GHRYVELIN (macimorelin acetate) - Diagnosis of growth hormone (GHD) deficiency
Opinions on drugs -
Posted on
Apr 12 2023
Reason for request
Inclusion
First assessment.
Key points
Favourable opinion on reimbursement under “this medicinal product is for diagnostic use only. GHRYVELIN is indicated for the diagnosis of growth hormone (GHD) deficiency in adults.“
What therapeutic improvement?
No improvement in management strategy.
Role in the care pathway?
In view of its advantages in terms of administration taken orally as a single dose and of the reduced constraints for the patient post-administration (in terms of number of blood samples necessary, monitoring, tolerance), but insofar as the available clinical data do not allow its preferment relative to the insulin tolerance test (ITT, reference test), GHRYVELIN (macimorelin acetate) is an option for the diagnosis of growth hormone deficiency (GHD) in adults, in the same way as the ITT.
Clinical Benefit
Moderate
The clinical benefit provided by GHRYVELIN (macimorelin acetate) is moderate in the MA indication.
Clinical Added Value
no clinical added value
In view:
of the absence of demonstration of the equivalence of GHRYVELIN (macimorelin ace-tate) compared to the ITT reference test in the diagnosis of GHD in adults, in the study AEZS-130-052 which randomised 157 patients likely to suffer from GHD or healthy controls. In this study, the macimorelin stimulation test did not show sufficient agreement. The performance of the macimorelin test could not be judged acceptable as the lower limit of the two-sided 95% confidence interval was <70 % for one of the 2 co-primary endpoints, namely the positive percentage agreement.
of the fact that the validity of GHRYVELIN (macimorelin acetate) was not demonstrated in the AEZS-130-047 study conducted in 80 patients with GHD or controls. In fact, the lower limit of the 99% CI of the ASC of the ROC curve, obtained by "boot-strapping" data from 10,000 samples, 83.5%, was not compliant with the current criterion of ≥ 85 % for this parameter. The methodological quality of this study was limited, particularly because of numerous amendments and post-hoc analyses,
of the tolerance profile of GHRYVELIN (macimorelin acetate) marked by dysgeusia, fatigue and nausea, favourable compared to the comparator ITT in the AEZS-130-052 study. However, GHRYVELIN (macimorelin acetate) causes a lengthening of almost 11 ms of the corrected QT interval (QTc) the mechanism of which is unknown,
of the absence of a gold standard in the diagnosis of GHD in adults,
the Committee considers that GHRYVELIN (macimorelin acetate) provides no clinical added value (CAV V) compared to the insulin tolerance test (ITT).
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