Somatrogon©

Somatrogon^© COMPETITIVE ADVANTAGES

In 2014, Pfizer and OPKO entered into a worldwide agreement for the development and commercialization of Somatrogon^©. Under the agreement, OPKO is responsible for conducting the clinical program and Pfizer is responsible for registering and commercializing the product.

• New molecular entity (NME) that maintains natural native sequence of growth hormone
• Once weekly injection vs. current products requiring daily injections
• Human growth hormone is used for:
  • Growth hormone deficient children and adults
  • SGA, PWS, ISS
• Final presentation:
  • Refrigerated, liquid, non-viscous formulation
  • Disposable easy to handle pen injection device with thin needle and small injection volume
• Orphan drug designation in the U.S. and the EU for children and adults

Somatrogon^© PROGRAM STATUS

Phase 3 Pediatric Somatrogon^©

• Phase 3 study in naive growth hormone deficiency pediatric population was completed.

The study was conducted in over 20 countries. This study enrolled and treated 224 pre-pubertal, treatment-naive children with growth hormone deficiency.

• OPKO and Pfizer Announce Positive Phase 3 Top-Line Results for Somatrogon^© during Oct 2019.
• Achieved Primary Endpoint
  • Somatrogon^© was proven non-inferior to daily Genotropin® (somatropin) with respect to height velocity after 12 months
  • Height velocity at 12 months of treatment was higher in the Somatrogon^© group (10.12 cm/year) than in the somatropin group (9.78 cm/year)
• Secondary Endpoints Achieved
  • Change in height standard deviation scores at six and 12 months were higher with Somatrogon^© in comparison to somatropin
  • At six months, change in height velocity was higher with Somatrogon^© in comparison to somatropin
  • Somatrogon^© was generally well tolerated in the study and comparable to that of somatropin dosed once-daily with respect to the types, numbers and severity of the adverse events observed between the treatment arms
• Children completing this study had the opportunity to enroll in a global, open-label, multicenter, long-term extension study, in which they were able to either continue receiving or switch to Somatrogon^© Approximately 95% of the patients switched into the open-label extension study and received Somatrogon^© treatment

Phase 3 adults Somatrogon^© completed

• Primary endpoint of change in trunk fat mass from baseline to 26 weeks did not demonstrate a statistical significance between the Somatrogon^© treated group and placebo
• Completed post hoc outlier analysis in June 2017 to assess the influence of outliers on the primary endpoint results
• Analyses which excluded outliers showed a statistically significant difference between Somatrogon^© and placebo on the change in trunk fat mass: additional analyses that did not exclude outliers showed mixed results
• No safety concerns
• OPKO and Pfizer have agreed that OPKO may proceed with a pre-BLA meeting with FDA to discuss a submission plan
• OPKO plans to carry out an additional study in adults using a pen device

Pediatric Somatrogon^© registration study in Japan- expected to be completed in Q1 2020

• 44 patients, comparison of weekly Somatrogon to daily growth hormone.
• Same pen device, dosage and formulation used in global study.

Somatrogon^© Path to Approval

• BLA submission in US anticipated second half of 2020
  • Completion of analysis of immunogenicity and safety data from pivotal Phase 3 study and open label extension study
• Two abstracts accepted for oral presentation of data set at the Endo Society’s Annual Meeting in March 2020
  • “Somatrogon^© Growth Hormone in the Treatment of Pediatric Growth Hormone Deficiency: Results of the Pivotal Phase 3”
  • “Interpretation of Insulin-like Growth Factor (IGF-1) Levels Following Administration of Somatrogon^© (a long acting Growth Hormone-hGH-CTP)”
• MAA submission in Europe to follow upon completion of open label study demonstrating benefit and compliance with reduced treatment burden
  • Study expected to be completed in Q3 2020

References

Hershkovitz O, Bar-Ilan A, Guy R, et al. In vitro and in vivo characterization of MOD-4023, a long-acting carboxy-terminal peptide (CTP)-modified human growth hormone. Mol Pharm. 2016; 13:631–639 [PDF]

Strasburger CJ, Vanuga P, Payer J, et al. MOD-4023, a long-acting carboxy-terminal peptide-modified human growth hormone: results of a Phase 2 study in growth hormone-deficient adults. Eur J Endocrinol. 2017;176:283–294 [PDF]

Zelinska N, Iotova V, Skorodok J, et al. Long-acting CTP-modified hGH (MOD-4023): results of a safety and dose-finding study in GHD children. J Clin Endocrinol Metab. 2017;102:1578–1587 [PDF]

Fisher DM, Rosenfeld RG, Jaron-Mendelson M, et al. Pharmacokinetic and pharmacodynamic modeling of MOD-4023, a long-acting human growth hormone, in GHD Children. Horm Res Paediatr. 2017;87:324–332 [PDF]

Kramer W, Jaron-Mendelson M, Koren R, et al. Pharmacokinetics, Pharmacodynamics and Safety of a Long-Acting Human Growth Hormone (MOD-4023) in Healthy Japanese and Caucasian Adults. Clin Pharmacol Drug Dev. 2017 [in press]