Annexon Biosciences reported new Phase 3 data for its Guillain-Barré Syndrome (GBS) drug Tuesday morning, saying the low dose achieved the trial’s primary endpoint.
The company has a lot riding on the readout, with analysts forecasting stock swings of potentially more than 100% in a success and a fall of about 50% in case of failure. Investors keenly noted a late afternoon press release Monday announcing a conference call to discuss the data for Tuesday morning, sending shares $ANNX up as much as 50% after hours. (It closed at $4.58 on Monday.)
Tuesday’s data, from a program called ANX005, induced a 2.4-fold improvement on the GBS disability scale for patients taking the 30 mg/kg dosing regimen, good for a statistically significant result and p-value of p=0.0058. Researchers measured the improvements at week eight for the primary endpoint.
The higher, 75 mg/kg dose only reached statistical significance for patients with the most severe disease, defined as those who need ventilators, CEO Doug Love told Endpoints News. On the primary endpoint, that dose’s p-value came in at p=0.5548.
Jefferies analyst Andrew Tsai wrote in a note last month that ANX005 would need to generate an improvement of at least two-fold in order for the Phase 3 study to reproduce early-stage data.
Annexon IPO’ed at a $17 share price during the summer 2020 pandemic boom, but its stock has hovered between $2 and $8 per share since early 2022 in the wake of investor disappointment in trials for Huntington’s disease and geographic atrophy.
Lower dose, shorter duration
ANX005 is designed to block the activity of C1q, believed to set off a powerful inflammation cascade through the classical complement pathway. Love said the lack of a dose response stemmed from the lower dose remaining in patients’ nervous systems for less time — roughly one week — which allowed the body time and space to repair injured nerve cells.
The higher dose, meanwhile, tamped down on inflammation for longer, preventing such cleanup of damaged tissue except in only the sickest patients.
“What we see in our data is that shorter is better,” Love said. “Just blocking complement during the disease-process phase, for one week, is far superior than blocking complement during the disease-process phase and the recovery phase.”
Love added that the low dose showed statistical significance at all stages of disease severity, and the company will push for approval here. But Annexon may opt to ask the FDA to include the higher dose in a potential label to give physicians another option to treat very sick patients if necessary.
Guillain-Barré Syndrome is a rare disorder in which the body’s immune system attacks its nerves. Onset of the disease typically starts with weakness in patients’ extremities and can eventually lead to full paralysis if left untreated, according to the Mayo Clinic.
Though the cause isn’t known, cases sometimes arise after respiratory or gastrointestinal infections, including from the SARS-CoV-2 and Zika viruses. Annexon estimates about 22,000 people in the US and Europe are hospitalized from GBS each year.
In addition to the Phase 3 study, TD Cowen analyst Phil Nadeau said the program will also have to deliver positive real-world evidence in Western individuals, due to the pivotal trial enrolling patients solely from Bangladesh and the Philippines. Those data are expected in the first half of 2025, and Annexon plans to file for approval within that time frame too.
Love said Annexon ran its trial in southeastern Asia because the standard of care for GBS — intravenous immunoglobulin, or IVIg — is not FDA-approved, and regulators wanted a placebo-controlled study. He added there is a 2,000-patient natural history study that will help inform how the results translate to other demographics.
“When Annexon came forward, we could not run a study versus IVIg and get a label because [the FDA] didn’t know IVIg’s treatment effect,” Love said. “It would have been unethical to withhold it until you prove that therapeutic benefit with your drug.”
In addition to the efficacy results, Annexon said it didn’t observe any immune-related side effects, drug-related deaths or serious infections.