Shares in Georgia small-cap Clearside Biomedical are in free fall this morning after the biotech revealed its top pipeline drug failed a phase 3 trial in retinal vein occlusion, a common cause of vision loss.
Clearside was down more than 50% in premarket trading on the news that Xipere—previously known as suprachoroidal CLS-TA (triamcinolone acetonide)—added zero benefit when given with Regeneron’s anti-VEGF drug Eylea (aflibercept), a standard therapy for macular edema caused by RVO.
Clearside’s CEO Daniel White summed the trial up as follows: “In the SAPPHIRE trial, approximately 50% of patients in both arms showed at least a 15-letter improvement in vision; unfortunately, there was no additional benefit for patients receiving Xipere together with intravitreal Eylea.”
Meanwhile, Clearside Chief Scientific Officer Glenn Noronha, Ph.D., said on a conference call that it was possible that Eylea therapy was working so well it created a ceiling effect, which made it hard for Xipere to show any upside.
The Alpharetta-based company, which went public in 2016, is abandoning Xipere for RVO and will halt a second phase 3 trial called TOPAZ in the same patient population, putting even more emphasis on getting approval for the drug in macular edema associated with non-infectious uveitis, its lead indication. There are no currently approved treatments for uveitic macular edema.
According to White, Clearside is still planning to file for approval of Xipere as a monotherapy in uveitis before year-end based on the results of the phase 3 PEACHTREE trial. It’s cold comfort, but stopping SAPHIRE and TOPAZ at least leaves the company with the cash it needs to operate into 2020.
The company also has a diabetic macular edema (DME) program in phase 2, which, as with RVO, is looking at the drug as an add-on to Eylea therapy and in light of the latest data is currently under review.
The SAPHIRE fail isn’t completely unexpected, as an earlier phase 2 trial achieved only borderline statistical significance for the corticosteroid formulation, which is injected into the suprachoroidal space of the eye. It’s a delivery route that—at least in theory—should have fewer side effects than treatment injected directly into the vitreous body and require fewer treatments and doctor visits.
While the phase 2 trial met its primary and secondary endpoints investors were scared by the data, which suggested Xipere was actually performing less well than Eylea, prompting another share selloff.
“We believe the opportunity in our primary indication, uveitis, remains very attractive,” said White, who told analysts on the call that a uveitis monotherapy indication would be enough to sustain the company on its own while it explores additional indications for Xipere and its novel delivery route.
“Awareness and acceptance of the strong clinical profile of Xipere as a potential monotherapy in treating uveitic macular edema is growing,” he added.