Safety and efficacy of Ovaleap® (recombinant human follicle-stimulating hormone) for up to 3 cycles in infertile women using assisted reproductive technology: a phase 3 open-label follow-up to Main Study.
BACKGROUND
Ovaleap® (follitropin alfa), a recombinant human follicle-stimulating hormone intended for use in controlled ovarian stimulation in women undergoing assisted reproductive technologies (ART), showed therapeutic equivalence to Gonal-f® in a multinational, multicenter, randomized, controlled, assessor-blind phase 3 Main Study. The current study examined safety, including immunogenicity, and efficacy of Ovaleap® in an open-label, uncontrolled, follow-up treatment period of up to 2 additional treatment cycles in patients who did not become pregnant in the phase 3 Main Study.


METHODS
Patients with negative biochemical or clinical pregnancy in the phase 3 Main Study, regardless of treatment group (ie, Ovaleap® or Gonal-f®), were eligible to participate. Patients received Ovaleap® (Merckle Biotec GmbH, Ulm, Germany) for up to 2 additional cycles, administered using a reusable semi-automated pen device. The primary objective was the assessment of safety, including adverse events (AEs), ovarian hyperstimulation syndrome (OHSS), and anti-drug antibodies. Tolerability, patient satisfaction with the Ovaleap® pen device, and efficacy outcomes (as evaluated in the Main Study) were also assessed.


RESULTS
One hundred forty-seven patients were included in cycle 2, and 61 patients were included in cycle 3. In cycles 2 and 3, 10.9 % (16/147) and 6.6 % (4/61) of patients experienced treatment-emergent AEs (TEAEs), respectively. Three serious TEAEs (ie, appendicitis, OHSS, and borderline ovarian tumor) were reported and successfully resolved. The OHSS TEAE was the only OHSS reported in the study (0.7 % [1/147]). Positive findings on anti-drug antibody assays in 6 serum samples did not show neutralizing activity or clinical relevance in biochemical pregnancy rate. No hypersensitivity reaction occurred. Most patients reported "very good"/"good" local tolerability. All patients were "very confident"/"confident" about dose accuracy and correctness of the injection. They all found use of the pen "very convenient"/"convenient" and were all "very satisfied"/"satisfied" with the pen device. Efficacy outcomes were consistent with the phase 3 Main Study.


CONCLUSIONS
These findings further support the safety, including immunogenicity, and efficacy of Ovaleap® for stimulation of follicular development in infertile women undergoing ART. The findings support continued use of Ovaleap® for multiple cycles or a switch to Ovaleap® if pregnancy is initially not achieved with Gonal-f®.


BACKGROUND
EudraCT number: 2009-017674-20. Current controlled trials register number: ISRCTN74772901 .
Department of Gynecological Endocrinology and Reproductive Medicine, University of Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany. Thomas_Strowitzki@med.uni-heidelberg.de.
Thomas
T
Strowitzki
Centre for Reproductive Medicine, Cryobank, Poland.|Department of Gynaecology and Gynaecological Oncology, Medical University, Bialystok, Poland.
Waldemar
W
Kuczynski
Merckle GmbH, 89079, Ulm, Germany.
Arnd
A
Mueller
Merckle GmbH, 89079, Ulm, Germany.
Peter
P
Bias
D000328:Adult; D005260:Female; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D043373:Follicle Stimulating Hormone, Human / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy*; D016471:Ovarian Hyperstimulation Syndrome / Q000139:chemically induced; D010062:Ovulation Induction / Q000379:methods*; D017060:Patient Satisfaction; D011247:Pregnancy; D018873:Pregnancy Rate; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
D043373:Follicle Stimulating Hormone, Human; D011994:Recombinant Proteins; C571801:follitropin alfa; D005640:Follicle Stimulating Hormone
Assisted reproductive technology (ART); Follitropin alfa; Infertility; Ovaleap; r-hFSH