Mereo BioPharma Group plc
("Mereo" or the "Company" or the "Group")
Mereo BioPharma Announces Positive Results from the Safety Extension Study to the Phase 2b clinical trial of BGS-649 for the Treatment of Hypogonadotropic Hypogonadism in Obese Men
London, 17 December 2018 – Mereo BioPharma Group plc (AIM: MPH), a clinical stage, UK-based, biopharmaceutical company focused on rare and specialty diseases, announced positive data from the safety extension study to its phase 2b clinical trial of BGS-649 for the treatment of hypogonadotropic hypogonadism (HH) in men with a body mass index of over 30. BGS-649 is a once weekly oral aromatase inhibitor designed to restore a patient’s own testosterone to normal levels by inhibiting the conversion of testosterone to oestradiol. The Company previously reported positive headline data from the phase 2b clinical trial in March 2018, with the drug meeting primary and secondary endpoints with high statistical significance following 6 months treatment. The safety extension study enrolled 143 patients, with 88 patients completing the additional six months of treatment.
This safety extension study was designed to examine if BGS-649 resulted in a pre-specified reduction in bone mineral density (BMD) at 48 weeks following the initial 24 weeks treatment. The primary end point of this safety extension study was decrease in BMD. The study was successful in demonstrating that none of the doses of BGS-649 met the lower bound (95% confidence interval) of the pre-specified safety criterion of a greater than 3% reduction in lumbar spine BMD after 48 weeks of treatment. Consistent with this finding, none of the doses of BGS-649 met the secondary safety endpoint criterion of a greater than 3% reduction in bone mineral density in the hip (total or femoral neck). In addition, there was no shift into clinical categories of osteopenia or osteoporosis, with no evidence of development of new osteopenia.
Consistent with the top-line data announced by Mereo in March 2018, treatment with BGS-649 resulted in normalization of total testosterone levels in over 75% of subjects at all three doses tested at the end of the six months extension study period (this measure was the primary endpoint in the placebo-controlled portion of the trial). Similarly, normalization of testosterone in at least 90% of patients (a key secondary endpoint of the placebo-controlled portion of the trial) occurred at all three doses (versus at the two highest doses in the initial 6 months). All three doses also continued to meet all other secondary endpoints, including the improvement of testosterone luteinising hormone (LH) and follicle stimulating hormone (FSH) levels. The extension study continued to demonstrate a clear dose-response in both the primary and secondary endpoints. The total motile sperm count was not determined in this extension study and the company is continuing to analyse the data from the exploratory patient reported outcomes (PROs).
The adverse event profile in the extension study, where all patients received one of the three doses of BGS-649 for 6 months was similar to that seen in patients receiving the drug in the placebo controlled portion of the trial. There was an increased incidence of raised haematocrit levels in patients receiving BGS-649 and small increases in blood pressure at the two highest doses consistent with increasing testosterone.
Dr. Denise Scots-Knight, Chief Executive Officer of Mereo commented:
“We are pleased that the results of our six-month extension study reiterate the positive top-line results we announced earlier this year. The extension data provides further evidence of the potential of BGS-649. Following further data analysis in 1H 2019 we will confirm our plans for the late stage clinical development of this promising drug as we also consider potential partnerships.”
About the Phase 2b study and six-month extension study
The Phase 2b dose-confirmation study, which commenced in 2016, was a randomized, double-blind, placebocontrolled clinical trial assessing three different dosing regimens of BGS-649 in 271 obese men with HH. Following baseline assessment, patients were randomized to receive one of three weekly doses of BGS-649 or placebo for 24 weeks. The primary endpoint was normalization of total testosterone levels in greater than 75% of subjects after 24 weeks of treatment. Secondary measures included determining the impact of BGS-649 on the levels of testosterone LH and FSH, as well as normalization of total testosterone in greater than 90% of the subjects after 24 weeks of treatment. Exploratory end points included semen parameters and patient reported outcomes (PROs). At the end of the initial 24-week treatment period, patients had the option to enrol into a six-month safety extension study in which they received the same dose or in the case of placebo patients, were randomized to one of the three doses. Patients continued to be monitored for LH and FSH levels and bone mineral density. The Phase 2b safety extension study enrolled 143 patients, with 88 patients completing the six-month safety extension study.
About Hypogonadotropic Hypogonadism
Hypogonadotropic hypogonadism results from inadequate levels of testosterone. Symptoms associated with testosterone deficiency include reduced/loss of libido, erectile dysfunction, tiredness, fatigue, impaired physical endurance, loss of vitality, lack of motivation and mood disturbance. There are approximately seven million cases of HH in obese men in the US and approximately five million cases in Europe. Current therapies for HH involve direct replacement of testosterone administered by gel formulations applied to the skin, which risk transference to anyone in close contact, patches or intramuscular injections, which can be painful and inconvenient. Direct exogenous testosterone replacement can also impair male fertility by suppressing LH and FSH.
BGS-649 is a once a week oral treatment for HH in obese men, that restores a patient’s own testosterone. It is a novel aromatase inhibitor that inhibits conversion of the patients’ own testosterone to oestradiol, thereby increasing testosterone levels. BGS-649 is designed to be more convenient compared with current therapies and due to its mechanism of action restores normal testosterone production without the risk of supraphysiological levels or suppression of LH and FSH, thereby treating the symptoms of HH whilst maintaining or improving testicular function.
Mereo is a biopharmaceutical company focused on the development and commercialization of innovative therapeutics that aim to improve outcomes for patients with rare diseases. Mereo’s strategy is to selectively acquire product candidates that have already received significant investment from pharmaceutical companies and that have substantial preclinical, clinical and manufacturing data packages. In December 2018, Mereo announced the proposed combination of Mereo and OncoMed Pharmaceuticals Inc., with the transaction expected to close in the first half of 2019. Each of Mereo’s four product candidates has previously generated positive clinical data for Mereo’s target indication or in a related indication. Since inception Mereo has commenced large, randomized, placebo-controlled Phase 2 clinical trials for all four of the product candidates:
- BPS-804 for osteogenesis imperfecta (OI). The Company recently announced completion of enrolment with 112 adult patients in a Phase 2b dose ranging study with some initial data expected in the H1 2019 and top-line dose ranging data in late 2019. A pediatric Phase 3 study design has also been approved by the EMA. BPS-804 has orphan designation in the US and EU and has been accepted into the PRIME and Adaptive Pathways in EU;
- MPH-966 for alpha-1 antitrypsin deficiency (AATD). The Company recently announced first patient in in a Phase 2 dose ranging study in the US with data expected in late 2019;
- BCT-197 for acute exacerbations of COPD (AECOPD). The Company presented positive Phase 2 data at the American Thoracic Society in May, 2018; • BGS-649 for hypogonadotropic hypogonadism (HH). The Company announced positive top-line Phase 2b data in March 2018; and
- As at September 30, 2018 Mereo had (unaudited) total cash resources of approximately US$44.6 million.
For Further Enquiries
Mereo BioPharma Group plc
+44 (0)333 023 7319
Denise Scots-Knight, Chief Executive Officer
Richard Jones, Chief Financial Officer
Nominated Adviser and Joint Broker
Cantor Fitzgerald Europe
+44 (0)20 7894 7000
RBC Capital Markets
+44 (0)20 7653 4000
UK Public Relations Advisor to Mereo Biopharma
+44 (0)20 3727 1000
US Public Relations Advisor to Mereo Biopharma
+01 (0) 212 213 0006