D. Macut*a (Prof), M. Fleseriub (Prof), A. Drevalc (Prof), Y. Pokramovichc (Dr), I. Bondard (Prof), E. Isaevae (Dr), M. Molitchf (Prof), N. Leonovag (Dr), A. Havivh (Dr), N. Biermaszi (Prof), S. Melmedj (Prof), G. Raverotk (Prof), C. Strasburgerl (Prof)

a Faculty of Medicine, University of Belgrade, Belgrade, Serbia, Belgrade, SERBIA ; b Oregon Health & Science University, Portland, UNITED STATES ; c M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow, RUSSIAN FEDERATION ; d Novosibirsk State Medical University, Novosibirsk, RUSSIAN FEDERATION ; e Interregional Clinical Diagnostic Center, Kazan, RUSSIAN FEDERATION ; f Northwestern University Feinberg School of Medicine, Chicago, UNITED STATES ; g Antrium Multidisciplinary Medical Clinic, Barnaul, RUSSIAN FEDERATION ; h Chiasma, Ltd, Ness Ziona, ISRAEL ; i Leiden University Medical Center, Leiden, NETHERLANDS ; j Cedars-Sinai Medical Center, Los Angeles, UNITED STATES ; k Hospices Civils de Lyon, Bron, FRANCE ; l Charite-Universit√§tsmedizin, Campus Mitte, Berln, GERMANY

* djmacut@gmail.com

Background: In previous acromegaly studies, oral octreotide capsules (OOC) were initiated circa the time of the next scheduled injectable somatostatin receptor ligands (iSRL) dose. The MPOWERED phase 3 trial assessed maintenance of response to OOC versus iSRLs in patients with acromegaly who previously tolerated and responded to both therapies. Patients could start OOC any time after their last injection up to the time of next scheduled injection plus 3 days. The impact of earlier initiation of OOC on safety and efficacy has not been previously investigated.

Objective To describe clinical and safety outcomes based on the time since the last iSRL dose and initiation of OOC during the 26-week Run-in phase of MPOWERED.

Methods Eligibility criteria included age 18-75 years, acromegaly diagnosis, disease evidence, biochemical control (insulin-like growth factor I [IGF-I] <1.3 × upper limit of normal [ULN] and mean integrated growth hormone <2.5 ng/mL) at screening, and ≥6 months iSRL treatment. The Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ, a validated tool with 27 items in 6 domain scores for patient reported outcomes in acromegaly), was used collected data at baseline (reflecting outcomes on iSRLs) and end of Run-in (reflecting outcomes on OOC).

Results During the Run-in phase, OOC (administered to all patients) was initiated within or after 3 weeks of the last iSRL injection in 40 and 105 patients, respectively. Mean IGF-I values at baseline and end of Run-in were 0.9 and 1.1 × ULN in both groups. 28/40 (70%) and 67/105 (64%) of patients demonstrated biochemical control (IGF-I <1.3 × ULN) at end of Run-in. No significant differences were found in any Acro-TSQ domain scores between groups. There was no increase in reported safety issues with earlier initiation of OOC (1/40 [2.5%] patients discontinued OOC due to adverse events in this phase) versus those initiating OOC more than 3 weeks after their last injection (n=13/105, 12.4%).

Conclusions Earlier initiation of OOC was not associated with differences in biochemical control or quality of life measures in patients previously stable on iSRLs. No new or increased safety signals were identified with a shorter time to initiation of OOC.

The author has declared the following conflict(s) of interest:

  1. Prof Djuro P. Macut: Principle Investigator: (self) Amryt(fka Chiasma); Speaker: (self) Novartis, Novo Nordisk, Sanofi, Pfizer; Other: (self) member of the Executive Committee of the European Society of Endocrinology (ESE)
  2. Prof Maria Fleseriu: Consulting Fee: (self) Amryt (fka Chiasma), Ipsen, Ionis, Recordati, Pfizer; Research Investigator: (self) Amryt(fka Chiasma), Crinetics, Ionis, Recordati; Other: (self) Deputy Editor at EJE
  3. Prof Alexander Dreval: (self) Amryt(fka Chiasma)
  4. Dr Yulia Pokramovich: Research Investigator: (self) Amryt(fka Chiasma)
  5. Prof Irina Bondar: Research Investigator: (self) Amryt(fka Chiasma)
  6. Dr Elena Isaeva: Research Investigator: (self) Amryt(fka Chiasma)
  7. Prof Mark E. Molitch: Consulting Fee: (self) Corcept, Janssen, Merck,  Novo-Nordisk, Pfizer and Novartis; Grant Recipient: (self) Amryt(fka Chiasma), Crinetics, Ionis; Research Investigator (self): Bayer
  8. Dr Nina Leonova: Research Investigator: (self) Amryt(fka Chiasma)
  9. Dr Asi Haviv, Chiasma Ltd.., Ness Ziona, Israel: Employee: (self) Amryt(fka Chiasma)
  10. Prof Nienke Biermasz: Ad Board: (self) Recordati, Pfizer, Macro Registry; Grant: (self) Amryt(fka Chiasma)
  11. Prof Shlomo Melmed: Advisory Board Member: (self) Ionis, Crinetics; Consulting Fee: (self) Ipsen; Grant Recipient: (self) Pfizer
  12. Prof Gerald Raverot: Research Investigator: Amryt (fka Chiasma), Pfizer, Novartis; Speaker: Ipsen, Novartis, Pfizer, Recordati Rare Diseases; Consulting Fee:  Pfizer, Recordati Rare Diseases, Ipsen; Ad Board Member: Pfizer, Recordati Rare Diseases
  13. Prof Christian J. Strasburger: Advisory Board Member: (self) Sandoz, Ipsen, Recordati; Consulting Fee: (self) Ascendis, Amryt(fka Chiasma), NovoNordisk, Merck, Sandoz, Recordati; Speaker: (self) Ipsen, NovoNordisk, HRA-Pharma