Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c

• US 9,889,085 B1
• Filed: 09/30/2015
• Issued: 02/13/2018
• Est. Priority Date: 09/30/2014
• Status: Active Grant

• Current Assignee: Intarcia Therapeutics, Inc.
• Original Assignee: Intarcia Therapeutics, Inc.
• Inventors: Alessi, Thomas R., Baron, Michelle
• Primary Examiner(s): Chandra, Gyan
• Application Number:
  US14/871,420
• Time in Patent Office: 867 Days
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: G01N 2333/805 Haemoglobins; Myoglobins
• CPC Class Codes: G01N 2800/042 Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/721 Haemoglobin

Abstract

The present invention is directed to treatments for a disease or condition, in a subject in need thereof, that provide alternatives to treatment by injection that give, relative to treatment by injection, improved treatment outcomes, 100% treatment compliance, reduced side effects, and rapid establishment and/or termination of substantial steady-state drug delivery. The method includes providing continuous delivery of a drug from an implanted osmotic delivery device, wherein substantial steady-state delivery of the drug at therapeutic concentrations is achieved within about 7 days after implantation of the osmotic delivery device in the subject and the substantial steady-state delivery of the drug from the osmotic delivery device is continuous over a period of at least about 3 months. In one embodiment, the present invention is directed to treatment of type 2 diabetes mellitus using insulinotrophic peptides. In embodiments, a subject has a baseline HbA1c % of greater than 6.5% or 10.0%.

Claims

1. A method of treating type 2 diabetes mellitus in a subject having a baseline hemoglobin A1c (HbA1c) % of greater than 10.0% comprising providing the subject a continuous delivery of a dose of at least 20 mcg/day of an exenatide from an osmotic delivery device, wherein the substantial steady-state delivery of the exenatide from the osmotic delivery device is continuous over an administration period of at least about 1 month, wherein the method produces a decrease in the subject'"'"'s HbA1c % of at least 2% after implantation of the osmotic delivery device in the subject, relative to the subject'"'"'s baseline HbA1c %, and wherein the decrease in the subject'"'"'s HbA1c % is achieved within 13 weeks after implantation of the osmotic delivery device.

2. The method of claim 1, wherein a substantial steady-state delivery of the exenatide at a therapeutic concentration is achieved within a time period of about 7 days after implantation of the osmotic delivery device in the subject.

3. The method of claim 1, wherein the substantial steady-state delivery of the exenatide from the osmotic delivery device is continuous over an administration period of at least about 2 months.

4. The method of claim 1, wherein the method produces a significant decrease in the subject'"'"'s fasting plasma glucose concentration within 7 days after implantation of the osmotic delivery device in the subject, relative to the subject'"'"'s fasting plasma glucose concentration before implantation of the osmotic delivery device.

5. The method of claim 4, wherein the significant decrease in fasting plasma glucose is maintained over the administration period.

6. The method of claim 1, wherein the method produces a decrease in the subject'"'"'s HbA1c % of at least 3% after implantation of the osmotic delivery device in the subject, relative to the subject'"'"'s baseline HbA1c %.

7. The method of claim 1, wherein the decrease in the subject'"'"'s HbA1c % is achieved within about six weeks after implantation of the osmotic delivery device.

8. The method of claim 7, wherein the decrease in the subject'"'"'s HbA1c % is achieved within about two weeks after implantation of the osmotic delivery device.

9. The method of claim 1, wherein the decrease in the subject'"'"'s HbA1c % is maintained over the administration period.

10. The method of claim 1, wherein the osmotic delivery device comprises

an impermeable reservoir comprising interior and exterior surfaces and first and second open ends,

a semi-permeable membrane in sealing relationship with the first open end of the reservoir,

an osmotic engine within the reservoir and adjacent the semi-permeable membrane,

a piston adjacent the osmotic engine, wherein the piston forms a movable seal with the interior surface of the reservoir, the piston divides the reservoir into a first chamber and a second chamber, the first chamber comprising the osmotic engine,

a suspension formulation, wherein the second chamber comprises the suspension formulation and the suspension formulation is flowable and comprises the exenatide, and

a diffusion moderator inserted in the second open end of the reservoir, the diffusion moderator adjacent the suspension formulation.

11. The method of claim 10, wherein the suspension formulation comprises a particle formulation comprising the exenatide and a vehicle formulation.

12. The method of claim 1 or 11, wherein the vehicle formulation comprises a solvent and a polymer.

13. The method of claim 12, wherein the vehicle formulation has a viscosity of between about 10,000 poise and about 20,000 poise at 37°

C.

14. The method of claim 12, wherein the solvent is selected from the group consisting of benzyl benzoate, lauryl lactate, and lauryl alcohol.

15. The method of claim 12, wherein the polymer is a polyvinylpyrrolidone.

16. The method of claim 1, wherein the mcg/day dose of the exenatide is about 20 mcg/day.

17. The method of claim 1, wherein the mcg/day dose of the exenatide is about 40 mcg/day.

18. The method of claim 1, wherein the mcg/day dose of the exenatide is about 60 mcg/day.

19. The method of claim 1, wherein the subject has a baseline HbA1c % of less than or equal to 12.0%.

20. The method of claim 1, wherein the subject is a human.

21. The method of claim 1, wherein the subject has not previously received a drug for treating type 2 diabetes mellitus.

22. The method of claim 1, wherein the subject is further provided one or more other drugs for treating type 2 diabetes mellitus.

23. The method of claim 22, wherein the one or more other drugs is insulin or an anti-diabetic drug selected from the group consisting of a DPP4 inhibitor, a SGLT2 inhibitor, metformin, a sulfonylurea, and a thiazolidinedione (TZD).