Sling Therapeutics announced topline efficacy and safety data from the Phase 2b/3 LIDS trial of linsitinib in patients with active, moderate to severe thyroid eye disease (TED). The LIDS trial met its primary endpoint with statistical significance for the 150 mg BID dose, the company said in a press release. Linsitinib in this trial validated the safety profile seen in the prior oncology studies and demonstrated a favorable safety profile on key adverse events (AEs) of interest for the IGF-1R target such as hearing impairment, hyperglycemia, and menstrual cycle changes. Additionally, no QTc prolongation was observed in any patient with rigorous ECG monitoring throughout the study, the company said.

Key findings from the study showed that Proptosis Responder Rate (PRR) was statistically significant and clinically meaningful at the 150 mg BID dose, with a PRR of 52% (p = 0.01) at Week 24. In addition, Linsitinib was well-tolerated and consistent with the safety profile of the previous 15 linsitinib clinical trials, which now includes more than 900 patients in multiple disease areas. 

Key AE data from the 150 mg BID arm include:

• No drug-related hearing impairment reported (1 unrelated report out of 29 patients)
• 0% tinnitus placebo-adjusted rate
• 3% rate of hyperglycemia (1 report out of 29 patients with no intervention required)
• 0% menstrual cycle changes reported
• Treatment emergent AEs greater than or equal to 10%: diarrhea (20.7%), headache (20.7%), nausea (20.7%), fatigue (17.2%), ALT increase (17.2%), hyperhidrosis (13.8%), AST increase (10.3%), and muscle spasms (10.3%)
• Hepatic transaminases were all quickly resolved and not associated with any elevations of total bilirubin, alkaline phosphatase, hepatic dysfunction, or other signs or symptoms of drug-induced liver injury
• The majority of AEs were either mild or moderate, reversible, and quickly resolved upon treatment pause or discontinuation consistent with a shorter half-life treatment
• No QTc prolongation was observed in any patient with rigorous monitoring throughout the study

The company said it is engaging with regulatory authorities to discuss the confirmatory Phase 3 trial design, which is on track to commence in 2025. Full results of this Phase 2b/3 trial will be presented at an upcoming medical conference.

The LIDS Phase 2b/3, randomized, double-masked, placebo-controlled study was designed to evaluate the safety, pharmacokinetics, and efficacy of the company’s lead product candidate, linsitinib (an oral small molecule that is taken twice-daily), in patients with active, moderate to severe TED. The primary endpoint of the study was the percentage of subjects who were proptosis responders at week 24, defined as at least a two-millimeter reduction in proptosis from baseline. The LIDS trial enrolled 90 patients who were randomized 1:1:1 and received either linsitinib 150 mg BID, linsitinib 75mg BID, or placebo for 24 weeks. The trial was conducted globally at 35 sites in five countries.