardiac arrest (cycle 2, fatal), pulmonary mass (cycle 3), COVID-19/ respiratory failure (cycle 3, fatal), MG crisis (cycle 1), thymoma (cycle 4), metastatic rectal cancer (cycle 21 [amended cycle 8]), and Bowen's disease (cycle 16 [amended cycle 5]).5
§Most frequent TEAEs occurring in >10% of participants in the overall population.5
COVID-19=Coronavirus Disease 2019; ER=event rate; ISR=injection site reaction; MG=myasthenia gravis; SAE=serious adverse event; TEAE=treatment-emergent adverse event.
EXPLORATORY ANALYSIS
Mean change in observed MG-ADL total score sustained across
163 weeks of ongoing treatment2,5*
Mean change from baseline in observed MG-ADL total score as patients moved through multiple cycles of treatment with VYVGART Hytrulo based on clinical evaluation.2,5
Analysis limitations: This was a prespecified descriptive exploratory analysis not controlled for multiplicity and not powered. Data should not be directly compared to pivotal trials ADAPT-SC or ADAPT. Data should be interpreted with caution, and conclusions cannot be drawn.5
*Decline in participant numbers during the study was due to participants completing the study at varying times and participants discontinuing early.
AChR-Ab=acetylcholine receptor antibody; CMI=clinically meaningful improvement; gMG=generalized myasthenia gravis; MG-ADL=Myasthenia Gravis Activities of Daily Living; SE=standard error.
Pregnancy registry information1,2
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to VYVGART Hytrulo or VYVGART during pregnancy. Healthcare providers and patients may call 1-855-272-6524 or go to https://www.vyvgartpregnancy.com to enroll in or to obtain information about the registry.
IV=intravenous.
