A Novel Reversible Albumin-Binding Growth Hormone Derivative Possesses a Promising Once-Weekly Treatment Profile in Aghd

Program: Late-Breaking Abstracts
Session: LBSU 0377-0378-Growth Hormone Signaling
Translational
Sunday, June 22, 2014: 1:00 PM-3:00 PM
Hall F (McCormick Place West Building)

Poster Board LBSU-0377
Michael H°jby Rasmussen1, Jurgita JanukonytÚ2, Marianne C Klose, MD3, Djordje Marina4, Mette H Tanvig5, Lene Finnerup Nielsen1, Charlotte H÷ybye, MD, PhD6, Marianne Andersen7, Ulla Feldt-Rasmussen, Professor, MD, DMSc8 and Jens Sandahl Christiansen, MD, FRCPI, Dr.Med.Sci.9
1Novo Nordisk, 2Aarhus University Hospital, 3Rigshospitalet , University of Copenhagen,, Koebenhavn Oe, Denmark, 4Rigshospitalet , University of Copenhagen,, 5Odense University Hospital, 6Karolinska University Hospital, Stockholm, Stockholm, Sweden, 7Odense University Hospital, Odense C, Denmark, 8Rigshospitalet , University of Copenhagen,, Copenhagen, Denmark, 9Aarhus University Hospital, Aarhus C, Denmark
Recombinant human GH (rhGH) replacement therapy in children and adults currently requires daily sc. injections for several years or lifelong, which maybe both inconvenient and distressing for patients. NNC0195-0092 is a reversible albumin-binding growth hormone derivative, developed with the aim of reducing clearance and as consequence of a reversible binding to circulating serum albumin prolonging the pharmacodynamic (PD) effect.

The trial was a randomised, open-labelled, active-controlled, multiple dose, dose-escalating, sequential dose group trial investigating the safety, tolerability, pharmacokinetic (PK) and PD of weekly NNC0195-0092 compared to once daily rhGH. Four (4) cohorts of 8 adults with GHD in each cohort were investigated (in total, 32 AGHD subjects). The subjects enrolled into the trial were on stable GH replacement therapy, either male or female with a BMI between 18.0 to 35.0 kg/m2, age 20 to 70 years, Fourteen days before being randomized the AGHD subjects discontinued their GH replacement therapy. Four escalating doses of NNC0195-0092 were tested; 0.02, 0.04, 0.08 and 0.12 mg kg/week and in each dose-group 8 AGHD subjects were dosed with a subcutaneous administration of NNC0195-0092 (n=6) or daily rhGH (n=2). After 1st and 4th dosing at each dose level the pharmacokinetics and PD (IGF-I, IGFBP-3) were evaluated.

Multiple doses of NNC0195-0092 administered sc. to AGHD subjects were well tolerated at all doses investigated, with no serious safety issues identified. No positive test results for anti NNC0195-0092 antibodies, anti hGH antibodies, or local tolerability issues were observed at any dose level tested. A significant dose-dependent IGF-I response was induced, with elevated IGF-I levels at all dose levels of NNC0195-0092 investigated (0.02, 0.04, 0.08, 0.12 mg/kg). The IGF-I and IGFBP-3 levels were significantly greater for the 0.12mg/kg dose compared to rhGH and 0.02−0.08 mg/kg doses based on comparison of AUC0-168h and Cmax. A clinically relevant IGF-I response was induced by doses up to 0.08 mg/kg.

In conclusion, multiple dosing of NNC0195-0092 administered sc. to adult patients with GHD was well tolerated at all doses investigated. No antibodies or local tolerability issues were observed at any dose level tested. A clear dose-dependent PD response was observed with elevated IGF-I levels at all dose levels. The IGF-I profiles indicate that NNC0195-0092 possesses a very promising sustained once-weekly treatment profile in AGHD.

Disclosure: MHR: Employee, Novo Nordisk. JJ: Researcher, Novo Nordisk. LFN: Employee, Novo Nordisk. CH: Coinvestigator, Novo Nordisk. MA: Coinvestigator, Novo Nordisk. UF: Principal Investigator, Novo Nordisk, Principal Investigator, Novartis Pharmaceuticals, Speaker, Pfizer, Inc., Speaker, Novo Nordisk, Speaker, Ipsen, Speaker, Novartis Pharmaceuticals, Advisory Group Member, Pfizer, Inc.. JSC: Research Funding, Novo Nordisk, Board Member, Novo Nordisk, Board Member, The name is Merck Serono, lectures, Novo Nordisk, lectures, Pfizer, Inc., fees, Eli Lilly & Company. Nothing to Disclose: MCK, DM, MHT

*Please take note of The Endocrine Society's News Embargo Policy at https://www.endocrine.org/news-room/endo-annual-meeting

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