The Food and Administration (FDA) has approved Rystiggo^® (rozanolixizumab-noli) for the treatment of generalized myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive.

Rystiggo is a humanized monoclonal antibody that binds with high affinity to human neonatal Fc receptor (FcRn) resulting in the reduction of circulating immunoglobulin G (IgG). The approval was based on data from the phase 3 MycarinG study (ClinicalTrials.gov Identifier: NCT03971422), which included 200 adults with gMG.

Patients were randomly assigned 1:1:1 to receive weekly rozanolixizumab 7mg/kg, rozanolixizumab 10mg/kg, or placebo subcutaneously for 6 weeks, followed by an 8-week observation period.

Results showed that treatment with rozanolixizumab met the primary endpoint demonstrating a significant improvement in the Myasthenia Gravis-Activities of Daily Living total score at day 43, with a least square mean difference vs placebo of -2.6 points at both the 7mg/kg dose and 10mg/kg dose (both doses P <.001).

Additionally, a statistically significant difference in the Quantitative Myasthenia Gravis total score at day 43 (key secondary endpoint) was observed with rozanolixizumab, with a least square mean difference vs placebo of -3.5 points at the 7mg/kg dose and -4.8 points at the 10mg/kg dose (both doses P <.001).

The most common adverse reactions reported with rozanolixizumab were headache, infections, diarrhea, pyrexia, hypersensitivity reactions, and nausea.

Rystiggo is supplied in a 280mg/2mL single-dose vial. It is administered subcutaneously using an infusion pump. The product is expected to be available in the third quarter of 2023.

The ADAPT-SC open label trial (ClinicalTrials.gov Identifier: NCT04735432) was conducted to compare the safety and efficacy of subcutaneous vs multiple infusions of efgartigimod coformulated with PH20 in patients with generalized MG.

For the current study, researchers assessed the safety and efficacy of efgartigimod in patients with anti-acetylcholine receptor antibody-negative (AChR-Ab-) generalized MG in the ADAPT-SC study population.

The researchers included patients with MG from the ADAPT-SC study who received at least 1 dose of subcutaneous efgartigimod PH20 and were AChR-Ab- in the analysis.

Of 164 patients who received efgartigimod in the ADAPT-SC study, 30 were AChR-Ab-. Median follow-up was 204 days.

Patients with MG who were AChR-Ab- showed improvements from study baseline in scores of activities of daily living and quality of life (-3.6±0.53 and -3.3±0.80, respectively) at week 4. The results were consistent with those observed among AChR-Ab+ patients (-4.1±0.29 and -5.2±0.47, respectively).

With regard to safety of efgartigimod, 76.2% of study participants had 1 or more mild/moderate adverse events, including injection site erythema, headache, and COVID-19. None of the adverse events led to study discontinuation.

The researchers concluded, “Long-term treatment with efgartigimod PH20 SC [subcutaneous] was associated with consistent and repeatable improvements in MG-ADL [activities of daily living and quality of life] scores in AChR-Ab- patients in ADAPT-SC+ and was well tolerated.”

Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the authors’ disclosures.

The Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) for rozanolixizumab for the treatment of adults with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive.

Rozanolixizumab is a humanized monoclonal antibody that binds with high affinity to human neonatal Fc receptor (FcRn). The investigational treatment is designed to block the interaction of FcRn and immunoglobulin G (IgG), accelerating the catabolism of antibodies and inducing the removal of pathogenic IgG autoantibodies. 

The BLA is supported by data from the phase 3 MycarinG study (ClinicalTrials.gov Identifier: NCT03971422), which enrolled 200 adult patients with gMG. Patients were randomly assigned 1:1:1 to receive weekly rozanolixizumab 7mg/kg, rozanolixizumab 10mg/kg, or placebo subcutaneously for 6 weeks, followed by an 8-week observation period.

Results showed that treatment with rozanolixizumab led to significant improvement in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score at day 43, with a least square mean difference vs placebo of -2.59 points at the 7mg/kg dose and -2.62 points at the 10mg/kg dose (both doses P <.001). 

Additionally, compared with placebo, a greater proportion of patients treated with rozanolixizumab 7mg/kg and 10mg/kg achieved clinically meaningful reductions in key secondary endpoints, including a 2.0-point or greater improvement in MG-ADL (P <.001), a 3.0-point or greater improvement in Quantitative Myasthenia Gravis (QMG) scores and a 3.0-point or greater improvement in Myasthenia Gravis Composite (MGC) scores.

