Metabolic diseases

The category metabolic diseases as defined by the G-BA lists medicinal products for diseases such as diabetes mellitus, certain metabolic enzyme defects such as cystic fibrosis (CF) and hypercholesterolaemia. To date, the G-BA has assessed xx medicinal products in xx resolutions. In total, xx patient populations have been formed. Weighted by patient share in the respective resolution, a major additional benefit has been proved for xx% of the subpopulations, with a considerable additional benefit for XX%. A minor additional benefit has been identified for XX% of the subpopulations, whereas XX% have seen a non-quantifiable additional benefit.
The G-BA has seen no additional benefit proven for XX% of the subpopulations. This corresponds to xx% of the total xx million patients suitable for the assessed medicinal product but for whom no additional benefit was proven in relation to the comparative therapy.

All G-BA resolutions concerning metabolic diseases

Teplizumab (1) Teizeild® Sanofi-Aventis Deutschland GmbH Metabolic diseases Type 1 diabetes mellitus, aged ≥ 8 years 57,000 100% Hint for non-quantifiable additional benefit
Olezarsen (1) Tryngolza® Swedish Orphan Biovitrum GmbH Metabolic diseases Chylomicronemia syndrome 60–130 100% Indication of minor additional benefit Orphan
Diflunisal (1) Attrogy® Purpose Pharma International AB Metabolic diseases Hereditary transthyretin amyloidosis with polyneuropathy (stage 1 or 2) 360 100% additional benefit not proven
Sepiapterin (1) Sephience® PTC Therapeutics International Limited Metabolic diseases Hyperphenylalaninaemia in phenylketonuria 4,700–6,800 100% Hint for non-quantifiable additional benefit Orphan
Vutrisiran (2) Amvuttra® Alnylam Germany GmbH Metabolic diseases Wild-type or hereditary transthyretin amyloidosis with cardiomyopathy 1,760–2,120 100% additional benefit not proven Orphan
Ivacaftor / Tezacaftor / Elexacaftor (17) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis, combination therapy with ivacaftor, ≥ 2 years, non-Class I mutation (a gating mutation and no F508del mutation) 100 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (16) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis, combination therapy with ivacaftor, ≥ 2 years, non-Class I mutation (no F508del mutation and no gating mutation) 375 64% Hint for major additional benefit Orphan (turnover limit)
Tiratricol (1) Emcitate® Rare Thyroid Therapeutics International AB Metabolic diseases Peripheral thyrotoxicosis associated with monocarboxylate transporter 8 deficiency (Allan-Herndon-Dudley syndrome), present from birth 40–110 100% Hint for non-quantifiable additional benefit Orphan
Eplontersen (1) Wainzua® AstraZeneca GmbH Metabolic diseases Hereditary transthyretin amyloidosis with polyneuropathy (stage 1 or 2) 360 100% additional benefit not proven
Acoramidis (1) Beyonttra® Bayer Vital GmbH Metabolic diseases Hereditary transthyretin amyloidosis in adult patients with cardiomyopathy 1,760–2,120 100% additional benefit not proven
Setmelanotid (3) Imcivree® Rhythm Pharmaceuticals Inc. Metabolic diseases Obesity and control of hunger, POMC, PCSK1, LEPR deficiency or Bardet-Biedl syndrome, ≥ 2 to < 6 years of age 24–67 100% Hint for non-quantifiable additional benefit Orphan
Eliglustat (2) Cerdelga® Sanofi-Aventis Deutschland GmbH Metabolic diseases Gaucher disease type 1, ≥ 6 to < 18 years, ≥ 15 kg bw 10–30 100% Hint for non-quantifiable additional benefit Orphan
Insulin icodec (1) Awiqli® Novo Nordisk Pharma GmbH Metabolic diseases Diabetes mellitus type 2 855,000–1,184,000 100% additional benefit not proven
Insulin icodec (2) Awiqli® Novo Nordisk Pharma GmbH Metabolic diseases Diabetes mellitus type 1 161,750 100% additional benefit not proven
Patiromer (2) Veltassa® Fresenius Medical Care Nephrologica Deutschland GmbH Metabolic diseases Hyperkalaemia, ≥ 12 to < 18 years 370–790 100% additional benefit not proven
Pegzilarginase (1) Loargys® Immedica Pharma Germany GmbH Metabolic diseases Hyperargininemia (ARG1-D), ≥ 2 years 50 100% Hint for non-quantifiable additional benefit Orphan
