SON-080 May Decrease Chemotherapy-Induced Peripheral Neuropathy

In the phase 1b portion of this trial (NCT05435742), patients were given SON-080 at 20 µg and 60 µg; the agent was well-tolerated at both levels.

SON-080 yielded encouraging topline data from the phase 1b portion of the SB211 trial (NCT05435742) assessing persistent chemotherapy-induced peripheral neuropathy (CIPN) in patients who have received prior chemotherapy, according to a press release from Sonnet BioTherapeutics.¹

In the trial, patients were given SON-080 at 20 µg and 60 µg; the agent was well-tolerated at both levels. It was noted this was 10-fold lower than the maximum-tolerated dose for interleukin-6 (IL-6) based on prior studies. The most common treatment-related adverse effect (AE) was injection site erythema. All cases except for 1 at each dose level were transient to mild, with the outlier being moderate.

With the higher dose of SON-080, fatigue was more prominently reported. Severe fatigue developed in 1 patient in the 20 µg group who stopped dosing after 1 month. In the 60 µg group, headaches, dizziness, and chills were all reported at infrequent levels.

A primary indicator of response was the quality-of-life questionnaire-CIPN twenty-item scale, which assessed patients with cancer symptoms and functional limitations related to CIPN. Investigators noted that a trend towards an improved score was found 1 month after beginning therapy and observed in both groups vs placebo. This improvement continued for 12 weeks after therapy was stopped, and the placebo group had scores that returned to baseline.

The safety evaluation studied multiple cytokines, but there was no demonstratable drug effect on any cytokine serum levels during or after therapy with SON-080. An increase in serum amyloid alpha persisted throughout therapy but returned to baseline after it stopped.

SON-080 is a low-dose recombinant human IL-6 treatment. The trial will assess this treatment, which has an amino acid sequence identical to the native molecule. Additionally, this agent will target serum levels similar to those of when moderate exercise ensues, potentially yielding natural healing of nerves, muscle, and bone.

"These data suggest possible benefits in humans with various types of peripheral neuropathy due to cancer and diabetes. [IL-6] has been extensively studied in patients with cancer in the past, so the use of SON-080 in CIPN was expected to provide a similar [AE] profile at low doses," Richard Kenney, MD, Sonnet’s chief medical officer, said in the press release.¹ "We now have a further understanding of the [AE] profile and the opportunity to look at preliminary efficacy trends. We look forward to initiating a phase 2 study with a partner in the much larger [diabetes peripheral neuropathy] indication."

In March 2024, a data and safety monitoring board reviewed and unblinded the results from the first 9 patients.² They concluded that symptoms were tolerable, and phase 2 could commence.

The SB211 trial assessed patients with CIPN that was persistent for at least 3 months after chemotherapy.³ Patients received treatment for 12 weeks with a 12-week follow-up period.

The primary end point was to evaluate the safety of SON-080. Secondary end points were to evaluate the pharmacokinetics, immunogenicity, and preliminary efficacy.

Patients were included in the trial if they had a history of cancer that was stable or in remission, received treatment with a chemotherapeutic agent, and had an ECOG score of 0 or 1. Additionally, a patient or caregiver must have been able to administer subcutaneous treatment at home.

Patients were excluded if investigators found another cause of chemotherapeutic neuropathy, unresolved toxicities from prior anticancer therapy, an active COVID-19 infection, or a history of hepatic disease.

The developers are also investigating how SON-080 will impact diabetic peripheral neuropathy and will continue trials in both spaces.

References

1. Sonnet BioTherapeutics reports encouraging data from phase 1b/2a clinical trial of SON-080 in chemotherapy-induced peripheral neuropathy (CIPN) that support advancement into phase 2 study. News release. Sonnet BioTherpautics. July 24, 2024. Accessed July 25, 2024. https://shorturl.at/Jx81z
2. Sonnet BioTherapeutics announces early safety data from the company’s phase 1b/2a clinical trial of SON-080 in chemotherapy-induced peripheral neuropathy (CIPN) met the study’s initial pre-specified objective. News release. Sonnet BioTherpautics. March 11, 2024. Accessed July 25, 2024. https://shorturl.at/PA9QZ
3. SON-080 in patients with persistent chemotherapy-induced peripheral neuropathy (CIPN). ClinicalTrials.gov. Updated April 12, 2024. Accessed July 25, 2024. https://shorturl.at/k6qcM