Disease characteristics and tissue frataxin concentrations in adults with Friedreich's ataxia participating in nomlabofusp interventional studies
Clinical Genetics and Therapeutics
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Primary Categories:
- Clinical-Adult
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Secondary Categories:
- Clinical-Adult & Pediatric
Introduction:
During the clinical development of therapies targeting rare genetic diseases, it is important to include study participants whose characteristics represent a broad range of the affected population in order to generalize study findings across the spectrum of patients living with the disease. Friedreich’s ataxia (FRDA) is a rare autosomal recessive disease in which guanine adenine adenine (GAA) repeat expansions result in partial gene silencing and decreased production of the protein frataxin (FXN). Early age of onset and lower tissue FXN concentrations are associated with more rapid disease progression. Nomlabofusp is being developed as a therapy to increase tissue FXN concentrations in patients with FRDA. Inclusion criteria for Phase 1 and Phase 2 studies were set as broad as possible in order to enroll adult patients over a range of disease characteristics such that the population of patients participating in the nomlabofusp clinical program is representative of the general population of patients with FRDA.
Methods:
Disease characteristics (e.g. age at onset, GAA repeat length) of adults with FRDA participating in Phase 1 and 2 nomlabofusp interventional studies were summarized and evaluated relative to baseline buccal and skin cell frataxin concentrations.
Results:
Sixty-one subjects participated in at least one study; 18 participated in more than one study. Mean age was 31.9 years (range 19- 69). Mean age of onset was 15.9 years (range 5- 60). Mean (range) shorter and longer GAA repeat lengths were 555.8 (99- 1000) and 890.2 (265- 1300). Mean baseline modified Friedreich’s ataxia Rating scale neurologic score was 49.5 (13.2- 74.5). Mean (range) baseline buccal and skin cell frataxin concentrations were 1.90 (0.70- 4.95) and 3.25 (1.40- 8.10) pcg/mcg, respectively. There is a relationship between FXN concentrations and age of onset and GAA repeat length. There is also a relationship between skin and buccal cell frataxin concentrations.
Conclusion:
Tissue frataxin concentration data from these studies are consistent with prior studies demonstrating that lower frataxin concentrations are associated with earlier onset of disease. The range of characteristics observed in the population of patients with FRDA participating in the nomlabofusp interventional studies is representative of the general FRDA adult population. Buccal and skin cell frataxin levels correlate with each other.
During the clinical development of therapies targeting rare genetic diseases, it is important to include study participants whose characteristics represent a broad range of the affected population in order to generalize study findings across the spectrum of patients living with the disease. Friedreich’s ataxia (FRDA) is a rare autosomal recessive disease in which guanine adenine adenine (GAA) repeat expansions result in partial gene silencing and decreased production of the protein frataxin (FXN). Early age of onset and lower tissue FXN concentrations are associated with more rapid disease progression. Nomlabofusp is being developed as a therapy to increase tissue FXN concentrations in patients with FRDA. Inclusion criteria for Phase 1 and Phase 2 studies were set as broad as possible in order to enroll adult patients over a range of disease characteristics such that the population of patients participating in the nomlabofusp clinical program is representative of the general population of patients with FRDA.
Methods:
Disease characteristics (e.g. age at onset, GAA repeat length) of adults with FRDA participating in Phase 1 and 2 nomlabofusp interventional studies were summarized and evaluated relative to baseline buccal and skin cell frataxin concentrations.
Results:
Sixty-one subjects participated in at least one study; 18 participated in more than one study. Mean age was 31.9 years (range 19- 69). Mean age of onset was 15.9 years (range 5- 60). Mean (range) shorter and longer GAA repeat lengths were 555.8 (99- 1000) and 890.2 (265- 1300). Mean baseline modified Friedreich’s ataxia Rating scale neurologic score was 49.5 (13.2- 74.5). Mean (range) baseline buccal and skin cell frataxin concentrations were 1.90 (0.70- 4.95) and 3.25 (1.40- 8.10) pcg/mcg, respectively. There is a relationship between FXN concentrations and age of onset and GAA repeat length. There is also a relationship between skin and buccal cell frataxin concentrations.
Conclusion:
Tissue frataxin concentration data from these studies are consistent with prior studies demonstrating that lower frataxin concentrations are associated with earlier onset of disease. The range of characteristics observed in the population of patients with FRDA participating in the nomlabofusp interventional studies is representative of the general FRDA adult population. Buccal and skin cell frataxin levels correlate with each other.