ABOUT

AMYLOIDOSIS

SYSTEMIC AMYLOIDOSIS

(Non-CNS)

Amyloid diseases are a diverse group of disorders, characterized by the deposition of protein fibrils in vital organs and tissues. There are approximately 30 different types of amyloidosis, each resulting from the misfolding and aggregation of a specific protein They are severely debilitating, progressive, and often fatal.

5 most common types of systemic amyloidosis (Non-CNS):

  1. Wild-type transthyretin amyloidosis (wtATTR)​

    • 13% of HFpEF patients may have wtATTR

    • >300K patients in US and EU15

    • Mainly manifests in heart and ligaments and tendons

    • Median Survival: 3-5 years

  2. Hereditary transthyretin amyloidosis (hATTR)

    • 3-4% of African Americans carry the V122I (V142I) mutation

    • >75K patients in US and EU15

    • Manifests in heart, nerves, GI and kidneys

    • median survival: 10 years; 3-5 years with cardiac involvement

  3. Light Chain amyloidosis (AL)

    • 15-20% of MM patients have co-existing AL​

    • >40K patients in US and EU15

    • Manifests in every organ: >70% have cardiac and or kidney

    • Median Survival: 4 years; 2-3 years with cardiac involvement

  4. Leukocyte Chemotactic Factor 2 amyloidosis (ALECT2)

    • LECT2 deposits found in~3% of Hispanic descendants 

    • Unknown prevalence

    • Manifests mainly in kidney and liver

  5. Amyloid A amyloidosis (AA)

    • ~10K patients in US and EU15: common in developing nations

    • Manifests mainly in kidneys

  6. Other 25 Systemic Amyloid Diseases (e.g. apolipoprotein AI (AApoAI), gelsolin (AGel), lysozyme (ALys))

    • Ultra-rare: <10K in US and EU15 in aggregate​

    • Manifests in various organs, with about half affecting kidneys

View a list of all 30 non-CNS amyloid diseases here.

AMYLOID HYPOTHESIS:

PROVEN in Systemic Amyloidosis

Amyloid is a validated target in systemic amyloidosis. Therapies recently approved in ATTR amyloidosis have proven that reducing or stabilizing the pre-cursor protein leads to improves clinical outcomes. In AL amyloidosis, off-label agents including chemotherapy and Autologous Stem Cell Transplant, which both reduce the precursor protein have also been shown to improve clinical outcomes. These therapies work by reducing production of new amyloid.

CURRENT

TREATMENTS

29 out of 30 systemic amyloid diseases have no approved treatment.

ATTR: 3 treatments have regulatory approval and are marketed.

  • Gene silencing drugs inotersen and patisiran approved for hATTR with polyneuropathy​.

  • Tetramer stabilizer drug tafamidis approved for ATTR-CM (both hereditary and wild-type).

AL: No approved treatments

  • ASCT and chemotherapy drugs such as bortezomib and lenalidomide ​are off-label standard of care​.

UNMET

NEEDS

There is a significant need for a diagnostic: Most patients go undiagnosed; of those who are diagnosed, most are diagnosed late.

  • Early diagnosis has been shown to improve patient outcomes​.

  • Currently, patients receive a significant number of tests prior to a diagnosis.

  • An invasive biopsy followed by congo red staining and mass spectrometry is still required for most patients.

  • Approved treatments are needed for 29 out of 30 diseases.

  • ATTR treatments do not directly address resident amyloid, especially in the heart where amyloid load is substantial.

  • AL treatments (off-label) do not directly address resident amyloid.

  • Despite treatments for these 2 diseases, the median survival and QoL for patients is still poor.

  • There is a significant need for therapies that address the amyloid causing dysfunction in tissues and organs.

DELAYS IN DIAGNOSIS

There is a substantial unmet need to improve the diagnosis of amyloidosis in patients. The majority of systemic amyloidosis patients see more than 4 specialists and take more than 18 months to get an accurate diagnosis, with 25% of patients taking more than 5 years to get a correct diagnosis. Unfortunately a significant number of patients expire without a diagnosis.

 

Currently, there are a number of diagnostic procedures required to appropriately detect systemic amyloid diseases, with clear challenges in getting an early and accurate diagnosis. 

Responses from a survey of >700 cardiac amyloid patients show numerous physician consultations, and diagnostic procedures before diagnosis.

Amyloidosis Research Consortium Cardiac Amyloidosis Survey: Results from Patients with AL and ATTR Amyloidosis and Their Caregivers

Isabelle Lousada1, Mathew S. Maurer2, Melissa Warner1, Spencer Guthrie3, Kristen Hsu1, Martha Grogan4 1Amyloidosis Research Consortium, Boston, MA, USA; 2Columbia University, New York, NY, USA; 3Aurora Bio, USA;4Mayo Clinic, Rochester, MN, USA

 

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