As for safety, the most frequently reported treatment-emergent adverse events (TEAEs) with rozanolixizumab were headache, diarrhea, pyrexia, and nausea, with most cases being mild to moderate in severity.

The Company expects to receive feedback from the FDA in the second quarter of 2023.

Reference

UCB announces rozanolixizumab BLA for the treatment of generalized myasthenia gravis filed with US FDA and designated for Priority Review. News release. UCB. Accessed January 6, 2023. https://www.prnewswire.com/news-releases/ucb-announces-rozanolixizumab-bla-for-the-treatment-of-generalized-myasthenia-gravis-filed-with-us-fda-and-designated-for-priority-review-301714932.html.

Rystiggo^® (rozanolixizumab-noli) is now available for the treatment of generalized myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive.

Rystiggo is a humanized monoclonal antibody that binds with high affinity to human neonatal Fc receptor resulting in the reduction of circulating immunoglobulin G. The approval was based on data from the phase 3 MycarinG study (ClinicalTrials.gov Identifier: NCT03971422).

The treatment is supplied in a 280mg/2mL single-dose vial. It is administered subcutaneously by a health care provider using an infusion pump. Treatment can be administered at multiple care sites including physicians’ offices, hospital outpatient clinics, and independent infusion centers. Additionally, for patients who are eligible, UCB has partnered with a limited network of specialty pharmacies with home infusion capabilities.

To provide support to patients and caregivers, UCB has established the ONWARD patient support program.  Health care providers can enroll their patients in the program using the Rystiggo Start Form.

“Now that Rystiggo is FDA-approved and commercially available, we are committed to advancing access to the care and support journey of eligible patients. This is so important because we know there is a high unmet need for personalized rare disease support,” said Kimberly Moran, PhD, Head of US Rare Diseases, UCB. “That’s why we co-created ONWARD with the help of patients and health care providers from the myasthenia gravis community to help them manage living with this rare disease.”

The Food and Drug Administration (FDA) has approved Vyvgart^® Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.

Vyvgart Hytrulo is a combination of efgartigimod alfa, a neonatal Fc receptor blocker, and hyaluronidase, an endoglycosidase. Hyaluronidase increases permeability of the subcutaneous (SC) issue allowing for SC injection of the biologic product.

The approval was based on data from the randomized, open-label, parallel-group phase 3 ADAPT-SC study (ClinicalTrials.gov Identifier: NCT04735432), which compared the efficacy and safety of SC efgartigimod to IV efgartigimod (Vyvgart) in adults with gMG.

Results showed that treatment with SC efgartigimod was noninferior to IV efgartigimod (primary endpoint; P <.0001). At day 29, the mean total IgG reduction was 66.4% and 62.2% in the SC efgartigimod and IV efgartigimod groups, respectively.

“The clinical trials of Vyvgart continue to show significant benefit to patients with a favorable safety profile and clear improvements in gMG disease scores,” said James F. Howard Jr, MD, Professor of Neurology (Neuromuscular Disease), Medicine and Allied Health, Department of Neurology, The University of North Carolina at Chapel Hill School of Medicine and Principal Investigator for the ADAPT-SC trial. “Now with the approval of Vyvgart Hytrulo, we have a broad gMG treatment offering with both IV and SC administration options and can select based on patient needs and preference without sacrificing clinical benefit or safety.”

Vyvgart Hytrulo is administered subcutaneously only by a health care professional using a winged infusion set. The product is supplied as a solution containing 1008mg efgartigimod alfa and 11,200 units hyaluronidase per 5.6mL in a single-dose vial. It is expected to be available in July 2023.

Researchers conducted a Bayesian network meta-analysis to compare the newer treatments for generalized MG in terms of HRQoL outcomes.

The researchers analyzed published data from 4 randomized placebo-controlled phase 3 trials. To assess outcomes, the researchers used changes in HRQoL outcomes, European QOL 5 Dimensions visual analog scale (EQ-5D VAS), and MG QOL revised (MG-QoL 15r) questionnaires.

Findings of the meta-analysis showed that treatment with efgartigimod vs ravulizumab resulted in improved EQ-5D VAS (mean difference, 10.39; 95% credible interval [Crl], 2.39-18.31) and MG-QoL 15r scores (-3.29; 95% Crl, -6.01 to -0.61).

