Rare disease: Smith-Kingsmore syndrome (SKS)

  There are no FDA-approved drugs for SKS

SKS is a rare, neurodevelopmental genetic disorder, which impacts the digestive, endocrine, metabolic and nervous systems.

Sirolimus is currently being used off label for patients with SKS to treat intractable seizures.

Rare disease: Pachyonychia Congenita (PC)

  There are no FDA-approved drugs for PC.

PC is an ultra-rare, chronic, genetic autosomal dominant skin disorder, which causes lifelong limited mobility and severe pain.

Palvella therapeutics is currently conducting a Phase III clinical trial to evaluate QTORIN™, a 3.9% topical sirolimus.” this trial is being conducted in partnership with PC Project, utilizing their patient registry of genetically confirmed patients.

Palvella has been awarded both FDA Orphan Drug and Fast Track designation.

Rare disease: Lymphangioleiomyomatosis (LAM)

  Sirolimus was FDA approved for LAM in 2015.

LAM is a rare lung disease that almost exclusively affects women; it's characterized by an abnormal growth of smooth muscle cells, especially in the lungs, lymphatic system and kidneys.

Unregulated growth of these cells can lead to loss of lung function, accumulation of lymph rich-fluid in the chest and abdomen and growth of tumors in the kidneys.

Rare disease: Hereditary Hemorrhagic Telangiectasia (HHT)

  There are no FDA-approved drugs for HHT

HHT is a genetic disorder that causes malformed blood vessels and can affect multiple organs of the body. The disorder is also sometimes referred to as Osler-Weber-Rendu (OWR).

Currently, sirolimus in a Phase II clinical trial for patients with HHT that are experiencing moderate or severe epistaxis

Rare disease: Complex Lymphatic Anomalies

  There are no FDA-approved drugs for CLAs.

CLAs are a group of rare diseases that are characterized by abnormal growth of lymphatic vessels that may involve multiple organ systems, including lung, spleen, soft tissue and bones

Sirolimus has shown efficacy in phase II clinical trials and is being used off label; It is currently one of the frontline agents for patients with complex lymphatic anomalies.

Rare disease: RUNX1 familial platelet disorder

  There are no FDA-approved drugs for RUNX1-FPD.

RUNX1 FPD is a hereditary blood disorder causing bleeding, bruising, inflammatory conditions and a 40-50% lifetime risk of developing blood cancer

Preclinical data identified sirolimus as promising; currently developing a clinical trial.

Rare disease: Castleman Disease

  CD has one FDA-approved drug, siltuximab (Sylvant), which is effective for about 30-50% of CD patients.

CD is a group of rare disorders that involve enlarged lymph nodes and a broad range of inflammatory symptoms and laboratory abnormalities. In CD, the cells of the immune system become hyperactivated, overproduce cytokines and other inflammatory compounds, and fail to return to a surveillance mode.

Dr. Fajgenbaum discovered the potential for treating CD with Sirolimus in 2014.

Sirolimus is currently being used off-label for patients with iMCD and UCD, and is being studied in a Phase II clinical trial .

Rare disease: Idiopathic Inflammatory Myopathies (IIM)

  There are limited FDA-approved therapies for some forms of myositis outside corticosteroids and IV-IG. However, no treatment is available for IBM.

IIM, commonly referred to as myositis, are a group of rare, sporadic, systemic autoimmune diseases including dermatomyositis, inclusion body myositis (IBM), and necrotizing myositis. While myositis is classified as a muscle disease, it can also affect the skin, lung, heart, and joints and can be associated with cancer.

A randomised, double-blind, placebo-controlled, proof-of-concept, Phase 2b clinical trial was completed in 2020, which showed no evidence of sirolimus efficacy in IBM based on the primary end-point; however, the researchers found enough evidence of benefit in certain secondary outcomes to suggest conducting a phase 3 trial, which is now being financed by an Australian government grant and currently in the recruiting phase

Some patients are using sirolimus off-label, but it is not currently integrated into treatment guidelines.

Rare disease: Fibro-adipose vascular anomaly (FAVA)

  In April, 2022, the FDA granted approval on an accelerated basis for Novartis's Vijoice (alpelisib) to treat FAVA and other conditions under the PROS umbrella, with studies continuing to potentially lead to full approval.

FAVA is a rare vascular anomaly occurring when the body’s own tissue infiltrates a muscle, creating a tumor-like mass typically found in one or more limbs.

Sirolimus is currently being used off-label.