The MPOWERED Phase 3 Trial : Oral Octreotide Outcomes based on IGF-I Response Criteria

M. Fleseriu*a (Prof), A. Drevalb (Prof), Y. Pokramovichb (Dr), I. Bondarc (Prof), E. Isaevad (Dr), M. Molitche (Prof), D. Macutf (Prof), N. Leonovag (Dr), G. Raveroth (Prof), A. Havivi (Dr), N. Biermaszj (Prof), C. Strasburgerk (Prof), S. Melmedl (Prof)

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

* fleseriu@ohsu.edu

Background

The MPOWERED study evaluated the efficacy and safety of oral octreotide capsules (OOC) versus injectable somatostatin receptor ligands (iSRLs, octreotide or lanreotide) in patients with acromegaly previously tolerating and responding to both. Here, we assessed the proportion of patients maintaining or improving biochemical response from baseline to the end of the run-in phase (Week 26) and the start to the end of the randomized control treatment (RCT) phase (Week 26-62) of MPOWERED based on categorization of insulin-like growth factor I (IGF-I) values.

Objective

To assess biochemical response during the phases of MPOWERED using different IGF-I thresholds.

Methods

Participants were 18-75 years, had an acromegaly diagnosis, disease evidence, biochemical control (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. During the run-in phase, all patients received OOC (40 mg/day, optional titration to 60 or 80 mg/day). Thereafter, eligible patients were randomized to receive OOC or iSRLs (same dose and interval before enrolment) in the RCT phase.

Results

At Week 26, 93/136 participants (68%) maintained baseline IGF-I <1.3 × ULN, while 61/98 participants (62%) entering the run-in phase with IGF-I ≤1.0 × ULN maintained this response. Reduction of IGF-I to ≤1.0 × ULN occurred in 7/48 (15%) and 1/10 (10%) participants who entered the run-in phase with IGF-I >1.0 × and ≥1.3 × ULN, respectively. During the RCT phase, 46/49 (94%) and 35/37 (95%) participants receiving OOC and iSRL therapy, respectively, maintained IGF-I <1.3 × ULN. Improvement of IGF-I levels from ≥1.3 to <1.3 × ULN was observed in 4/6 (67%) of OOC participants. Maintenance of IGF-I <1.0 × ULN occurred in 30/37 (81%) and 25/29 (86%) of participants receiving OOC and iSRLs from the start to the end of the RCT phase.

Conclusions

Using different IGF-I thresholds, maintenance of response was observed with OOC during the run-in phase of MPOWERED, consistent with previous studies using stringent response definitions. Biochemical response was comparable between the OOC and iSRL groups during the RCT phase regardless of the threshold used.

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

  1. 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
  2. Prof Alexander Dreval: (self) Amryt(fka Chiasma)
  3. Dr Yulia Pokramovich: Research Investigator: (self) Amryt(fka Chiasma)
  4. Prof Irina Bondar: (self) Amryt(fka Chiasma)
  5. Dr Elena Isaeva: (self) Amryt(fka Chiasma)
  6. Prof Mark E. Molitch: (self) Amryt(fka Chiasma), Crinetics, Ionis; Research Investigator (self): Bayer
  7. 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)
  8. Dr Nina Leonova: Research Investigator: (self) Amryt(fka Chiasma)
  9. 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
  10. Dr Asi Haviv, Chiasma Ltd.., Ness Ziona, Israel: Employee: (self) Amryt (fka Chiasma)
  11. Prof Nienke BiermaszAd Board: (self) Recordati, Pfizer, Macro Registry; Grant: (self) Amryt(fka Chiasma)
  12. 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
  13. Prof Shlomo Melmed: Advisory Board Member: (self) Ionis, Crinetics; Consulting Fee: (self) Ipsen; Grant Recipient: (self) Pfizer