Human chorionic gonadotropin(IBSA)

Treatments that aid inflammation resolution, immune tolerance, and epithelial repair may improve outcomes beyond high-dose corticosteroids and other broad immunosuppressants for life-threatening acute graft-versus-host disease (aGVHD). We studied the addition of urinary-derived human chorionic gonadotropin/epidermal growth factor (uhCG/EGF; Pregnyl; Organon, Jersey City, NJ) to standard aGVHD therapy in a prospective Phase II clinical trial (ClinicalTrials.gov identifier NCT02525029). Twenty-two patients with Minnesota (MN) high-risk aGVHD received methylprednisolone 48 mg/m²/day plus 2000 units/m² of uhCG/EGF s.c. every other day for 1 week. Patients requiring second-line aGVHD therapy received uhCG/EGF 2000 to 5000 units/m² s.c. every other day for 2 weeks plus standard of care immunosuppression (physician's choice). Responding patients were eligible to receive maintenance doses twice weekly for 5 weeks. Immune cell subsets in peripheral blood were evaluated by mass cytometry and correlated with plasma amphiregulin (AREG) level and response to therapy. Most patients had stage 3-4 lower gastrointestinal tract GVHD (52%) and overall grade III-IV aGVHD (75%) at time of enrollment. The overall proportion of patients with a response at day 28 (primary endpoint) was 68% (57% with complete response, 11% with partial response). Nonresponders had higher baseline counts of KLRG1⁺ CD8 cells and T cell subsets expressing TIM-3. Plasma AREG levels remained persistently elevated in nonresponders and correlated with AREG expression on peripheral blood T cells and plasmablasts. The addition of uhCG/EGF to standard therapy is a feasible supportive care measure for patients with life-threatening aGVHD. As a commercially available, safe, and inexpensive drug, uhCG/EGF added to standard therapy may reduce morbidity and mortality from severe aGVHD and merits further study.

Exogenous human chorionic gonadotropin (hCG) acts on the final phase of the follicle maturation. Choriomon^®, a highly purified hCG formulation, is approved in many European and extra-European countries for the induction of ovulation after stimulation of follicular development. The present study compares hCG bioavailability of Choriomon^® (Test product) versus a recombinant hCG preparation (Ovitrelle^®; Reference product).

In this randomized, two-way cross-over study, 26 healthy women received a single dose of Choriomon^® (10,000 IU) and Ovitrelle^® (250 µg; 6500 IU) by subcutaneous injection. hCG was determined in serum up to 192 h post-dose. Dose-normalized peak concentration (C_max) and area under the concentration-time curve up to the time of the last quantifiable concentration (AUC_0-t) and extrapolated to infinity (AUC_0-∞) were calculated and compared between the two treatments.

Serum hCG concentrations increased rapidly with a very similar pharmacokinetic curve for the two products. The test/reference geometric means ratio (GMR) for AUC_0-t and AUC_0-∞ corresponded to 121.31 and 119.81%, and the upper limits of the 90% confidence intervals (CIs) (130.21% and 128.51%, for AUC_0-t and AUC_0-∞, respectively) exceeded the 125% bioequivalence threshold. C_max GMR was 146.89%, indicating a rate of hCG absorption approximately 50% greater for the test product (90% CI 132.30-163.10). Half-life (t_1/2) was very similar (36.77 ± 5.11 h and 38.63 ± 6.08 h), whereas time to achieve C_max (t_max) significantly differed, with median values of 16 h and 24 h for Choriomon^® and Ovitrelle^®, respectively, (p = 0.0023).

The differences between Choriomon^® and Ovitrelle^® pharmacokinetic parameters can be ascribed to the different raw source of the products and are reflected in the approved dose regimens of the two hCG formulations. The observed lack of bioequivalence between the two compounds at the given doses is not clinically relevant, as results from Phase III studies indicated similar clinical efficacy and safety. The safety data are in line with the known safety profile of the two products.

NCT03735030.