Evinacumab (1) Evkeeza® Ultragenyx Germany GmbH Metabolic diseases Homozygous familial hypercholesterolemia, ≥ 12 years of age 73–80 100% additional benefit not proven
Evinacumab (2) Evkeeza® Ultragenyx Germany GmbH Metabolic diseases Homozygous familial hypercholesterolemia, ≥ 5 to < 12 years of age 5–6 100% additional benefit not proven
Palopegteriparatid (1) Yorvipath® Ascendis Pharma Endocrinology GmbH Metabolic diseases Chronic hypoparathyroidism, parathyroid hormone (PTH) substitution therapy 18,300–20,800 100% additional benefit not proven Orphan
Empagliflozin (6) Jardiance® Boehringer Ingelheim Pharma GmbH Metabolic diseases Diabetes Mellitus Type 2, ≥ 10 years 300–385 100% additional benefit not proven
Alirocumab (3) Praluent® Sanofi-Aventis Deutschland GmbH Metabolic diseases Hypercholesterolaemia, ≥ 8 years to 17 years 958–1,178 100% additional benefit not proven
Ivacaftor / Tezacaftor / Elexacaftor (11) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis, combination treatment with ivacaftor, from 2 to ≤ 5 years of age (heterozygous for F508del and MF mutation) 160 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (12) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis, combination treatment with ivacaftor, 2 to ≤ 5 years (homozygous for F508del mutation) 250 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (13) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis, F508del mutation, heterozygous and gating mutation, ≥ 2 to ≤ 5 years, combination with ivacaftor 13 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (14) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis, F508del mutation, heterozygous and RF mutation, ≥ 2 to ≤ 5 years, combination with ivacaftor 20 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (15) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis, F508del mutation, heterozygous and other or unknown mutation, ≥ 2 to ≤ 5 years, combination with ivacaftor 33 100% additional benefit not proven Orphan (turnover limit)
Patisiran (2) Onpattro® Alnylam Germany GmbH Metabolic diseases Hereditary transthyretin amyloidosis with polyneuropathy (stage 1 or 2) 360 100% Indication of less benefit Orphan (turnover limit)
Tirzepatid (1) Mounjaro® Lilly Deutschland GmbH Metabolic diseases Diabetes mellitus type 2 1,461,000–2,021,000 23% Hint for minor additional benefit
Somapacitan (1) Sogroya® Novo Nordisk Pharma GmbH Metabolic diseases Growth disturbance due to growth hormone deficiency, ≥ 3 years 9,150–11,600 100% Hint for non-quantifiable additional benefit Orphan
Pegunigalsidase alfa (1) Elfabrio® Chiesi GmbH Metabolic diseases Morbus Fabry 60–1,260 100% additional benefit not proven
Lonapegsomatropin (1) Skytrofa® Ascendis Pharma Endocrinology GmbH Metabolic diseases Growth disturbance due to growth hormone deficiency, ≥ 3 to < 18 years. 5,710–6,550 100% Hint for non-quantifiable additional benefit Orphan
Migalastat (3) Galafold® Amicus Therapeutics GmbH Metabolic diseases Fabry disease, ≥ 12 years 20–460 100% additional benefit not proven Orphan (turnover limit)
Cipaglucosidase alfa (1) Pombiliti® Amicus Therapeutics GmbH Metabolic diseases Pompe's disease, combination with miglustat 170–1,760 100% Hint for minor additional benefit
Lumacaftor / Ivacaftor (5) Orkambi® Vertex Pharmaceuticals Metabolic diseases Cystic fibrosis, homozygous F508del mutation in CFTR gene, 1 to < 2 years) 50 100% Hint for non-quantifiable additional benefit
Setmelanotid (2) Imcivree® Rhythm Pharmaceuticals Inc. Metabolic diseases Obesity and control of hunger, Bardet-Biedl syndrome, ≥ 6 years 300–1,100 100% Hint for non-quantifiable additional benefit Orphan
Dulaglutid (3) Trulicity® Lilly Deutschland GmbH Metabolic diseases Diabetes mellitus type 2, ≥ 10 years 640–710 100% additional benefit not proven
Vutrisiran (1) Amvuttra® Alnylam Germany GmbH Metabolic diseases Hereditary transthyretin amyloidosis (hTTA) with polyneuropathy (stage 1 or 2) 360 100% Indication of minor additional benefit Orphan