Efgartigimod was also superior to zilucoplan on the EQ-5D VAS scale (8.50; 95% Crl, 0.66-16.48); however, improvements in MG-QoL 15r were not significantly different between the 2 treatments.

Improvements on the EQ-5D VAS and MG-QoL 15r scales were not significantly different between treatment with efgartigimod and rozanolixizumab 7 and 10 mg.

The researchers concluded, “The results suggested efgartigimod was associated with greater degree of improvement in EQ-5D VAS (compared to ravulizumab and zilucoplan) and MG-QoL15r (compared to ravulizumab) scores in patients with gMG [MG].”

The Food and Drug Administration (FDA) has approved Zilbrysq^® (zilucoplan) for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.

Zilbrysq is a macrocyclic peptide inhibitor of complement component 5 (C5), which binds to and inhibits the cleavage of C5 into C5a and C5b, preventing the generation of the terminal complement complex, C5b-9. Though the exact mechanism is unknown, it is believed that Zilbrysq exerts its therapeutic effect by reducing C5b-9 deposition at the neuromuscular junction.

The approval was based on data from the double-blind, placebo-controlled phase 3 RAISE study (ClinicalTrials.gov Identifier: NCT04115293), which included 174 adults with mild to severe anti-AChR-antibody positive gMG. Study participants (mean age, 53 years) were randomly assigned 1:1 to receive zilucoplan (n=86) or placebo (n=88) subcutaneously once daily for 12 weeks. 

The primary endpoint was the change from baseline to week 12 in the MG-Activities of Daily Living (MG-ADL) total score, which assesses the impact of gMG on daily functions of 8 signs/symptoms typically affected in gMG. At baseline, the mean MG-ADL total score was 10.6 (range: 6-19). Efficacy was also measured using the Quantitative Myasthenia Gravis (QMG) total score, which assesses muscle weakness. For both measures, higher scores indicate more impairment.

Treatment with zilucoplan was associated with statistically significant improvements in both MG-ADL total score (difference from placebo, -2.09 [95% CI, -3.24, -0.95]) and QMG total score (difference from placebo, -2.94 [95% CI, -4.39, -1.49]) (both P <.001). Additionally, the proportion of patients with improvements of at least 3 and 5 points in the MG-ADL total score and QMG total score, respectively, was greater for zilucoplan (73.1% and 58%) compared with placebo (46.1% and 33%).

The most common adverse reactions reported with treatment were injection site reactions, upper respiratory tract infection, and diarrhea. The prescribing information for Zilbrysq includes a Boxed Warning regarding the risk of serious meningococcal infections that have occurred in patients treated with complement inhibitors. Because of this risk, Zilbrysq is only available through a restricted program called Zilbrysq REMS.

Zilbrysq is supplied as single-dose prefilled syringes in 16.6mg/0.416mL, 23mg/0.574mL, and 32.4mg/0.81mL dosage strengths. Prior to initiating treatment, baseline lipase and amylase levels should be obtained. Zilbrysq is administered as a once daily subcutaneous injection; dosage is dependent on actual body weight. Patients may self-inject Zilbrysq after receiving training from their health care provider.

The product is expected to be available by the end of this year.

The approval of Zilbrysq, a complement inhibitor, was based on data from the phase 3 RAISE study (ClinicalTrials.gov Identifier: NCT04115293), which included 174 adults with mild to severe anti-AChR-antibody positive gMG. Treatment with Zilbrysq was associated with statistically significant improvements in both the MG-Activities of Daily Living total score and the Quantitative Myasthenia Gravis total score. The most common adverse reactions reported with treatment were injection site reactions, upper respiratory tract infection, and diarrhea.

Zilbrysq is supplied as a single-dose prefilled syringe in 16.6mg/0.416mL, 23mg/0.574mL, and 32.4mg/0.81mL dosage strengths, and is available exclusively through PANTHERx^® Rare Pharmacy. UCB has established a support program called ONWARD that provides tools and resources for eligible patients and caregivers.

Prior to initiating treatment, baseline lipase and amylase levels should be obtained. Zilbrysq is administered as a once daily subcutaneous injection; dosage is dependent on actual body weight. Patients may self-inject Zilbrysq after receiving training from their health care provider.

Zilbrysq is contraindicated in patients with unresolved Neisseria meningitidis infection. Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. Because of this risk, Zilbrysq is only available through a restricted program called Zilbrysq REMS. Clinicians who wish to prescribe Zilbrysq must be certified in the REMS.