“We remain on track to submit our first NDA before the end of this year and are continuing to make significant progress in advancing our late-stage pipeline,” said
Update on Key Development Programs
Suprachoroidal CLS-TA, Clearside’s first investigational treatment program, is a proprietary suspension of the corticosteroid triamcinolone acetonide formulated for administration to the back of the eye via the suprachoroidal space, or SCS®, which is the space located between the choroid and the outer protective layer of the eye known as the sclera. Clearside’s proprietary suprachoroidal treatment approach is designed to enable rapid dispersion of a high amount of medicine to the back of the eye so that adequate medicine reaches and stays at the site of disease and has potential to act longer. This approach has potential to provide efficacy advantages and require fewer treatments and office visits while minimizing harm to the surrounding healthy parts of the eye.
Macular Edema Associated with Non-Infectious Uveitis
Clearside expects to submit a New Drug Application (“NDA”) for suprachoroidal CLS-TA to treat macular edema associated with non-infectious uveitis to the
In this first public presentation of data from the PEACHTREE trial at a medical conference, Dr. Yeh highlighted that, as previously reported, this 24-week study met its primary endpoint, with 47% of patients in the treatment arm who received suprachoroidal CLS-TA every 12 weeks gaining at least 15 letters in best corrected visual acuity (“BCVA”), as measured using the Early Treatment of Diabetic Retinopathy Study (“ETDRS”) scale, from baseline at week 24, compared to 16% of patients in the control arm who underwent a sham procedure (p<0.001). The mean change in BCVA from baseline was better in the treatment arm than in the sham control arm at each monthly evaluation. The mean improvement from baseline seen at the first evaluation at week 4 was maintained throughout the trial, with 9.6 letters gained at week 4 and 13.8 letters at week 24 in the treatment arm, compared to 1.3 letters at week 4 and 3.0 letters at week 24 in the sham control arm. In addition, administration of suprachoroidal CLS-TA resulted in a mean reduction from baseline of 153 microns in central subfield thickness (“CST”) of the retina at week 24 in the treatment arm, compared to an 18 micron mean reduction in the sham control arm, a result that was also statistically significant (p<0.001). Suprachoroidal CLS-TA was generally well tolerated, with no treatment-related serious adverse events reported in the trial.
Dr. Yeh also presented additional highlights from the PEACHTREE trial, which are summarized below:
- 52% of patients in the treatment arm could read 70 or more ETDRS letters, the minimum legal limit to qualify for a driver’s license in most states, at week 24, compared to 22% of patients in the control arm;
- Over 85% of the patients in the treatment arm did not require rescue therapy, compared to 28% of patients in the control arm; and
- With respect to safety, based on an analysis which included patients who received rescue therapy, elevated intraocular pressure ("IOP") adverse events pertaining to corticosteroid use were reported for 11.5% (11/96) of patients in the treatment arm, compared to 26.3% (10/38) of patients rescued with local corticosteroids, such as intravitreal OZURDEX® (dexamethasone intravitreal implant) and subtenon and intravitreal triamcinolone acetonide in the sham control arm, resulting in an overall rate of 15.6% (10/64) of patients in the sham control arm through 24 weeks.
“We were honored to share the PEACHTREE data with researchers and clinicians at such an important forum as ASRS,” said Mr. White. “Our confidence in the potential of suprachoroidal CLS-TA, if approved, to become a new treatment option for non-infectious uveitis continues to grow, and we are beginning to build our commercial infrastructure to support that.”
Macular Edema Associated with Retinal Vein Occlusion (“RVO”)
While suprachoroidal CLS-TA is being studied as a monotherapy in macular edema associated with non-infectious uveitis, Clearside is studying suprachoroidal CLS-TA together with an intravitreal anti-vascular endothelial growth factor (“anti-VEGF”) agent in other retinal vascular diseases, such as RVO and diabetic macular edema, which have a high vascular endothelial growth factor response to disease.
RVO is a particularly aggressive eye disease resulting from an occlusion in a vein carrying blood out of the retina. This blockage can lead to the rapid onset of complications, including sudden declines in vision.
The objective of the SAPPHIRE trial is to show that suprachoroidal CLS-TA used together with an intravitreal anti-VEGF agent may result in earlier, superior visual acuity outcome as compared to monthly injections of an intravitreal anti-VEGF alone in newly diagnosed branch retinal vein occlusion (“BRVO”) and central retinal vein occlusion (“CRVO”) patients.
“Ideally, we would like to see better visual outcomes in the early phase of the disease like we saw in our Phase 2 Tanzanite study, where 52% of patients receiving combination treatment recovered 3 lines of vision by month 1, compared to 39% of patients receiving Eylea alone,” said Mr. White. “If we achieve similar results in SAPPHIRE, we believe that this Phase 3 study has the potential to demonstrate a better opportunity to recover vision earlier and potentially preserve those vision gains over the long term. We look forward to reporting topline 8-week primary endpoint data from the Phase 3 SAPPHIRE trial in the fourth quarter of 2018.”
