Mereo BioPharma Group PLC (MREO)

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NEWS
Mereo BioPharma Provides Regulatory Updates on Alvelestat for the Treatment of Alpha-1-Antitrypsin Deficiency-Associated Lung Disease
Clear path forward with proposed single Phase 3 study evaluating alvelestat at the 240 mg dose level versus placebo at 12-18 months for potential full approval in both the U.S. and EU

No additional confirmatory study required

Company to host conference call today at 8:30am ET

LONDON, March 21, 2023 (GLOBE NEWSWIRE) -- Mereo BioPharma Group plc (NASDAQ: MREO) (Mereo or the Company), a clinical-stage biopharmaceutical company focused on rare diseases, today announced regulatory feedback following recent end-of-Phase 2 meetings with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) related to its alvelestat program for the treatment of alpha-1-antitrypsin deficiency-associated lung disease (AATD-LD).

Based on clear recommendations from the FDA and the EMA, the Company is designing a single, global, Phase 3 study evaluating the 240 mg dose of alvelestat versus placebo in patients with AATD-LD to support applications for full marketing approvals in both the United States (U.S.) and European Union (EU). The Company’s proposed Phase 3 study has two independent primary endpoints, i) a Patient-Reported Outcome (PRO), as guided by the FDA, and ii) lung density measured by CT scan, as guided by the EMA.

In line with previous guidance by the Company, Mereo is exploring potential partnerships to fund the Phase 3 study, and believes that this clear path forward will support these efforts.

Each of the proposed primary endpoints has been shown to be associated with reductions in certain disease activity biomarkers. The proposed PRO of the St. George’s Respiratory Questionnaire (SGRQ) Activity domain was shown to be associated with the reduction of desmosine and Aa-Val360 in the Company’s Phase 2 ASTRAEUS study. The association of desmosine reduction with lung density measured by CT scan was demonstrated in published clinical data in AATD 1.

Both the FDA and EMA recognize the challenges associated with development of new therapeutics for AATD-LD. Consistent with an openness to supporting the advancement of therapeutic development in this space, the EMA has indicated that for the primary endpoint of lung density measured by CT scan, it would accept a more relaxed Type 1 error (i.e., p<0.1) for a potential full approval that is not contingent on the outcome of a confirmatory study. Additional supportive secondary endpoints are being proposed, including biomarker-based endpoints that may provide sufficient data to validate the biomarkers for future studies.

If successful, this proposed Phase 3 study, with an expected duration of 12-18 months and an enrollment target of approximately 200 patients, is expected to support full regulatory approvals in both the U.S. and EU without an additional confirmatory trial. This could provide the Company with a path to full approval of alvelestat based on a Phase 3 trial similar in size and length to what would be required for an accelerated or conditional approval based on biomarkers. Mereo also believes that this proposed study, if successful, will support more productive initial reimbursement discussions with payors following potential regulatory approvals.

“We are very pleased with the feedback from our meetings with both the FDA and EMA, and grateful for the thorough guidance each Agency provided and the clear path forward that the Agencies have each outlined for alvelestat,” said Dr. Denise Scots-Knight, Chief Executive Officer of Mereo. “We believe this is the first time a proposed registrational study in AATD-LD will use both a Patient-Reported Outcome approach, and an objective clinical outcome measure of lung density measured by CT scan as independent primary endpoints, allowing for a clinical trial with a reasonable number of patients conducted over a manageable timeframe. We believe this represents a significant step forward in the development of new therapies for AATD-LD, and we look forward to further collaboration with both Agencies as we refine the Phase 3 study design to support alvelestat’s continued efficient clinical development and its timely availability for patients.”

1: Ma et al. The Effect of Alpha-1 Proteinase Inhibitor on Biomarkers of Elastin Degradation in Alpha-1 Antitrypsin Deficiency: An Analysis of the RAPID/RAPID Extension Trials. Chronic Obstr Pulm Dis. 2017;4(1):34-44

Conference Call and Webcast

Mereo BioPharma will hold a conference call today, March 21, at 8:30am ET. To participate by telephone, please dial [phone] in the U.S., or [phone] internationally, and ask for the Mereo BioPharma Group Conference Call. A live audio webcast of the call can be accessed through the Investors section of the Company’s website at www.mereobiopharma.com/investors. An archived replay of the webcast will be available on the Company’s website for two weeks following the live event.

About Mereo BioPharma

Mereo BioPharma is a biopharmaceutical company focused on the development of innovative therapeutics for rare diseases. The Company has developed a robust portfolio of clinical stage product candidates. The Company has two rare disease product candidates, setrusumab for the treatment of osteogenesis imperfecta (OI) and alvelestat for the treatment of severe Alpha-1 antitrypsin deficiency associated lung disease (AATD-LD) and Bronchiolitis Obliterans Syndrome (BOS). The Company’s partner, Ultragenyx Pharmaceutical, Inc., has initiated a pivotal Phase 2/3 pediatric study in young adults (5-25 years old) for setrusumab in OI and expects to initiate a study in pediatric patients (<5 years old) in the first half of 2023. The partnership with Ultragenyx includes potential milestone payments of up to $254 million and royalties to Mereo on commercial sales in Ultragenyx territories. Mereo has retained EU and UK commercial rights and will pay Ultragenyx royalties on commercial sales in those territories. Alvelestat has received U.S. Orphan Drug Designation for the treatment of AATD, Fast Track designation from the FDA, and positive data were recently reported from a Phase 2 proof-of-concept study in North America, Europe and the UK. In addition to the rare disease programs, Mereo has two oncology product candidates in clinical development. Etigilimab (anti-TIGIT) has completed enrollment in a Phase 1b/2 basket study evaluating its safety and efficacy in combination with an anti-PD-1 in a range of tumor types including three rare tumors and three gynecological carcinomas - cervical, ovarian, and endometrial; Navicixizumab, for the treatment of late line ovarian cancer, has completed a Phase 1 study and has