Supplementary analyses to topline Phase II results reveal additional RP101 clinical strengths

• RP101 demonstrates treatment difference versus control (Intelligel vehicle) in inferior corneal staining with robust and significant improvement
• SANDE symptom score also reveals significant treatment difference versus control in a subgroup of more severe patients
• Both inferior corneal staining and SANDE endpoints have been accepted by the US FDA for clinical endpoints in other dry eye programs
• RP101 is well-positioned for continued development in a larger pivotal clinical trial

(December 29, 2020, Stockholm, Sweden) - After publishing topline Phase II results of the RP101 Phase II clinical trial on March 12, 2020, Redwood Pharma engaged Ora®, Inc., a leading global ophthalmic research organization to complete an independent in-depth analysis. This follow-on analysis complementing the original trial protocol reveals further key evidence of the candidate’s therapeutic strengths.

“The topline analysis of RP101 showed significant improvement over the course of the 90-day trial of pre-defined primary and secondary endpoints. These improvements were statistically significant from the levels (baseline) in which the patients showed at the start of the trial. Although the initial analysis did not reveal any difference in treatment over control (vehicle) of these pre-defined endpoints, the new analyses reveal the opposite when other endpoints and subgroups in the same patient population are studied. The fact that the RP101 Phase II trial also reveals robust and significant treatment difference over control on endpoints means that the program has markedly improved its chances of clinical success and commercialization. We are deeply encouraged by these compelling results as they reinforce the body of very positive clinical evidence in objective signs and subjective symptoms of the Phase II trial,” states CEO Martin Vidaeus.

Objective and subjective endpoints in dry eye clinical research

A mix of endpoints are used in the design of dry eye clinical trials to, among other reasons, help clinicians and regulators objectively quantify dry eye disease improvement – and to confirm through patients’ subjective reporting that medicines are actually making them feel better.

From a developer of pharmaceuticals and regulatory authority’s (i.e. the US FDA) perspectives, the goals of a Phase II clinical trial are to evaluate safety and efficacy, and also to determine the basis for further development including optimal dosing and primary and secondary endpoints.

To obtain market approval after Phase III trials, results need to show treatment significance over vehicle (placebo) in one objective (measurable) endpoint in dry eye disease management such as tear fluid production, tear film break up time or fluorescein corneal staining (i.e. total corneal staining) and also for one subjective endpoint. Patient-reported subjective measures such as the SANDE questionnaire, pain and foreign body sensation allow for quantification how a patient feels.  

Initial RP101 Phase II results

RP101 demonstrated significant efficacy over patients’ starting (baseline) values in multiple objective and subjective endpoints. The primary objective endpoint, tear fluid production measured by the Schirmer test, demonstrated a desirable quick onset of effect already at 14 days, and maintained improvement through the end of the study at Day 90. Tear fluid increased over 150% with RP101 (0.1% concentration administered twice daily). Total corneal staining show quick onset from baseline at 14 dyas, but no difference from vehicle. Likewise, the subjective SANDE score endpointrevealed significance over baseline as early as Day 30 and through Day 90. This symptom assessment, along with 11 other subjective secondary endpoints, demonstrated significant improvement over baseline at Day 90.

There were no statistical differences between groups, nor any significant treatment difference between the three RP101 groups and vehicle (Intelligel) according to the protocol of analyses Redwood Pharma had initially set out to perform.

New findings

Redwood Pharma engaged leading dry eye experts at Ora, Inc., Andover, MA, USA to further review the Phase II data with a view to determining next steps in clinical development. During this analysis, new findings showed that RP101 demonstrated statistically significant treatment effect on corneal damage assessed by corneal staining, and more specifically on the inferior part of the cornea (one of five zones on the cornea that in aggregate comprise the total corneal staining endpoint). RP101 (0.1% concentration administered twice daily) showed an improvement from baseline of 1.1 units, but more importantly, a 0.70 unit significant (P=0.0463) treatment difference over vehicle (control) at 90 days. These results are encouraging when considering that Xiidra®[1], which obtained FDA approval in large part on inferior corneal staining, demonstrated an improvement of less than 0.1 unit (p=0.0007) (Xiidra OPUS-1 value at Day 84) after 3 months of dosing in a Phase III study including more than 5 times the number of subjects[2]. It should, however, be noted that the patient populations in the studies were not identical.

Ora’s analysis of the RP101 Phase II data also revealed that the SANDE score, in a subgroup of more severe patients, showed significant improvement over the vehicle-control group in RP101 (0.1% concentration administered twice daily).The Day 90 total SANDE score (change from baseline) was reduced by -22.5 on the visual analog scale (VAS) in favor of RP101 (p = 0.0185). Significant signals were also shown for SANDE frequency (p=0.0022) and severity (p=0.0067) at Day 90.

“These new positive results confirm the clinical strength of the RP101 program and strengthen the foundation for successful further development. The findings of treatment significance over vehicle facilitate the design of a new, larger, potentially pivotal trial. We look forward to sharing these results in our partnering discussions,” states CEO Martin Vidaeus.

[1] Trademark by Novartis

[2] https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208073s000lbl.pdf

For more information:

Martin Vidaeus, CEO Redwood Pharma AB (publ)
Tel: +46 (0) 70 232 29 29
E-mail: martin.vidaeus@redwoodpharma.com

This information is information that Redwood Pharma AB is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact persons set out above, December 29, 2020.

About Redwood Pharma
Redwood Pharma develops ophthalmic products for unmet medical needs through novel approaches. In providing commercial partners and their customers with effective medical solutions, the Company is currently developing treatments for dry eye disease in various target patient populations. The RP101 program targets moderate-to-severe dry eye disease in postmenopausal women by delivering a low-dose estrogen therapy to the front of the eye. The RP501 program aims to treat milder forms of dry eye in a broader patient population including both men and women of all ages. For other potential drug substances and therapeutic areas, the Company can employ the IntelliGel drug delivery platform that enhances patient convenience by controlling dosing and potentially reducing the number of instillations per day and subsequent side-effects. Redwood Pharma leverages its strengths in early clinical development and aims to generate revenues through, among others, licensing agreements with companies that have capabilities to manufacture and sell medical products worldwide.

Redwood Pharma AB (publ) is listed on the Spotlight Stock Market (Ticker: REDW.ST, ISIN: SE008294789).

About Ora^®, Inc.
Ora is the world’s leading full-service ophthalmic research organization with offices in the United States, United Kingdom, Australia, and Asia. For over 40 years, Ora has helped clients earn more than 45 product approvals. For more information, please visit www.oraclinical.com.