Olipudase alfa (1) Xenpozyme® Sanofi-Aventis Deutschland GmbH Metabolic diseases Acid sphingomyelinase deficiency (ASMD) type A/B or type B 70–80 100% Hint for non-quantifiable additional benefit Orphan
Burosumab (6) Crysvita® Kyowa Kirin GmbH Metabolic diseases FGF23-related hypophosphatemia in tumour-induced osteomalacia 60–140 100% additional benefit not proven Orphan (turnover limit)
Eladocagene exuparvovec (1) Upstaza® PTC Therapeutics International Limited Metabolic diseases Aromatic L-amino acid decarboxylase (AADC) deficiency, ≥ 18 months 4–30 100% Hint for non-quantifiable additional benefit Orphan
Cerliponase alfa (2) Brineura® BioMarin Deutschland GmbH Metabolic diseases Neuronal ceroid lipofuscinosis (NCL) type 2 40–50 100% Hint for major additional benefit Orphan
Setmelanotid (1) Imcivree® Rhythm Pharmaceuticals Inc. Metabolic diseases Obesity and control of hunger, POMC-, PCSK1- or LEPR-deficient obesity, ≥ 6 years 140–280 100% Hint for non-quantifiable additional benefit Orphan
Somatrogon (1) Ngenla® Pfizer Pharma GmbH Metabolic diseases Growth disturbance due to growth hormone deficiency, ≥ 3 to < 18 years of age 5,710–6,550 100% Hint for non-quantifiable additional benefit Orphan
Ivacaftor / Tezacaftor / Elexacaftor (10) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), F508del mutation, heterozygous and other or unknown mutation, ≥ 6 to ≤ 11 years, combination with ivacaftor 56 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (9) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), F508del mutation, heterozygous and RF mutation, ≥ 6 to ≤ 11 years, combination with ivacaftor 21 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (8) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis, F508del mutation, heterozygous and gating mutation, ≥ 6 to ≤ 11 years, combination with ivacaftor) 28 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (7) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor, 6 to ≤ 11 years (homozygous for F508del mutation) 470 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (6) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor, from 6 to ≤ 11 years (heterozygous for F508del and MF mutation) 233 100% Indication of considerable additional benefit Orphan (turnover limit)
Ivacaftor (27) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), F508del mutation, heterozygous and other or unknown mutation, ≥ 6 to ≤ 11 years, combination with ivacaftor / tezacaftor / elexacaftor 56 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (26) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), F508del mutation, heterozygous and RF mutation, ≥ 6 to ≤ 11 years, combination with ivacaftor / tezacaftor / elexacaftor 21 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (25) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), F508del mutation, heterozygous and gating mutation, ≥ 6 to ≤ 11 years, combination with ivacaftor / tezacaftor / elexacaftor). 28 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (24) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor/tezacaftor/elexacaftor, 6 to ≤ 11 years (homozygous for F508del mutation) 470 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Ivacaftor (23) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor/tezacaftor/elexacaftor, 6 to ≤ 11 years (heterozygous for F508del and MF mutation) 230 100% Indication of considerable additional benefit Orphan (turnover limit)
Calcifediol (1) Rayaldee® Fresenius Medical Care Nephrologica Deutschland GmbH Metabolic diseases Secondary hyperparathyroidism in chronic renal failure 146,700–184,300 100% additional benefit not proven
Burosumab (5) Crysvita® Kyowa Kirin GmbH Metabolic diseases X-linked hypophosphatemia, ≥ 18 years of age 410–810 100% additional benefit not proven Orphan (turnover limit)
Burosumab (4) Crysvita® Kyowa Kirin GmbH Metabolic diseases X-linked hypophosphatemia, ≥ 1 to < 18 years of age 200–550 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Evolocumab (3) Repatha® Amgen GmbH Metabolic diseases Primary hypercholesterolaemia or mixed dyslipidaemia, ≥ 10 to < 18 years of age 768–950 100% additional benefit not proven
