Clearside Biomedical lost more than half its stock value today after it said it was scrapping clinical development of its lead candidate Xipere (formerly suprachoroidal CLS-TA) for retinal vein occlusion (RVO) after it failed a Phase III combination trial.
Xipere failed the Phase III SAPPHIRE trial (NCT02980874), designed to assess the combination of Xipere with the Regeneron/Bayer co-marketed eye treatment Eylea® (aflibercept), a vascular endothelial growth factor (VEGF) inhibitor.
SAPPHIRE’s primary endpoint was the proportion of patients in the combination treatment arm, compared to the intravitreal Eylea-alone control arm, with improvements in best corrected visual acuity (BCVA) from baseline of at least 15 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale at eight weeks after initial treatment.
While approximately 50% of patients in both arms showed at least a 15-letter improvement in vision, there was no additional benefit for patients receiving Xipere together with intravitreal Eylea, Clearside Bio acknowledged.
“In light of these eight-week topline data, we plan to discontinue clinical development of combination therapy for RVO,” Clearside CEO and president Daniel White said in a statement.
As a result, he said, Clearside will also end the companion Phase III TOPAZ trial, (NCT03203447), which is designed to assess the safety and efficacy of Xipere and one of two Genentech, a member of the Roche Group, intravitreal anti-VEGF agents, Lucentis® (ranibizumab) or Avastin® (bevacizumab) in treatment naïve patients with RVO.
News of the clinical setback sent Clearside sparked a stock sell-off that sent shares plunging this morning on NASDAQ by nearly 58% from Friday’s closing price of $5.56, to $2.35 as of 10:04 a.m.
White added that Clearside would continue developing Xipere in its primary indication of uveitis, describing as “very attractive” the development opportunity in that indication: “Awareness and acceptance of the strong clinical profile of Xipere as a potential monotherapy in treating uveitic macular edema is growing, and we remain on track to submit our NDA for this indication before the end of this year.”
Xipere is also in development for diabetic macular edema (DME), where the candidate is under study in the Phase II TYBEE trial (NCT03126786), designed to evaluate the safety and efficacy Xipere with intravitreal Eylea.
SAPPHIRE was a multicenter, multicountry, randomized, masked, controlled Phase III trial that enrolled 460 patients with treatment naïve RVO. The safety profile appeared consistent with previous studies of XIPERE through eight weeks.