FDA Approves Efgartigimod Alfa and Hyaluronidase for CIDP

The FDA has approved efgartigimod alfa and hyaluronidase-qvfc (Vyvgart Hytrulo; Argenx) for the treatment of adult patients with chronic inflammatory demyelinating polyneuropathy (CIDP), Argenx announced in a press release today.¹

Efgartigimod alfa and hyaluronidase is the first neonatal Fc receptor (FcRn) blocker to be approved for CIDP, a rare and serious autoimmune condition typically treated with corticosteroids, immunoglobulin therapy, or plasma exchange in the first line.^1,2 It is now approved for CIDP as a once-weekly subcutaneous injection.¹

"This medication has a novel mechanism of action for the treatment of patients with CIDP. This approval is significant as it can provide additional options for patients for the treatment of this rare disease," Karissa Gable, MD, associate professor of neurology at Duke University and an investigator on the ADHERE trial, told The American Journal of Managed Care^®.

Efgartigimod alfa and hyaluronidase is now FDA approved for the treatment of adults with CIDP. | Image credit: wladimir1804 - stock.adobe.com

The supplemental biologics license application was accepted for priority review in February 2024,³ with the application and approval supported by data from the phase 2 ADHERE study (NCT04281472) assessing the safety, efficacy, and tolerability of efgartigimod alfa and hyaluronidase in adults with CIDP.^1,4 ADHERE is the largest clinical trial to date investigating CIDP treatment.¹

Results from ADHERE presented during a plenary session at this year’s American Academy of Neurology annual meeting, held April 13-18, 2024, found that patients with CIDP treated with efgartigimod coformulated with recombinant human hyaluronidase experienced clinical responses to treatment and went longer without relapse compared with patients in the placebo arm.⁵

The 2-part trial enrolled 322 patients with active disease in stage A, which was an open-label phase of weekly subcutaneous efgartigimod lasting up to 12 weeks. Those who responded entered stage B, a randomized-withdrawal phase comparing weekly efgartigimod with placebo for up to 48 weeks. A total of 221 patients were randomized and treated with either efgartigimod (n = 111) or placebo (n = 110) in stage B. In stage A, 214 participants (66.5%) were considered treatment responders (95% CI, 61.0%-71.6%).

The study’s main end points were evidence of clinical improvement in stage A and the efficacy of efgartigimod compared with placebo in part B. Efficacy was determined by time to clinical deterioration, which was defined as time to the first adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) score deterioration.

The risk of clinical deterioration, or relapse, was significantly lower among patients in stage B who continued treatment with efgartigimod vs those who received a placebo (HR, 0.394; 95% CI, 0.25-0.61; P = .000039). The risk of relapse was reduced among patients who had received a range of therapies, including corticosteroids, intravenous or subcutaneous immunoglobulin, or no treatment, ahead of participating in the study. Regarding measures of disease severity and progression, Inflammatory Rasch-built Overall Disability Scale score and grip strength showed similar features to INCAT scores.

Treatment-related adverse events were mild in the study, and although 3 deaths occurred, none were considered treatment-related deaths.

Clinical results in the ADHERE study also added to the understanding of CIDP’s underlying biology.³ Because the treatment is an FcRn blocker, its efficacy suggests IgG antibodies are a significant piece of the underlying biology of the disease.

CIDP is typically diagnosed in individuals aged 40 to 60 years, and approximately 24,000 patients in the US are undergoing CIDP treatment.¹ Affected patients experience progressive weakness and sensation loss in the upper and lower limbs, which impacts daily activities such as walking or standing up from a seated position.

Efgartigimod (Vyvgart) and efgartigimod alfa and hyaluronidase-qvfc are both FDA approved for the treatment of generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive.

"While most patients do respond to the first-line previously approved therapies, it is so important to have additional options such as this medication with a novel mechanism of action," Gable said. "Direct comparison is difficult to predict without a clinical trial that can provide that sort of data, however, the effectiveness of Vyvgart-hytrulo was demonstrated in this randomized double blinded placebo control trial."

References

1. Argenx announces FDA approval of Vyvgart Hytrulo for chronic inflammatory demyelinating polyneuropathy. News release. Argenx. June 21, 2024. Accessed June 21. 2024. https://www.us.argenx.com/news/argenx-announces-fda-approval-vyvgart-hytrulo-chronic-inflammatory-demyelinating-polyneuropathy

2. CIDP (chronic inflammatory demyelinating polyneuropathy). Cleveland Clinic. Updated December 4, 2023. Accessed June 20, 2024. https://my.clevelandclinic.org/health/diseases/cidp-chronic-inflammatory-demyelinating-polyneuropathy

3. Argenx announces FDA acceptance of supplemental biologics license application with priority review for Vyvgart Hytrulo in chronic inflammatory demyelinating polyneuropathy. News release. Argenx. February 20, 2024. Accessed June 20, 2024. https://www.us.argenx.com/news/argenx-announces-fda-acceptance-supplemental-biologics-license-application-priority-review

4. A study to assess the safety and efficacy of a subcutaneous formulation of efgartigimod in adults with chronic inflammatory demyelinating polyneuropathy (CIDP, an autoimmune disorder that affects the peripheral nerves) (ADHERE). ClinicalTrials.gov. Updated August 4, 2023. Accessed June 20, 2024. https://clinicaltrials.gov/study/NCT04281472

5. Efficacy, safety, and tolerability of efgartigimod in patients with chronic inflammatory demyelinating polyneuropathy: results from the ADHERE trial. Abstract presented at: American Academy of Neurology 2024 Annual Meeting; April 13-18, 2024; Denver, CO. Accessed June 20, 2024. https://www.neurology.org/doi/10.1212/WNL-.0000000000206324