On November 7, 2019, the FDA granted approval of Giskit B.V.’s ExEm® Foam (air polymer-type A) intrauterine foam, “an ultrasound contrast agent indicated for sonohysterosalpingography to assess fallopian tube patency in women with known or suspected infertility.” Key findings from the FDA’s Multi-Discipline Review, Other Review(s), and package insert:
Efficacy was demonstrated in four adequate and well-controlled studies (van Schoubroeck et al. 2013; Ludwin et al. 2017a; Piccioni et al. 2017; Riganelli et al. 2018), which were not pooled together for analysis. Two studies (Dreyer et al. 2015; Rosic et al. 2018) provided supportive evidence. The Dreyer and Rosic studies were considered supportive because the studies’ target populations were women who underwent tubal occlusion for sterilization or treatment of hydrosalpinx. However, there was poor generalizability of those findings to women with known infertility issues. “The primary sources of clinical evidence for safety came from published literature reporting ExEm Foam kit use and the pharmacovigilance database from the foreign postmarketing experience.”
ExEm Foam is marketed in several countries, including in the European Union since 2009. For a complete review of safety, the applicant reviewed its postmarket surveillance and reporting system—it disclosed voluntary reports in its submission.
The FDA’s safety database included:
What was done
- published studies on ExEm Foam use;
- postmarketing experience;
- comparisons to approved contrast agents for hysterosalpingography (HSG);
- safety profile of cleared devices for hysterosalpingo-contrast sonography using saline and air; and
- safety profile of a gel used as a coupling agent.
The applicant reviewed its postmarket surveillance and reporting system for ExEm Foam, which it has maintained since the initial European Union approval. The applicant disclosed 12 voluntary reports; none of the reports involved serious adverse events, or were related to fertility, pregnancy, or lactation. The complaints were related to side effects associated with the method/procedure, such as pain and vasovagal discomfort, not to ExEm Foam itself or its components.
(Note that the Administrative and Correspondence Documents
reveal July 2017 feedback from the FDA: “The meeting package lacks a detailed summary of the postmarketing experience for ExEm Foam and a description of the methods of postmarketing safety surveillance in the countries where the product is marketed. Provide these data and other information in your next submission.”)
Based on the published studies and postmarketing experience, ExEm Foam “does not appear to pose additional concerns beyond the risks already expected with sono-HSG or HSG.” A patient is unlikely to experience an adverse reaction to ExEm Foam or its components.
In the package insert, the FDA caveats that “because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure [and gynecologic infections].”
van Schoubroeck, D, T Van den Bosch, C Meuleman, C Tomassetti, T D'Hooghe, and D Timmerman, 2013, The use of a new gel foam for the evaluation of tubal patency, Gynecol Obstet Invest, 75(3):152-156.
Ludwin, I, A Ludwin, M Wiechec, A Nocun, T Banas, P Basta, and K Pitynski, 2017a, Accuracy of hysterosalpingo-foam sonography in comparison to hysterosalpingo-contrast sonography with air/saline and to laparoscopy with dye, Hum Reprod, 32(4):758-769.
Piccioni, MG, L Riganelli, V Filippi, E Fuggetta, V Colagiovanni, L Imperiale, J Caccetta, PB Panici, and MG Porpora, 2017, Sonohysterosalpingography: Comparison of foam and saline solution, J Clin Ultrasound, 45(2):67-71.
Riganelli, L, A Casorelli, J Caccetta, L Merlino, M Mariani, D Savone, A Carrone, S Franceschetti, C Aragona, D Pietrangeli, A Aragona, O Capri, and MG Piccioni, 2018, Ultrasonography reappraisal of tubal patency in assisted reproduction technology patients: Comparison between 2D and 3D-sonohysterosalpingography. A pilot study, Minerva Ginecol, 70(2):123-128.
Dreyer, K, PG Hompes, and V Mijatovic, 2015, Diagnostic accuracy of hysterosalpingo-foamsonography to confirm tubal occlusion after Essure(R) placement as treatment for hydrosalpinges, Reprod Biomed Online, 30(4):421-425.
Rosic, M, B Zegura, and S Vadnjal Donlagic, 2018, Use of hysterosalpingo-foam sonography for assessment of the efficacy of Essure hysteroscopic sterilization, J Ultrasound Med, 37(8):1929- 1935.