Abstract Number: OC 48.4
Meeting: ISTH 2021 Congress
Background: Hemophilia A patients currently face a lifelong burden of frequent injections. An oral FVIII therapy could greatly improve compliance and quality of life for these patients. We have developed an orally ingestible robotic pill (oral RP) which protects the drug payload (sealed inside a hollow, dissolvable needle) from digestion in the GI tract and auto-injects it into the wall of the small intestine which is insensate to sharp stimuli.
Aims: To evaluate safety and efficacy of FVIII delivered via the orally ingestible RP in hemophilia A dogs.
Methods: The oral RP containing PEGylated human recombinant FVIII (2,650 IU) was administered to an awake 16.8 kg hemophilia A dog (N=1). Serial blood samples were collected up to 7 days to assess changes in pharmacokinetic (PK) parameters (FVIII antigen and activity) and pharmacodynamic (PD) parameters (whole blood clotting time, thromboelastography and activated partial thromboplastin time (aPTT)). Data were compared to those from another hemophilia A dog (N=1) which received a comparable dose of PEGylated FVIII via direct intraperitoneal injection.
Results: Both oral RP and direct intraperitoneal injection normalized the coagulopathy for up to 3 days (Figure 1A) with concomitant changes in plasma FVIII antigen and activity (Figure 1B). The time-course and pattern of PK and PD changes with both the oral RP and manual intraperitoneal injection of FVIII were similar. No AEs were noted throughout the study period.
Conclusions: A single dose of FVIII delivered via the oral RP restored markers of hemostasis in a dog model of hemophilia A for 3 days. PK-PD analyses suggest that the RP delivered FVIII payload in the peritoneal space. These data provide an early preclinical proof-of-concept of the potential to replace frequent intravenous injections of FVIII with an orally ingestible therapy for hemophilia A patients.
This is a collaborative research study funded by Takeda Pharmaceuticals International AG (TPIZ).
To cite this abstract in AMA style:Hashim MA, Yamaguchi A, Vo AT, Dhalla AK, Syed B, Fung LC, Salgotra V, Dasari A, Schrenk G, Zoechling O, Sexton D, Allen G, Long CT, Merricks EP, Imran M, Nichols TC. Orally Delivered Factor VIII Restores Hemostasis in a Hemophilia A Dog [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/orally-delivered-factor-viii-restores-hemostasis-in-a-hemophilia-a-dog/. Accessed May 16, 2022.
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