Annexon’s ANX005 Slows ALS Progression in Phase 2a Study

That’s according to preliminary data from eight patients taking part in a Phase 2a clinical study (NCT04569435), whose main goal is to test how safe and well-tolerated ANX005 is when given as an intravenous (into-the-vein) infusion for up to 22 weeks.

Recruitment of up to 24 patients is underway at a number of locations across the U.S. and Canada. Those interested in participating may contact the study’s coordinator at (650) 822–5500, or via email at [email protected].

Full study data are expected this year, the company said in a press release announcing the progress of its lead programs.

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The complement system is a set of more than 20 blood proteins that normally help fight off infections or other foreign invaders. However, when it becomes abnormally activated, this system can contribute to the abnormal inflammatory responses that drive ALS and many other serious diseases.

One of the main complement proteins, C1q, has been shown to help control the number of neuronal junctions, or synapses, through which nerve cells communicate. This protein drives the removal of excess synapses, leaving only strong synapses that form appropriate nerve circuits.

But in autoimmune and neurodegenerative diseases, this protein tends to be chronically active, leading to the unwanted removal of functioning synapses, and resulting in progressive nerve damage and loss.

ANX005 is an antibody-based medication designed to bind and block the activity of C1q, which is expected to keep synapses healthy and slow or halt neurodegeneration.

The antibody is being developed for a number neurodegenerative diseases, such as ALS, Guillain-Barré syndrome (GBS), Huntington’s disease (HD), and cold agglutinin disease (CAD). Clinical trials are ongoing in all these indications.

The ongoing ALS trial is investigating ANX005 in patients whose first symptoms of weakness began in the past three years. Participants will receive two induction doses about 5–6 days apart, followed by every-two-week injections up to week 22. All then will be followed for another 14 weeks.

Among the initial eight patients, six received treatment for 12 weeks and were followed for a similar amount of time, while two patients remained on treatment for the whole 24 weeks.

NfL levels

Preliminary data showed that ANX005 treatment resulted in a reduction in neurofilament light chain (NfL) levels, a marker of nerve cell damage, during the initial 12 weeks of treatment. But levels rose to their initial value when patients stopped receiving treatment.

In the first 12 weeks, all patients also showed a slowing or halting of disease progression, as determined by changes in the Revised ALS Functional Rating Scale. But, while the six patients who who went off treatment after the initial 12 weeks experienced functional declines in the following 12 weeks, those who remained on treatment continued to improve.

Because the study is open-label, both researchers and patients are aware of the treatment being given.

“We envision a world in which every person gets to live out their talents, without being robbed of their physical and cognitive health due to disease. Our mission is to free the body, brain and eye from diseases driven by the classical complement cascade,” Douglas Love, president and CEO of Annexon, said in the release.

“To achieve this, we’ve purposefully developed a broad pipeline across three therapeutic franchises — autoimmune, neurodegeneration and ophthalmology — allowing us to rigorously evaluate an array of diseases for which the classical pathway drives disease burden,” he added.