Dosing Cohort 2 Completed in Phase I Hutrukin Study

August 21, 2023

Cohort 2 of XBiotech’s Phase I study for Hutrukin have now completed dosing and safety evaluation. Hutrukin was well tolerated and the study will now begin enrolling subjects into Cohort 3.

Hutrukin is a novel candidate treatment for reducing brain injury after stroke. If a blood clot occurs in an artery supplying blood to the brain, the blocked artery results in loss of blood supply which starves the brain of oxygen (ischemia). The loss of oxygen to the brain as a result of a blot clot is known as an ischemic stroke. Clot-busting drugs and or devices such as catheters have been developed to re-open clogged arteries after a stroke. Surprisingly, however, opening a clogged artery may not reduce the harm from the stroke. In fact, after opening the clot, the return of blood supply to ischemic brain (reperfusion) can result in aggravation of ischemic injury, with a rapid expansion of brain damage.

Hutrukin is being developed as a drug that is given immediately prior to clot-busting procedures, where it is intended to reduce injury associated with reperfusion. There is currently no drug available to treat reperfusion injury. Hutrukin, has the potential to be a novel, breakthrough therapy in the management of ischemic stroke, the second most common cause of death or disability worldwide.

XBiotech is conducting a Phase I study to evaluate safety and pharmacokinetics of Hutrukin in healthy volunteers. The study involves sequential dose escalation, using three groups (or cohorts) of subjects, receiving a single intravenous infusion of either placebo or Hutrukin at 1,000 mg (Cohort 1), 3,000 mg (Cohort 2), or 5,000 mg (Cohort 3) dose levels, respectively. Dose escalation will utilize a 6+2 design with sentinel dosing and doses will be explored with 8 subjects in each cohort (6 subjects are dosed with Hutrukin and 2 subjects with placebo).

Dosing Cohort 1 Completed with no Safety Concerns in Phase I Hutrukin Healthy Volunteer Study

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May 17, 2023

XBiotech is conducting a Phase I study to evaluate safety and pharmacokinetics of its candidate stroke therapy Hutrukin in healthy volunteers. The study uses sequential dose escalation involving three groups (or cohorts) of subjects to prove Hutrukin tolerability. Participants receive a single intravenous infusion of either placebo or active drug Hutrukin at either 1,000 mg (Cohort 1), 3,000 mg (Cohort 2), or 5,000 mg (Cohort 3) dose levels. Dose escalation will utilize a 6+2 design with sentinel dosing and doses will be explored with 8 subjects in each cohort (6 subjects are dosed with Hutrukin and 2 subjects with placebo).

Subjects in Cohort 1 have now completed dosing and safety evaluation. Hutrukin was well tolerated in all subjects. The study will now begin enrolling subjects into Cohort 2.

Hutrukin is a novel treatment to reduce brain injury as part of urgent therapy for stroke victims. If a blood clot occurs in an artery that supplies blood to the brain, the loss of blood supply starves a portion of the brain of oxygen (ischemia). This is known as an ischemic stroke. Clot-busting drugs and/or catheters can be used to re-open the clog artery. However, surprisingly, after opening of the clogged artery, return of blood supply to ischemic brain can result in aggravation of ischemic injury, often with a rapid expansion of brain damage.

Hutrukin is intended to be given immediately prior to clot-busting procedures. Hutrukin is intended to reduce reperfusion injury associated with the resumption of blood supply to the hypoxic brain tissue. There is currently no drug available to treat reperfusion injury. Hutrukin, therefore, has the potential to be a novel, breakthrough therapy in the management of ischemic stroke. Stroke is the second most common cause of death or disability worldwide.

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New Non-Clinical Toxicology and Ex-vivo Clinical Pharmacodynamic Studies Support Safety and Guide Optimal Dosing Frequency in Rheumatoid Arthritis (RA) Patients

April 26, 2023

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-1 (IL-1), a substance naturally produced by the body in response to injury. IL-1 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-1 activity may cause undesired inflammation, destruction of healthy tissue, pain and malaise. In arthritis, IL-1 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-1 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-1, and does not effectively block the activity of IL-1 in animals. A so called “surrogate antibody” to block IL-1 in animals was therefore needed. XBiotech used a mouse derived antibody that blocks mouse related IL-1.

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.