Table 1.
Individual data for the 11 patients
| Parameter | Patient | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | |
| Sex | Female | Male | Male | Male | Female | Male | Female | Male | Male | Female | Male |
| Age, years | 13 | 12 | 16 | 7 | 11 | 16 | 4 | 14 | 15 | 11 | 9 |
| Genetic variant |
LDLR c.313 + 5 G > A |
LDLR c.682G > T | LDLR c.119_1207del | LDLR c.666C > A, c.1646C > A | c.-187-? 940 + ? Dup | LDLR c.131G > A, c.2043C > A | LDLR c.2043C > A | LDLR c.1846-? 2311 + ?del, c.1895A > T |
LDLR c.313 + 1 G > A, del exon 1–6 |
LDLR c.1731G > T | LDLR c.1731G > T |
| LDL-C at diagnosis, mg/dL | 799 | 672 | 981 | 1008 | 1009 | 901 | 739 | 474 | 982 | 1002 | 824 |
| LLT prior to lomitapide | Statins, ezetimibe, LA | Statins, ezetimibe, LA | Statins, ezetimibe, LA, EV | Statins, ezetimibe, bile acid sequestrant | Statins, ezetimibe | Statins, ezetimibe, LA, Ev | Statins, ezetimibe | Statins, ezetimibe | Statins, ezetimibe, LA, Ev | Statins, ezetimibe, bile acid sequestrant | Statins, ezetimibe, bile acid sequestrant |
| Duration of therapy prior to lomitapide, years | 11 | 2 | 14 | 3 | 8 | 6 | < 1 | 6 | 11 | 8 | 8 |
| LDL-C prior to lomitapide, mg/dL | 299 | 326 | 187 | 833 | 443 | 274 | 649 | 223 | 81 | 630 | 705 |
| LDL-C at nadir, mg/dL | 56 | 98 | 73 | 360 | 231 | 23 | 236 | 75 | 62 | 441 | 460 |
| Concomitant LLT |
Atv 40mg Ez 10mG LA Q2W |
Ro 20mg Ez 10mg LA Q15D |
Ro 20mg Ez 10mg Ev 420mg QW Co 3250mg LA Q1W |
Ro 20mg Ez 10mg Co 625mg |
Atv 10mg Ez 10mg |
Ro 20mg Ez 10mg LA Q2W |
Atv 10mg Ez 5mg |
Ro 30mg Ez 10mg |
Atv 40mg Ez 10mg LA 2xW |
Atv 40mg Ez 10mg Cholestyramine 4g |
Atv 40mg Ez 10mg Cholestyramine 4g |
| Maximal reduction with lomitapide, % | 81 | 70 | 61 | 57 | 48 | 92 | 64 | 66 | 24 | 27 | 34 |
| Maximum dose of lomitapide, mg/day | 20 | 40 | 60 | 30 | 20** | 30 | 15 | 15*** | 15 | 20 | 20 |
| Length of lomitapide exposure, months | 17 | 15 | 20 | 15 | 48 | 15 | 12 | 22 | 18 | 19 | 19 |
| Change in concomitant LLT |
Ev stopped§ LA stopped |
Ev stopped§ LA reduced to Q4W |
Ev stopped§ Ro stopped LA reduced to Q2W |
None |
Atv 40mg† Atv 60mg† |
Ev stopped§ Ro 30mg Ro 40mg**** LA stopped |
None |
Ez stopped§ LA stopped |
LA reduced 75% Ev stopped§ |
None | None |
| Liver Status | Liver enzymes normal | Liver enzymes normal | Elevated liver enzymes resolved after Ro stopped | Liver enzymes normal | Liver enzymes normal | Minimal ALT increase resolved without intervention | Liver enzymes normal | ALT increases managed with lomitapide dose reduction | Liver enzymes and liver imaging normal | Liver enzymes normal | Liver enzymes normal |
| Adverse events¶ | Nausea, vomiting, Diarrhoea, frequent bowel movements | Diarrhoea, vomiting | Flatulence, hypertransaminasaemia | None | Diarrhoea | Gastrointestinal pain, Hhpertransaminasaemia | Diarrhoea | Hypertransaminasaemia | None | None | None |
AE, adverse events; ALT, alanine aminotransferase; At, atorvastatin; Co, colesevalem; Ev, evolocumab (all Ev stopped prior to lomitapide); Ez, ezetimibe; GI, gastrointestinal; LA lipoprotein apheresis; LDL-C, low-density lipoprotein cholesterol; LLT, lipid-lowering therapies.
All oral drug doses are daily
**patient briefly received 30mg/day before back-titration to 20mg/day
***patient briefly received 20mg/day before back-titration to 15mg/day
****subsequent, post-hoc reduction to Ro 35mg
†atorvastatin dose changes – Atv dose increased to 60mg near end of observation period
§patient had also received evolocumab (no response), which had been stopped before commencement on lomitapide
¶MedDRA preferred term