EXHIBIT 99.1
Published on September 23, 2019
Long-Term Safety of a Once-Weekly Somatrogon (hGH-CTP): 4-Year Results of a Phase 2 Extension Study in Children with Growth Hormone Deficiency Nataliya Zelinska1, Yulia Skorodok2, Oleg Malievsky3, Violeta Iotova4, Ron G. Rosenfeld5, Zvi Zadik6, Shelly Vander7, and Aleksandra Pastrak8 1Ukrainian Children Specialized Clinical Hospital, Kyev; 2St. Petersburg State Pediatric Medical University, St. Petersburg; 3Bashkir State Medical University, Ufa; 4UMHAT, Varna; 5Oregon Health & Science University, Oregon, USA; 6Kaplan Medical Center, Rehovot, Israel; 7OPKO Biologics, Kiryat Gat, Israel; 8OPKO Health, Miami. TEAEs > 5% of subjects All (N=48) TEAEs > 5% of subjects All (N=48) BACKGROUND U. resp. tract infection 13 (27.1) Ear infection 4 (8.3) Once-daily growth hormone (GH) therapy is an effective treatment for children with Bronchitis 9 (18.8) Nasopharyngitis 4 (8.3) growth hormone deficiency (GHD), but a decrease in compliance with prolonged Rhinitis 5 (10.4) treatment can reduce the treatment benefits. Somatrogon, also known as MOD-4023, Parameter, Mean (SD) OLE Y1 OLE Y2 OLE Y3/Y4 is a long-acting recombinant protein consisting of human growth hormone (hGH) and N 45 43 40 three copies of C-terminal peptide (CTP). It is a new molecular entity with receptor HbA1c, % Mean 5.12 (0.282) 5.16 (0.309) 5.17 (0.343) binding properties and a mechanism of action analogous to hGH. A once-weekly Fasting glucose, N 44 42 40 somatrogon (hGH-CTP), is being developed to reduce the treatment burden of daily mmol/L Mean 4.65 (0.598) 4.45 (0.433) 4.68 (0.447) dosing for children and caregivers and potentially improve compliance and long-term efficacy [1]. Anti-Somatrogon Overall OLE Y1 OLE Y2 OLE Y3 Figure 1. Long-acting CTP-hGH protein antibody, n (%) (N=48) (N=48) (N=44) (N=43) Anti-somatrogon Ab 17 (35.4) 12 (25.0) 11 (25.0) 11 (25.6) CTP Neutralizing Ab 0 0 0 0 CTP – a natural peptide created during evolution to enhance the half-life of hCG • The safety and tolerability from the OLE study were comparable to that observed in the 12-month Phase 2 study [2] and the reported safety profile of daily r-hGH. OBJECTIVES hGH Most AEs were of mild severity (75.8%) and no local tolerability issues were identified. The objective of the open-label extension (OLE) Phase 2 study was to demonstrate • There were 3 non-related serious AEs, and one probably related serious AEs of the long-term impact of once-weekly somatrogon treatment beyond the initial 12 exacerbation of thoracic scoliosis that led to discontinuation. months of the primary study. Key objectives of this report included evaluation of safety, local tolerability, growth outcome and immunogenicity in patients treated with • There were no changes in HbA1c, fasting glucose, or insulin over the 4 years of somatrogon for a period of up to 4 years in the OLE. treatment in the OLE. • Low titers of anti-somatrogon antibodies were detected in 17 subjects, of which 3 METHODS subjects had transient antibodies. All samples were negative for neutralizing Ab. The OLE phase 2 study was a continuation of a randomized 12-month study that RESULTS: Efficacy investigated the efficacy, safety, and tolerability of 3 dose levels of somatrogon, administered weekly (0.25, 0.48, or 0.66 mg/kg/week) compared to daily r-hGH Annualized HV (cm/year ± SD) Height SDS (Z ± SD) (Genotropin® 0.034 mg/kg/day) in pre-pubertal pediatric patients with GHD [2]. 