Clearside also continues to enroll patients in SAPPHIRE’s companion Phase 3 trial, TOPAZ, of suprachoroidal CLS-TA with one of two intravitreal anti-VEGF agents, LUCENTIS® (ranibizumab) or AVASTIN® (bevacizumab), in treatment naïve patients with RVO.
If the primary endpoints are met in both the SAPPHIRE and TOPAZ trials, Clearside intends to seek a class label in
Diabetic Macular Edema (“DME”)
Patients in both the combination arm receiving suprachoroidal CLS-TA together with intravitreal Eylea and the control arm receiving Eylea alone achieved a statistically significant improvement in mean BCVA at week 24 from baseline (p<0.001). The combination arm achieved a statistically similar outcome to Eylea alone at every visit, including at week 24, with fewer treatments.
Additionally, patients showed [statistically] significantly better resolution of CST in the combination arm at week 4 compared to the resolution in the Eylea alone arm (p<0.01); the greater resolution seen in the combination arm was sustained through the end of the study.
Suprachoroidal CLS-TA used together with intravitreal Eylea was generally well tolerated, with no treatment-related serious adverse events reported through the 24-week evaluation period. Elevated IOP adverse events were reported for 8.3% (3/36) of patients in the combination arm, compared to 2.9% (1/35) of patients in the control arm. Cataract adverse events were reported for 5.6% (2/36) of patients in the combination arm and 2.9% (1/35) of patients in the control arm.
“We are pleased with the topline results of the Phase 2 TYBEE trial, which signals the potential utility of suprachoroidal CLS-TA to improve on the existing standard of care in DME,” stated Mr. White. “Like in our RVO program, we observed positive outcomes in vision, meaningful improvements in CST and fewer incidences of elevated IOP events than typically associated with local administration of corticosteroids. As we receive the complete data set, we will work closely with our scientific and medical advisors to evaluate the outcomes of the TYBEE trial and develop a plan forward for this program.”
Pipeline and Collaborations
Clearside continues nonclinical efforts, both internally and with multiple collaborators, in other ocular diseases and technologies that may benefit from a suprachoroidal treatment approach.
Second Quarter 2018 Financial Results
Clearside’s research and development expenses for the three months ended
General and administrative expenses were
Net loss for the second quarter of 2018 was
Cautionary Note Regarding Forward-Looking Statements
Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “believe”, “expect”, “may”, “plan”, “potential”, “will”, and similar expressions, and are based on Clearside’s current beliefs and expectations. These forward-looking statements include expectations regarding the potential clinical development of Clearside’s product candidates, the availability of data from Clearside’s clinical trials, the timing of a potential submission of an NDA with the
CLEARSIDE BIOMEDICAL, INC.
Selected Financial Data
(in thousands, except share and per share data)
|Statements of Operations Data||Three Months Ended
|Six Months Ended
|License and collaboration revenue||$||—||$||130||$||—||$||135|
|Research and development||17,343||11,478||30,722||19,068|
|General and administrative||3,561||2,290||6,635||4,961|
|Total operating expenses||20,904||13,768||37,357||24,029|
|Loss from operations||(20,904||)||(13,638||)||(37,357||)||(23,894||)|
|Other income (expense), net||203||(135||)||49||(252||)|
|Net loss per share of common stock — basic and diluted||$||(0.65||)||$||(0.54||)||$||(1.27||)||$||(0.96||)|
|Weighted average shares outstanding — basic and diluted||31,979,158||25,309,966||29,412,904||25,280,314|
|Balance Sheet Data||June 30,||December 31,|
|Cash, cash equivalents and short-term investments||$||84,430||$||37,640|
|Long-term debt (including current portion)||9,848||8,009|
|Total stockholders’ equity||66,672||21,415|
As Clearside prepares to transition from a clinical-stage to a commercial-stage company, Mr. Rodríguez will be responsible for ensuring that the company continues to design and implement appropriate programs, policies and procedures related to quality assurance and quality control activities across the company and its suppliers. He will also provide cross-functional compliance oversight of activities involving all recognized quality standards for the pharmaceutical industry, such as good manufacturing practices and good clinical practices.
Mr. Rodríguez is an accomplished quality management professional with over 30 years of experience in the pharmaceuticals industry. Before joining Clearside, Mr. Rodríguez was Vice President of Quality for
“Lester is a seasoned quality leader who brings to Clearside a wealth of experience and expertise in pharmaceutical quality assurance, quality control, and quality systems management,” said Clearside’s Chief Executive Officer and President,
Cautionary Note Regarding Forward-Looking Statements
Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “believe”, “expect”, “may”, “plan”, “potential”, “will”, and similar expressions, and are based on Clearside’s current beliefs and expectations. These forward-looking statements include expectations regarding the clinical development of Clearside’s product candidates, the timing of a potential submission of an NDA with the