Sponsor/Drug/ Approval Date	Indication	Primary Evidence	Confirmatory Evidence
Albireo Pharma’s Bylvay (odevixibat) 20 July 2021	Treatment of pruritus in progressive familial intrahepatic cholestasis	Statistically persuasive findings in improvement in pruritus based on observer-reported outcome assessments in Trial A4250-005	Secondary endpoint findings in Trial A4250-005 of reduction in serum bile acid levels, and association between improvement in pruritus scores and reduction in sBA levels for many treated patients; evidence of reduction in sBA levels in a proof-of-concept Phase II trial; nonclinical data supporting mechanistic rationale
Mirum’s Livmarli (maralixibat) 29 September 2021	Treatment of cholestatic pruritus in patients with Alagille syndrome 1 year of age and older	Improvement in pruritus as measured by observer-reported and patient-reported outcome instruments in the Phase II LUM001-304 study	Mechanistic data, including reduction in sBA levels in LUM001-304 and animal model data
Chemocentryx’s Tavneos (avacopan) 7 October 2021	Adjunctive treatment of adult patients with severe active anti-neutrophil cytoplasmic autoantibody-associated vasculitis in combination with standard therapy including glucocorticoids	In Study CL010_168, non-inferiority in remission rate at Week 26 to a high-dose prednisone taper, and superiority in sustained remission rate at Week 52 to a control arm that included patients who received either cyclophosphamide induction on azathioprine maintenance, or rituximab induction with no maintenance	Beneficial effect on rate of relapse, a secondary endpoint, in Study CL010_168; mechanistic data
Enzyvant Therapeutics’ Rethymic (allogeneic processed thymus tissue-agdc) 8 October 2021	Immune constitution in pediatric patients with congenital athymia	Integrated data from subjects with congenital athymia treated in 7 open-label studies and 3 single-patient studies compared to a historical control were deemed to be a single adequate and well-controlled investigation, and demonstrated a mortality benefit and large treatment effect size	Clinically meaningful improvements in infection and additional biochemical and T-cell functional testing data to indicate immune reconstitution; biologic plausibility
Genzyme’s Xenpozyme (olipudase alfa-rpcp) 31 August 2022	Treatment of non–central nervous system manifestations of acid sphingomyelinase deficiency in adult and pediatric patients.	Diffusion capacity for carbon monoxide primary endpoint and spleen volume showed a statistically significant advantage for adults over placebo in the ASCEND (DFI12712) trial	Well-established etiology of disease; mechanism of action of therapy; and pharmacodynamic biomarker data from clinical trials, including ASCEND
bluebird bio’s Skysona (elivaldogene autotemcel) 16 September 2022	To slow the progression of neurologic dysfunction in boys 4-17 years of age with early, active cerebral adrenoleukodystrophy	Pooled data from 2 single-arm, open-label studies compared to external controls were considered a single adequate and well-controlled investigation; accelerated approval based primarily on a Kaplan-Meier time-to-event analysis in a symptomatic subset of Skysona-treated subjects and similar untreated controls, with Skysona slowing the progression of neurologic dysfunction assessed by major functional disabilities or death	Trends toward delayed symptom onset in a small number (n=5) of Skysona-treated subjects based on disease modeling; imaging and pharmacodynamic markers
Source: FDA review documents

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