Dapagliflozin (7) Forxiga® AstraZeneca GmbH Metabolic diseases Diabetes mellitus Type 2, ≥ 10 years 650–710 100% additional benefit not proven
Ertugliflozin (1) Steglatro® MSD Sharp & Dohme GmbH Metabolic diseases Diabetes mellitus (DM) type 2 1,451,000–2,021,000 100% additional benefit not proven
Icosapent-Ethyl (1) Vazkepa® Amarin Pharmaceuticals Ireland Limited Metabolic diseases Dyslipidemia, pre-treated patients 844,000–878,000 100% additional benefit not proven
Lumacaftor / Ivacaftor (4) Orkambi® Vertex Pharmaceuticals (Europe) Limited Metabolic diseases Cystic fibrosis (CF), homozygous F508del mutation in the CFTR gene, ≥ 2 to ≤ 5 years 290 100% Hint for non-quantifiable additional benefit
Migalastat (2) Galafold® Amicus Therapeutics GmbH Metabolic diseases Fabry disease, 12 to < 16 years 0
1–19
100% Hint for non-quantifiable additional benefit Orphan repealed
Ivacaftor / Tezacaftor / Elexacaftor (5) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor in patients ≥ 12 years (heterozygous for F508del and others or unknown mutation). 310 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (4) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor in patients ≥ 12 years (heterozygous for F508del and RF mutation) 173 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (3) Kaftrio® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor in patients > 12 years (heterozygous for F508del and gating mutation (incl. R117H)). 133 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (22) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor/tezacaftor/elexacaftor in patients ≥ 12 years (heterozygous for F508del and others or unknown mutation) 310 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (21) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor/tezacaftor/elexacaftor in patients ≥ 12 years (heterozygous for F508del and RF mutation) 173 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (20) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor/tezacaftor/elexacaftor in patients ≥ 12 years (heterozygous for F508del and gating mutation (incl. R117H)) 133 100% additional benefit not proven Orphan (turnover limit)
Atidarsagen autotemcel OTL-200 (1) Libmeldy® Orchard Therapeutics GmbH Metabolic diseases Metachromatic leukodystrophy with biallelic mutation in the ARSA gene 2–4 67% Hint for major additional benefit Orphan
Natrium-Zirkonium-Cyclosilikat (1) Lokelma® AstraZeneca GmbH Metabolic diseases Hyperkalemia 77,700–308,500 100% additional benefit not proven
Inclisiran (1) Leqvio® Novartis Pharma GmbH Metabolic diseases Primary hypercholesterolaemia or mixed dyslipidaemia 284,750–410,900 100% additional benefit not proven
Afamelanotid (2) Scenesse® Clinuvel (Europe) Limited Metabolic diseases Erythropoietic protoporphyria 540–1,090 100% Hint for non-quantifiable additional benefit Orphan
Lumasiran (1) Oxlumo® Alnylam Germany GmbH Metabolic diseases Hyperoxaluria 50–880 100% Hint for non-quantifiable additional benefit Orphan
Sebelipase alfa (2) Kanuma® Alexion Pharma Germany GmbH Metabolic diseases Lysosomal acid lipase deficiency 35–70 100% Hint for non-quantifiable additional benefit Orphan
Tezacaftor / Ivacaftor (5) Symkevi® Vertex Pharmaceuticals (Ireland) Limited Metabolic diseases Cystic fibrosis (CF), combination therapy with ivacaftor in patients 6 to < 12 years (heterozygous for F508del and RF mutation) 50 100% additional benefit not proven Orphan (turnover limit)
Tezacaftor / Ivacaftor (4) Symkevi® Vertex Pharmaceuticals (Ireland) Limited Metabolic diseases Cystic fibrosis (CF), combination therapy with ivacaftor in patients 6 to < 12 years (homozygous for F508del) 470 100% additional benefit not proven Orphan (turnover limit)
Tafamidis (4) Vyndaqel® Pfizer Pharma GmbH Metabolic diseases Amyloid cardiomyopathy 1,760–1,810 100% Indication of considerable additional benefit Orphan (turnover limit)
