TREATMENTS FOR HEMOPHILIA A
The present disclosure relates generally to treatments for hemophilia A using a swallowable device containing Factor VIII, wherein the device is structured and formulated to deliver therapeutically effective amounts of Factor VIII into the peritoneum and achieve desired pharmacokinetic and therapeutic results.
1 . A method of treating hemophilia A, comprising orally administering, to a subject with hemophilia A, a swallowable device containing a payload formed from, or containing, a composition comprising Factor VIII (FVIII), wherein the device is structured to deliver the FVIII into a peritoneal cavity of the subject, wherein the administering is at a frequency selected from twice every day, once every day, once every two days, and once every three days.
2 . A method of treating hemophilia A, comprising orally administering, to a subject with hemophilia A, a swallowable device containing a payload formed from, or containing, a composition comprising Factor VIII (FVIII), wherein the device is structured to deliver the FVIII into a peritoneal cavity of the subject, wherein the device contains a dose of FVIII of from about 30 IU/kg to about 300 IU/kg.
3 . A method of treating hemophilia A, comprising orally administering, to a subject with hemophilia A, a swallowable device containing a payload formed from, or containing, a composition comprising Factor VIII (FVIII), wherein the device is structured to deliver the FVIII into a peritoneal cavity of the subject, wherein the method is effective to protect the subject from breakthrough bleeding for at least 72 hours and up to 120 hours.
4 . The method of claim 3 , wherein the breakthrough bleeding is spontaneous bleeding.
5 . The method of claim 2 , wherein the device is administered daily.
6 . The method of claim 1 , wherein the device contains a dose of FVIII of from about 1,000 IU to about 12,000 IU.
7 . The method of claim 6 , wherein the device contains a dose of FVIII of 3,000 IU, 6,000 IU, or 9,000 IU.
8 . The method of claim 1 , wherein the composition comprising FVIII is a dry composition filled in a hollow, biodegradable microneedle constituting the solid tissue penetrating member.
9 . The method of claim 1 , wherein the FVIII is a long-circulating form of FVIII.
10 . The method of claim 1 , wherein the FVIII is a recombinant human PEGylated FVIII.
11 . The method of claim 2 , wherein the method comprises administering the device to the subject at a frequency selected from once every 2 days, once every 3 days, once every 4 days, once every 5 days, once every 6 days, and once every 7 days.
12 . The method of claim 1 , wherein the dose of FVIII is selected from about 75 IU/kg, about 100 IU/kg, about 125 IU/kg, about 150 IU/kg, about 175 IU/kg, about 200 IU/kg, about 225 IU/kg, about 250 IU/kg, and about 275 IU/kg.
13 . The method of claim 1 , wherein the dose of FVIII is from about 50 IU/kg to about 250 IU/kg, from about 50 IU/kg to about 200 IU/kg, from about 50 IU/kg to about 150 IU/kg, or from about 50 IU/kg to about 100 IU/kg.
14 . The method of claim 1 , wherein the method is effective in maintaining one or both of hemostasis and normalized coagulopathy in the subject for a period of time selected from at least 24 hours, at least 36 hours, at least 48 hours, at least 60 hours, at least 72 hours, at least 84 hours, or at least 96 hours, and up to 120 hours.
15 . The method of claim 1 , wherein the method is effective to protect the subject from one or both of breakthrough bleeding and spontaneous bleeding for a period of time selected from at least 24 hours, at least 36 hours, at least 48 hours, at least 60 hours, at least 72 hours, at least 84 hours, or at least 96 hours, and up to 120 hours.
16 . The method of claim 1 , wherein the method is effective to maintain FVIII at therapeutic levels in the subject for an equal or longer period of time than intravenous administration of an equal dose of FVIII.
17 . The method of claim 1 , wherein the payload is in the form of a solid tissue penetrating member structured to penetrate an intestinal wall of the subject and/or be inserted into a peritoneal cavity of the subject after oral ingestion of the swallowable device.
18 . The method of claim 1 , wherein the device comprises multiple payloads or doses of FVIII.
19 . The method of claim 18 , wherein the device is structured to deliver one or more payloads or doses into the peritoneal cavity of the subject at different times.
20 . The method of claim 18 , wherein the device comprises 2, 3, 4, or 5 or more payloads or doses of FVIII.
21 . The method of claim 1 , wherein the swallowable device is comprised within a capsule.
22 - 24 . (canceled)