Expanded Access to 0.5 mg eRapa for Familial Adenomatous Polyposis

Expanded Access Program for 0.5 mg eRapa in Familial Adenomatous Polyposis

This expanded access program provides 0.5 mg eRapa (encapsulated rapamycin) to patients with familial adenomatous polyposis (FAP) who have no satisfactory alternative treatment options and are not eligible to participate in a clinical trial. The objective is to provide access to eRapa based on the treating physician's assessment that the potential benefits outweigh the potential risks, with appropriate clinical monitoring for safety and tolerability.

amilial adenomatous polyposis (FAP) is an inherited cancer predisposition syndrome characterized by the development of numerous colorectal adenomas and an increased risk of colorectal and other gastrointestinal malignancies. Although prophylactic surgery substantially reduces the risk of colorectal cancer, patients frequently continue to develop adenomas in the remaining gastrointestinal tract, and effective medical therapies to reduce polyp burden are limited.

Rapamycin inhibits the mammalian target of rapamycin (mTOR) signaling pathway, which regulates cell growth, proliferation, and survival. Dysregulation of mTOR signaling has been implicated in intestinal tumorigenesis associated with FAP, providing a biological rationale for mTOR inhibition as a therapeutic approach.

This expanded access program is intended to provide treatment with 0.5 mg eRapa (encapsulated rapamycin) for eligible patients with FAP when participation in a clinical trial is not feasible or available and no comparable or satisfactory therapeutic alternatives exist. Treatment decisions, dosing, duration of therapy, and clinical monitoring will be determined by the treating physician in accordance with the program inclusion and exclusion policy. Patients will undergo appropriate assessments to monitor safety, tolerability, and clinical status throughout treatment.

Inclusion Criteria:

1. Patient is post pubertal and reached full adult height
2. Patient has FAP confirmed by APC genotype mutation tesing or a history of FAP in one of the parents. Genetic mosaics or Attenuated (as well as classical) FAP may participate
3. Patient has significant colorectal and/or duodenal FAP disease burden.

Exclusion Criteria:

1. Patient has existing carcinoma or high-grade dysplasia in the GI tract and/or requires imminent definitive surgical intervention (either partial or complete colectomy or duodenectomy).
2. Patient with an acquired or congenital immunodeficiency, active and clinically significant tuberculosis, bacterial, fungal, or viral infections, including HIV.
3. Patient has clinically significant elevations of hepatic enzymes or bilirubin, or other evidence of active hepatitis.
4. Patient has clinically significant impairment of renal function.
5. Patient has a history or evidence of clinically significant hyperlipoproteinemia or hypertriglyceridemia.
6. Patient has active or recurrent bouts of pancreatitis, or clinically significant elevations of lipase or amylase.
7. Patient is taking medications that are considered strong inducers or inhibitors of cytochrome P450 (CYP) 3A4/5 or strong inducers or inhibitors of P-glycoprotein 1 (P-gp1) that cannot be discontinued at least 1 week prior to first dose of treatment intervention and for the duration of the treatment.
8. Patients with known hypersensitivity to rapamycin (sirolimus) or any of the excipients in eRapa.
9. Sexually active patients who are unwilling to use a highly effective contraceptive method and to refrain from donating gametes (sperm or oocytes) throughout the time they are receiving eRAPA and for 12 weeks beyond that time, and to refrain from breast-feeding their children while on treatment.
10. Patients who are pregnant or who are trying to become pregnant while taking eRapa.
11. Patients unwilling or unable to undergo continued endoscopic surveillance in accordance with standards of care while taking eRapa.
12. Patient has Mutations in the MUTYH gene.