Tafamidis (3) Vyndaqel® Pfizer Pharma GmbH Metabolic diseases Amyloid Neuropathy 230 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (19) Kalydeco® Vertex Pharmaceuticals (Ireland) Limited Metabolic diseases Cystic fibrosis (CF), combination therapy with tezacaftor/ivacaftor in patients 6 to < 12 years (heterozygous for F508del and MF mutation) 50 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (18) Kalydeco® Vertex Pharmaceuticals (Ireland) Limited Metabolic diseases Cystic fibrosis (CF), combination therapy with tezacaftor/ivacaftor in patients 6 to < 12 years (homozygous for F508del mutation) 470 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (17) Kalydeco® Vertex Pharmaceuticals (Ireland) Limited Metabolic diseases Cystic fibrosis (CF), patients from 4 to < 6 months, R117H mutation 1 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Ivacaftor (16) Kalydeco® Vertex Pharmaceuticals (Ireland) Limited Metabolic diseases Cystic fibrosis (CF), patients from 4 to < 6 months, gating mutations 1 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Burosumab (3) Crysvita® Kyowa Kirin GmbH Metabolic diseases X-linked hypophosphatemia (XLH), ≥ 18 years 0
410–810
100% Hint for minor additional benefit Orphan repealed
Bempedoinsäure / Ezetimib (1) Nustendi® Daiichi Sankyo Deutschland GmbH Metabolic diseases Primary hypercholesterolaemia or mixed dyslipidaemia 284,750–286,750 100% additional benefit not proven
Bempedoinsäure (1) Nilemdo® Daiichi Sankyo Deutschland GmbH Metabolic diseases Primary hypercholesterolaemia or mixed dyslipidaemia 284,750–286,750 100% additional benefit not proven
Semaglutid (Rybelsus, Ozempic, 1) Rybelsus, Ozempic® Novo Nordisk Pharma GmbH Metabolic diseases Diabetes mellitus type 2 0
2,107,999–2,108,001
100% additional benefit not proven repealed
Ivacaftor / Tezacaftor / Elexacaftor (2) Kaftrio® Vertex Pharmaceuticals (Ireland) Limited Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor in patients ≥ 12 years (homozygous for F508del mutation) 2,400 100% Indication of major additional benefit Orphan (turnover limit)
Ivacaftor / Tezacaftor / Elexacaftor (1) Kaftrio® Vertex Pharmaceuticals (Ireland) Limited Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor in patients ≥12 years (heterozygous for F508del and MF mutation) 1,000 100% Hint for major additional benefit Orphan (turnover limit)
Ivacaftor (14) Kalydeco® Vertex Pharmaceuticals (Ireland) Limited Metabolic diseases Cystic fibrosis (CF), combination therapy with ivacaftor/tezacaftor/elexacaftor in patients ≥ 12 years (heterozygous for F508del and MF mutation) 1,000 100% Hint for major additional benefit Orphan (turnover limit)
Ivacaftor (15) Kalydeco® Vertex Pharmaceuticals (Ireland) Limited Metabolic diseases Cystic fibrosis (CF), combination therapy with ivacaftor/tezacaftor/elexacaftor in patients ≥ 12 years (homozygous for F508del mutation) 2,400 100% Indication of major additional benefit Orphan (turnover limit)
Osilodrostat (1) Isturisa® Recordati Rare Diseases Germany GmbH Metabolic diseases Endogenous Cushing syndrome 1,130–1,550 100% Hint for non-quantifiable additional benefit Orphan
Ivacaftor (13) Kalydeco® Vertex Pharmaceuticals Metabolic diseases Cystic fibrosis (CF), patients ≥ 6 months to < 18 years 26 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Tezacaftor / Ivacaftor (2) Symkevi® Vertex Pharmaceuticals Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor in patients ≥ 12 years (homozygous for F508del) 2,400 100% additional benefit not proven Orphan (turnover limit)
Tezacaftor / Ivacaftor (3) Symkevi® Vertex Pharmaceuticals Metabolic diseases Cystic fibrosis (CF), combination treatment with ivacaftor in patients ≥ 12 years (heterozygous for F508del) 200–300 100% additional benefit not proven Orphan (turnover limit)
Insulin glargin / Lixisenatid (2) Suliqua® Sanofi-Aventis Deutschland GmbH Metabolic diseases Diabetes mellitus type 2, combination with metformin and with SGLT-2 inhibitors 532,000 100% additional benefit not proven
Givosiran (1) Givlaari® Alnylam Germany GmbH Metabolic diseases Acute hepatic porphyria, ≥ 12 years 1,000–1,700 100% Indication of considerable additional benefit Orphan
