XBiotech Submits New Non-clinical Safety and Pharmacodynamic Data to the FDA in Support of Natrunix Therapy

XBiotech submitted a complete safety and pharmacokinetic-pharmacodynamic package to the FDA in support of its proposed Phase II Clinical Study of Natrunix in rheumatoid arthritis patients.

Natrunix works to block the activity of interleukin-1a (IL-1a), a substance naturally produced by the body in response to injury. IL-1a stimulates inflammation, heightens sensitivity to pain, breakdowns connective tissue scaffolding that provides support to body tissues, induces new blood vessel formation and acts as a messenger notifying the brain of injury. Under disease conditions, IL-1a activity may cause undesired inflammation, destruction of healthy tissue, pain and malaise. In arthritis, IL-1a may play a crucial role in joint inflammation, destruction of synovial tissue and joint pain.

Natrunix was derived from—and is indistinguishable from—a naturally occurring antibody present in a healthy human. The use of Natrunix in arthritis is expected to be extremely safe, and XBiotech believes that the drug represents a breakthrough treatment for the disease, which affects 54 million people in the US, and is the leading cause of disability (American Arthritis Foundation).

After discovery, testing and development of Natrunix, XBiotech planned to compare Natrunix head-to-head in clinical trials to methotrexate—which is the current treatment standard for arthritis. Methotrexate is a cytotoxic and immunosuppressive drug with well-known and extensive list of serious toxicities and side effects. XBiotech has blocked IL-1a in multiple prior human clinical trials with no known toxicity. However, in response to XBiotech’s investigational new drug application, in 2022 the FDA recommended that additional studies be performed in animals to further examine the safety of Natrunix before human clinical trials could begin.

Since Natrunix is a human antibody, it is highly specific to human IL-1a, and does not effectively block the activity of IL-1a in animals. A so called “surrogate antibody” to block IL-1a in animals was therefore needed. XBiotech used a mouse derived antibody that blocks mouse related IL-1a.

In the recently completed study, mice were given twelve weekly doses of the surrogate antibody—at up to 50-fold excess over the intended human clinical dose—and monitored for toxicity. The study evaluated a standard battery of safety endpoints including clinical signs, clinical pathology (hematology, and clinical chemistry), macroscopic and microscopic evaluation of an exhaustive list of tissues, ophthalmologic and toxicokinetic analysis. No study drug related changes of any kind were observed in any animal.

The FDA also requested additional dose justification and mechanism of action data for Natrunix to support its use in treating arthritis. XBiotech developed these data using an innovative ex vivo pharmacodynamic model generated by researchers at XBiotech (see news release ‘XBiotech Shows How Natrunix Stops Inflammation in Synovial Cells Taken from Rheumatoid Arthritis Patients’ published online on 14 March 2023). These data confirmed the ability of Natrunix to stop production of inflammation causing substances and tissue degrading enzymes from synoviocytes isolated from joints of arthritis patients.

All these findings have now been provided to the FDA as part of an extensive package of requested additional information. The human study for Natrunix in arthritis is on clinical hold until the FDA reviews the current data and determines whether they believe Natrunix is safe enough to begin clinical studies. The timing for feedback or approval from the FDA is unknown at the present time.