Acelyrin, Inc. is reporting two major clinical updates this week: the release of new phase 2 findings and details on the design of its phase 3 program for lonigutamab, an investigational candidate for the treatment of thyroid eye disease (TED).
First, a rundown on Acelyrin.
As a Los Angeles, California-based, clinical-stage biopharma company developing a pipeline of immunology-based therapeutics, Acelyrin made headlines last August after announcing it would suspend any further investments and no longer focus on developing izokibep (IL-17Ai)—its long-held main therapeutic under clinical investigation for two autoimmune diseases and uveitis—despite promising new data.
- In regards to izokibep’s uveitis indication: Disappointing topline data from a phase 2b/3 trial further supported its discontinuation of internal investments.
Acelyrin’s new focus: Lonigutamab.
Explain what this is.
Lonigutamab is a subcutaneously-delivered, humanized anti-insulin-like growth factor-1 receptor (IGF-1R).
How it works: By binding to a distinct epitope that, ideally, results in internalization of the IGF-1 receptor within minutes.
Lonigutamab’s potential: Acelyrin noted that lonigutamab’s subcutaneous delivery mechanism may also potentially enable “longer-term, convenient dosing” that could “improve depth and durability of clinical response.”
Now this clinical data.
We’ll start with the ongoing multicenter, dose-ranging phase 2 trial.
- The design: Two cohorts (each with placebo vs lonigutamab; see here for info on loading doses and dosing regimens)
The findings: The company reported “clinically meaningful and competitive improvements across all manifestations of TED.” These included:
- Proptosis
- Clinical activity score (CAS)
- Diplopia
- Graves Ophthalmology-Quality of Life (GO-QoL) tool
And those improvements?
Acelyrin further reported the following:
- Significant proptosis responder rate was observed with a 50 mg loading dose and 25 mg weekly subcutaneous dose of lonigutamab
- Efficacy was achieved with lower levels of exposure than was seen in intravenous (IV)-administered anti-IGF-IR agents.
- No cases of hearing impairments, hyperglycemia, or menstrual disorders among TED patients (reported as of Jan. 6 at any dose level of lonigutamab).
How did this data compare to prior findings?
Pretty similarly … the company’s previous six-week proof-of-concept data was reported in March 2024, in which the phase 1/2 trial found that lonigutamab “demonstrated rapid improvements in proptosis and (CAS) at the first measurement—within three weeks after the first subcutaneous dose.”
In announcing the data, then-CEO Shao-Lee Lin stated that the data supported their hypothesis that “lonigutamab has the potential to optimize benefit-risk by enabling longer-term subcutaneous dosing to increase depth and durability of clinical response while attempting to limit safety liabilities by avoiding the high maximal concentrations resulting from IV administration, while maintaining optimal therapeutic levels.”
And with this latest data, new CEO Mina Kim noted: “Lonigutamab, with its unique mechanism of action, is the first subcutaneous anti-IGF-1R to have demonstrated robust efficacy in TED patients comparable to the IV administered standard of care.”
This definitely sounds promising … Now talk about this phase 3 program.
The two global, double-masked, placebo-controlled studies anticipated for its phase 3 LONGITUDE program include:
- LONGITUDINAL-1
- LONGITUDINAL-2
Each trial will evaluate the safety and efficacy of a lonigutamab delivered subcutaneously as a 100 mg loading dose followed by 50 mgs every two weeks.
- The participants: ~350 patients diagnosed with active and chronic TED
- LONGITUDINAL-1: At least 81 participants with active TED
- LONGITUDINAL-2: No minimum number of required active TED participants
- The setup: Participants randomized 2:1 to either lonigutamab or placebo arms (for the first 24 weeks)
- After 24 weeks: Through 52 weeks of treatment, patients to receive lonigutamab
- The intent: To (potentially) enable longer-term treatment
- After 24 weeks: Through 52 weeks of treatment, patients to receive lonigutamab
- The primary endpoint: Proptosis response rate at 24 weeks for active TED patients (LONGITUDINAL-1) and active / chronic TED patients (LONGITUDINAL-2)
- The secondary endpoints: CAS, diplopia, and GO-QoL at 24 weeks
And what is this program based on?
An end-of-phase 2 meeting Acelyrin held with the FDA in Q3 2024, in which the company “gained alignment” on the trials’ designs.
So when might new data be released?
Acelyrin anticipates initiating the LONGITUDINAL program in Q1 2025 and releasing topline data in the second half (H2) of 2026.