Tafamidis (2) Vyndaqel® Pfizer Pharma GmbH Metabolic diseases Amyloid cardiomyopathy 0
1,630–1,730
100% Hint for considerable additional benefit Orphan repealed
Dulaglutid (2) Trulicity® Lilly Deutschland GmbH Metabolic diseases Diabetes mellitus type 2 2,108,000 31% Hint for minor additional benefit
Ivacaftor (12) Kalydeco® Vertex Pharmaceuticals Metabolic diseases Cystic fibrosis (CF), ≥ 6 to < 12 months 2 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Asfotase alfa (2) Strensiq® Alexion Pharma Germany GmbH Metabolic diseases Hypophosphatasia (HPP) 1,074 0.8% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Burosumab (2) Crysvita® Kyowa Kirin GmbH Metabolic diseases X-linked hypophosphatemia (XLH), ≥ 1 to < 18 years 0
200–500
100% Hint for non-quantifiable additional benefit Orphan repealed
Ivacaftor (11) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), 12 ro < 24 months 5 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Ivacaftor (10) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), patients ≥ 18 years with R117H mutation 35–44 100% Hint for minor additional benefit Orphan (turnover limit)
Ivacaftor (9) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), patients from 2 to 5 years 15 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Ivacaftor (8) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), various gating mutations, ≥ 6 years 10–11 100% Hint for non-quantifiable additional benefit Orphan (turnover limit)
Ivacaftor (7) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), heterozygous for F508del, ≥ 12 years, combination with tezacaftor 200–300 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (6) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), homozygous for F508del, ≥ 12 years, combination with tezacaftor 2,400 100% additional benefit not proven Orphan (turnover limit)
Ivacaftor (5) Kalydeco® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), G551D mutation, ≥ 6 years 210 86% Hint for considerable additional benefit Orphan (turnover limit)
Volanesorsen (1) Waylivra® Akcea Therapeutics Germany GmbH Metabolic diseases Chylomicronaemia syndrome 60–120 100% Hint for non-quantifiable additional benefit Orphan
Pegvaliase (1) Palynziq® BioMarin International Limited Metabolic diseases Phenylketonuria 435 100% Hint for non-quantifiable additional benefit Orphan
Dapagliflozin / Metformin (3) Xigduo® AstraZeneca GmbH Metabolic diseases Diabetes mellitus type 2 1,139,000 50% Hint for minor additional benefit
Dapagliflozin (4) Forxiga® AstraZeneca GmbH Metabolic diseases Diabetes mellitus type 2 2,108,000 41% Hint for minor additional benefit
Empagliflozin / Linagliptin (1) Glyxambi® Boehringer Ingelheim Pharma GmbH & Co. KG Metabolic diseases Diabetes mellitus type 2 326,100–341,100 100% additional benefit not proven
Dapagliflozin (3) Forxiga® AstraZeneca GmbH Metabolic diseases Diabetes mellitus type 1 0
19,200
100% Hint for minor additional benefit repealed
Lumacaftor / Ivacaftor (3) Orkambi® Vertex Pharmaceuticals (Europe) Limited Metabolic diseases Cystic fibrosis (CF), homozygous F508del mutation in the CFTR gene, 2 to 5 years 0
280
100% Hint for non-quantifiable additional benefit repealed
Glycerolphenylbutyrat (2) Ravicti® Swedish Orphan Biovitrum GmbH Metabolic diseases Urea cycle disorders (UCD), 0 to < 2 months 10–18 100% non-quantifiable additional benefit Orphan
Tezacaftor / Ivacaftor (1) Symkevi® Vertex Pharmaceuticals (Germany) GmbH Metabolic diseases Cystic fibrosis (CF), F508del mutation, ≥ 12 years 0
2,600–2,700
91% considerable additional benefit Orphan repealed
Insulin degludec (4) Tresiba® Novo Nordisk Pharma GmbH Metabolic diseases Diabetes mellitus type 2 776,100–991,100 100% additional benefit not proven
Alirocumab (2) Praluent® Sanofi-Aventis Deutschland GmbH Metabolic diseases Hypercholesterolemia or mixed dyslipidaemia 271,750 100% additional benefit not proven
Semaglutid (1) Ozempic® Novo Nordisk Pharma GmbH Metabolic diseases Diabetes mellitus type 2 0