16 0.0 Forty-eight children with GHD that completed the main Phase 2 study continued in 14 -1.27 12 -1.0 (N=38) the OLE. Subjects who were randomized to somatrogon in the main study continued 11.93 -1.60 10.96 (N=43) with the same dose of somatrogon; subjects who were originally assigned to daily 10 10.44 -2.06 (N=48) Genotropin® were randomly re-assigned toCT one of the three somatrogon dose levels. 8 8.81 -2.0 7.73 7.54 -2.61 7.18 7.12 Following the first 12-months of treatment in the OLE all subjects were transitioned 6 (N=41) to 0.66 mg/kg/week. 4 -3.0 Subjects were treated with somatrogon (frozen vial) for up to 4 years until transfer to 2 0.25 mg/kg (N=13) 0.48 mg/kg (N=15) 0.66 mg/kg (N=13) 0.25 mg/kg (N=15) 0.48 mg/kg (N=17) 0.66 mg/kg (N=14) 0.66 mg/kg (N=44) 0.66 mg/kg (N=38) a somatrogon pen device. Forty subjects (83%) are continuing in OLE on pen device 0 -4.0 (Figure 2). Top line results for up to 4 years of treatment in the OLE are reported. Main Study Open Label Extension OLE OLE Main OLE OLE OLE Year 1 Year 1 Year 2 Year 3 Year 1 Year 1 Year 2 Year 3 Figure 2. Study design (ClinicalTrials.gov: NCT01592500) End of OLE 1st Transition to Parameter, Mean (SD) OLE Y1 OLE Y2 OLE Y3 Final Analysis Year OLE Pen Device N 43 41 38 Cohort 1 IGF-1 SDS, Z 0.25 mg/kg 0.25 mg/kg Mean 0.64 (0.956) 0.65 (1.082) 1.05 (0.819) Somatrogon Cohort 2 0.48 mg/kg 0.48 mg/kg 0.66 mg/kg 0.66 mg/kg (Weekly) • Mean annualized HV over 3 years in the OLE shows that long-term somatrogon Cohort 3 treatment resulted in sustained growth rate. Height SDS values showed height 0.66 mg/kg 0.66 mg/kg R Randomization normalization over time. • IGF-1 and IGF-binding protein-3 (IGFBP-3) levels remained within the normal range Genotropin Cohort 4 0.034 mg/kg R (Daily) with ongoing somatrogon therapy. • Subjects that had developed non-neutralizing Abs demonstrated similar annualized Main study Open-label OLE on pen until (1 year) extension (OLE) market approval HV (cm/year) to subjects with no detectable Abs [8.43 (1.03) vs. 7.85 (1.66), 7.17 (1.31) vs. 7.19 (1.25), and 6.71 (1.19) vs. 7.36 (1.56)]; and height SDS [-2.31 (1.22) RESULTS: Demographics at the Start of Open Label Extension vs. -1.98 (0.70) , -1.71 (1.10) vs. -1.54 (0.63), and -1.47 (1.12) vs. -1.15 (0.80) for OLE year 1, 2, and 3, respectively]. All (N=48) All (N=48) CONCLUSION Mean age (SD), years 7.65 (2.104) Mean weight (SD), kg 20.39 (5.150) Gender, male (%) 32 (66.7) Mean height (SD), cm 112.6 (11.07) • Somatrogon treatment demonstrated a favorable safety profile and local tolerability Race, white (%) 45 (93.8) Mean BMI (SD), kg/m2 15.82 (1.740) after four years of dosing in GHD pediatric subjects Pubertal status Tanner I (%) 47 (97.9) Mean IGF-1 SDS (SD), Z 0.03 (1.176) • Serum IGF-1 SDS values were maintained within the normal range, and a growth RESULTS: OLE Safety Years 1 to 4 rate comparable to that reported for daily hGH was observed • Low titers of non-neutralizing Abs did not affect growth parameters and IGF-1 levels Treatment-emergent adverse events (TEAEs) All subjects (N=48), n (%) [AEs] Any TEAEs 38 (79.2) [190] REFERENCES Serious TEAEs 3 (6.3) [4] TEAEs related to study drug 4 (8.3) [11] 1. Calo D et al. Precis Med 2015, (2) e989: 1-8 TEAEs leading to study discontinuation 1 (2.1) [1] 2. Zelinska N et al. J. Clin. Endocrin. Metab. 2017, (102) 1578-1587