Table 1.
Patient characteristics, drug product information, and reported outcomes after Lyfgenia and Casgevy
| Lyfgenia | Casgevy | |
|---|---|---|
| Patient characteristics | ||
| Patients treated, n (%) | 36 (100) | 44 (100) |
| Patients evaluable for efficacy outcomes, n (%) | 32 (89) | 31 (70) |
| β-Globin genotype, n (%) | ||
| βSβS | 36 (100) | 40 (91) |
| βSβ0 | 0 (0) | 3 (7) |
| βSβ+ | 0 (0) | 1 (2) |
| 2 α-globin gene deletion, n (%) | 2 (6) | 2 (5) |
| Age in years, median (min, max) | 24 (12, 38) | 20 (12, 34) |
| Age ≥12 years and ≤17 years, n (%) | 8 (22) | 12 (27) |
| History of stroke,a n (%) | 5 (14%) | NR |
| No. of mobilization cycles, n (min, max) | 2 (1,4) | 2 (1,6) |
| Time to neutrophil engraftment,b median days (min, max) | 20 (12, 35) | 27 (15, 40) |
| Time to platelet engraftment,c median days (min, max) | 35 (19, 136) | 35 (23, 126) |
| Drug product characteristics | ||
| VCN, copies/diploid genome, median (min, max) | 4.0 (2.3, 6.6) | N/A |
| Percentage of allelic editing in bone marrow, mean (SD) | N/A | 88.5 (4.6)d |
| Outcomes | ||
| Severe VOE complete resolution, n/N (%) [CI] | 30/32 (94%) [79, 99]e | 29/31 (94%) [78,100]f |
| Globin response,g n/N (%) | 31/36 (86) | NR |
| Proportion of total hemoglobin comprised by HbF (%), median (min, max) | N/A | 42.2 (33.3, 49.1)h |
| Total hemoglobin gm/dL, median (min, max) | 11.8 (8.4–15.0) | 13.0 (10.5, 17.3)i |
| Duration of follow-up in months, median (min, max) | 38 (12, 61) | 19 (0.8, 48) |
| Notes | ||
| Lyfgenia | 4/32 patients who achieved VOE-CRe experienced VOEs after primary efficacy endpoint; 17/35 (49%) were prescribed opiates for sickle-related and non-sickle-related pain up to 24 months post-infusion; all 5 individuals with prior stroke remain transfusion independent without recurrent stroke at 44–60 months | |
| Casgevy | 6 (10%) patients were unable to receive Casgevy therapy due to not achieving the minimum dose after mobilization; one VF12f responder, after initially achieving a VF12 response, experienced an acute pain episode meeting the definition of a severe VOC at month 22.8 requiring a 5 day hospitalization; this patient was reported to have a parvovirus B19 infection at the time | |
CI, confidence interval; CR, complete response; HbF, fetal hemoglobin; VCN, vector copy number; VF, vaso-occlusive free; VOC, vaso-occlusive crisis; VOE, vaso-occlusive event; NR, not reported.
Patients with a history of stroke were included in early inclusion criteria.
Defined as the first day of 3 consecutive measurement of absolute neutrophil count ≥500 cells/μL on 3 different days.
Defined as the first day of 3 consecutive measurement of unsupported (no platelet transfusion in last 7 days) platelet count ≥50,000/μL on 3 different days.
n = 16 at month 24.
Defined as elimination of severe VOE requiring hospital admission or multiple visits to an emergency department and receiving intravenous medications or priapism requiring any level of medical attention between 6 and 18 months post-infusion with Lyfgenia.
Defined as no protocol-defined severe VOCs for at least 12 months within the first 24 months after Casgevy infusion.
Defined as meeting the following criteria for a continuous period of ≥6 months: weighted average HbAT87Q ≥30% non-transfused total Hb and weighted average increase in non-transfused total Hb of ≥3 g/dL vs. baseline total Hb or weighted average non-transfused total Hb of ≥10 g/dL.
Proportion of total Hb comprised by HbF (%) at month 24, n = 17.
n = 17 at month 24.