1,969,100–2,184,100
37% Hint for minor additional benefit repealed
Patisiran (1) Onpattro® Alnylam Germany GmbH Metabolic diseases Amyloidosis 0
350
100% considerable additional benefit Orphan repealed
Inotersen (1) Tegsedi® Akcea Therapeutics Germany GmbH Metabolic diseases Amyloidosis 350 100% non-quantifiable additional benefit Orphan
Metreleptin (1) Myalepta® Aegerion Pharmaceuticals GmbH Metabolic diseases Lipodystrophy 90–180 100% non-quantifiable additional benefit Orphan
Sitagliptin (3) Januvia, Xelevia® MSD SHARP & DOHME GMBH Metabolic diseases Diabetes mellitus type 2, combination with metformin 781,600 100% Hint for minor additional benefit
Vestronidase alfa (1) Mepsevii® Ultragenyx Germany GmbH Metabolic diseases Mucopolysaccharidosis (MPS VII; Sly syndrome) 2–7 100% non-quantifiable additional benefit Orphan
Velmanase alfa (1) Lamzede® Chiesi GmbH Metabolic diseases Alpha mannosidosis 70–140 100% non-quantifiable additional benefit Orphan
Hydrocortison (1) Alkindi® Diurnal Ltd. Metabolic diseases Adrenal insufficiency, < 18 years 780–1,180 100% additional benefit not proven
Ertugliflozin / Sitagliptin (1) Steglujan® MSD Sharp & Dohme GmbH Metabolic diseases Diabetes mellitus type 2 326,100–341,100 100% additional benefit not proven
Burosumab (1) Crysvita® Kyowa Kirin GmbH Metabolic diseases X-linked hypophosphatemia (XLH), ≥ 1 to < 18 years 0
200–500
100% non-quantifiable additional benefit Orphan repealed
Patiromer (1) Veltassa® Fresenius Medical Care Nephrologica Deutschland GmbH Metabolic diseases Hyperkalemia 61,700 100% additional benefit not proven
Evolocumab (2) Repatha® Amgen GmbH Metabolic diseases Primary hypercholesterolaemia, mixed dyslipidaemia 271,500 100% additional benefit not proven
Glycerolphenylbutyrat (1) Ravicti® Swedish Orphan Biovitrum GmbH Metabolic diseases Urea cycle disorders (UCD), ≥ 2 months 100–250 100% non-quantifiable additional benefit Orphan
Insulin glargin / Lixisenatid (1) Suliqua® Sanofi-Aventis Deutschland GmbH Metabolic diseases Diabetes mellitus type 2 461,400–472,500 100% additional benefit not proven
Lumacaftor / Ivacaftor (2) Orkambi® Vertex Pharmaceuticals (Europe) Limited Metabolic diseases Cystic fibrosis (CF), homozygous F508del mutation in CFTR gene, ≥ 6 years 500 100% Hint for non-quantifiable additional benefit
Dapagliflozin / Metformin (2) Xigduo® AstraZeneca GmbH Metabolic diseases Diabetes mellitus type 2 0
468,700
100% additional benefit not proven repealed
Dapagliflozin (2) Forxiga® AstraZeneca GmbH Metabolic diseases Diabetes mellitus type 2 0
468,700
100% additional benefit not proven repealed
Elosulfase alfa (2) Vimizim® BioMarin Deutschland GmbH Metabolic diseases Mucopolysaccharidosis (type IVA) 20–100 100% minor additional benefit Orphan
Saxagliptin / Metformin (4) Komboglyze® AstraZeneca GmbH Metabolic diseases Diabetes mellitus type 2, combination therapy other than insulin and sulphonylurea 77,400 100% additional benefit not proven
Cerliponase alfa (1) Brineura® BioMarin Deutschland GmbH Metabolic diseases Neuronal ceroid lipofuscinosis type 2 0
20–40
100% non-quantifiable additional benefit Orphan repealed
Etelcalcetid (1) Parsabiv® Amgen GmbH Metabolic diseases Secondary hyperparathyroidism (HPT) 21,896–26,360 100% additional benefit not proven
Sitagliptin / Metformin (2) Janumet, Velmetia® MSD SHARP & DOHME GMBH Metabolic diseases Diabetes mellitus type 2, monotherapy or combination with sulphonylurea or insulin 792,050–810,850 100% additional benefit not proven
Sitagliptin (2) Januvia, Xelevia® MSD SHARP & DOHME GMBH Metabolic diseases Diabetes mellitus type 2, monotherapy or combination with metformin, sulphonylurea or PPARɣ 1,070,800–1,270,800
1,705,400–1,905,400
35% Hint for minor additional benefit repealed subpopulations
Saxagliptin / Metformin (3) Komboglyze® AstraZeneca GmbH Metabolic diseases Diabetes mellitus type 2, monotherapy or combination with insulin 729,650–748,450 100% additional benefit not proven
