Annexon’s monoclonal antibody ANX005 reduced disability in patients with the rare autoimmune disorder Guillain-Barré syndrome (GBS), meeting the main goal of a phase 3 trial.
ANX005 also met a clutch of key secondary endpoints including improvements in muscle strength at day eight and reducing the number of days on artificial ventilation through week 26, according to a Tuesday morning press release.
The results sent Annexon’s shares soaring more than 37% in pre-market trading on Tuesday to $6.32 compared to $4.58 at close the day before.
The primary endpoint of the study was an improvement in GBS disability at week eight. ANX005 achieved a 2.4-fold improvement on this goal with the 30 mg/kg dose. The therapy also showed a 31-day reduction in median time to walk independently as compared to placebo.
Annexon said that patients who received ANX005 “got better sooner” on each of the secondary endpoints. The company also noted an early reduction in a key biomarker of nerve damage called neurofilament light chain.
GBS is a rare disorder that causes the body’s immune system to attack the nerves. It causes weakness and tingling in the hands and feet initially, which can eventually progress to total body paralysis. Most people recover from GBS, but it can be fatal. There are no curative treatments for the disorder, but medications can ease the symptoms and duration.
“These data represent an important moment for the GBS community and Annexon,” said Annexon CEO Douglas Love in a statement. “With the potential to be the first targeted treatment for GBS in the U.S., ANX005 demonstrated consistent improvement and functional benefits on key primary and secondary endpoints.”
Love noted that ANX005 resulted in rapid neuroprotection that stopped the advancement of the disease.
Annexon is developing ANX005 under the theory that inhibiting C1q in the complement cascade can stop the progression of neuroinflammation.
The phase 3 trial enrolled 241 patients in Bangladesh and the Philippines who received one of two doses of ANX005, either 30 mg/kg or 75 mg/kg. The higher dose was not statistically significant on the primary endpoint but did outperform placebo on some of the secondary goals, Annexon said.
Both doses achieved C1q inhibition but for different durations. The lower dose suppressed the marker for one week while the higher dose lasted for two to three weeks.
That taught Annexon that the 30-mg/kg dose has achieved the optimal treatment window because GBS causes tissue damage in the early stages of the disease.
“This well-designed, rigorous Phase 3 study demonstrated that acute and early intervention with ANX005 can deliver clinical benefits across the entire GBS disease spectrum,” said David Cornblath, M.D., professor emeritus of neurology at the Johns Hopkins University School of Medicine, in a statement.
ANX005 was well tolerated with no new safety signals raised in the late-stage test. The majority of adverse events were grade 1 and 2, including infusion-related reactions that occurred in 30% of patients.
Annexon plans to file a biologics license application with the FDA in the first half of 2025. Further data from the phase 3 test will be presented at the Peripheral Nerve Society Annual Meeting later this month.
ANX005 is also being developed in Huntington's disease and amyotrophic lateral sclerosis in phase 2.