Saxagliptin (3) Onglyza® AstraZeneca GmbH Metabolic diseases Diabetes mellitus type 2, combination therapy 1,182,900–1,382,900 100% additional benefit not proven
Migalastat (1) Galafold® Amicus Therapeutics GmbH Metabolic diseases Fabry disease 0
20–490
100% non-quantifiable additional benefit Orphan repealed
Empagliflozin / Metformin (1) Synjardy® Boehringer Ingelheim Pharma GmbH & Co. KG Metabolic diseases Diabetes mellitus type 2 615,299–615,301 100% additional benefit not proven
Empagliflozin (2) Jardiance® Boehringer Ingelheim Pharma GmbH & Co. KG Metabolic diseases Diabetes mellitus type 2 1,253,400–1,453,400 42% Hint for considerable additional benefit
Afamelanotid (1) Scenesse® Clinuvel (UK) Limited Metabolic diseases Erythropoietic protoporphyria 0
540–1,090
100% non-quantifiable additional benefit Orphan repealed
Ivacaftor (3) Kalydeco® Vertex Pharmaceuticals (Europe) Limited Metabolic diseases Cystic fibrosis (CF), R117H mutation, 2 to 5 years, > 18 years 0
59
75% minor additional benefit Orphan repealed
Lumacaftor / Ivacaftor (1) Orkambi® Vertex Pharmaceuticals (Europe) Limited Metabolic diseases Cystic fibrosis (CF), > 12 years, homozygous F508del mutation 2,600 100% Indication of considerable additional benefit
Alirocumab (1) Praluent® Sanofi-Aventis Deutschland GmbH Metabolic diseases Hypercholesterolemia or mixed dyslipidaemia 1,500
273,250
100% additional benefit not proven repealed subpopulations
Sebelipase alfa (1) Kanuma® Synageva BioPharma Limited Metabolic diseases Lysosomal acid lipase deficiency 0
31–843
100% non-quantifiable additional benefit Orphan repealed
Asfotase alfa (1) Strensiq® Alexion Europe SAS Metabolic diseases Hypophosphatasia (HPP) 0
1,000
100% non-quantifiable additional benefit Orphan repealed
Evolocumab (1) Repatha® Amgen GmbH Metabolic diseases Primary hypercholesterolaemia, mixed dyslipidaemia 1,810–1,819
273,310–273,319
100% additional benefit not proven repealed subpopulations
Insulin degludec / Liraglutid (2) Xultophy® Novo Nordisk Pharma GmbH Metabolic diseases Diabetes mellitus type 2, combination with oral antidiabetics 78,500–170,000 100% additional benefit not proven
Gaxilose (1) LacTest® VENTER PHARMA S.L. Metabolic diseases Diagnosis of hypolactasia 180,000–230,000 100% additional benefit not proven
Lomitapid (2) Lojuxta® Aegerion Pharmaceuticals GmbH Metabolic diseases Hypercholesterolemia 60–69 100% additional benefit not proven
Insulin degludec / Liraglutid (1) Xultophy® Novo Nordisk Pharma GmbH Metabolic diseases Diabetes mellitus type 2 752,000–903,000 100% additional benefit not proven
Eliglustat (1) Cerdelga® Genzyme GmbH Metabolic diseases Sphingolipidoses (Gaucher disease type 1) 150–500 100% non-quantifiable additional benefit Orphan
Insulin degludec (3) Tresiba® Novo Nordisk Pharma GmbH Metabolic diseases Diabetes mellitus type 1 and type 2, ≥ 1 to < 18 years 20,200 100% additional benefit not proven
Dulaglutid (1) Trulicity® Lilly Deutschland GmbH Metabolic diseases Diabetes mellitus type 2 0
1,705,500–1,905,500
31% Hint for minor additional benefit repealed
Pasireotid (2) Signifor® Novartis Pharma GmbH Metabolic diseases Acromegaly 265–1,133 100% minor additional benefit Orphan
Vildagliptin (2) Galvus, Jalra, Xiliarx® Novartis Pharma GmbH Metabolic diseases Diabetes mellitus type 2 35,900 100% additional benefit not proven
Alipogentiparvovec (1) Glybera® Chiesi GmbH Metabolic diseases Familial lipoprotein lipase deficiency 17–35 100% non-quantifiable additional benefit Orphan
Albiglutid (1) Eperzan® GlaxoSmithKline GmbH & Co. KG Metabolic diseases Diabetes mellitus type 2 1,705,400–1,905,400 35% Indication of minor additional benefit
Ivacaftor (2) Kalydeco® Vertex Pharmaceuticals Limited Metabolic diseases Cystic fibrosis (CF), various mutations, ≥ 6 years 0
10–11
100% minor additional benefit Orphan repealed
Empagliflozin (1) Jardiance® Boehringer Ingelheim Pharma GmbH & Co. KG Metabolic diseases Diabetes mellitus type 2 0
1,253,400–1,453,400
100% additional benefit not proven repealed
Canagliflozin / Metformin (1) Vokanamet® Janssen-Cilag GmbH Metabolic diseases Diabetes mellitus type 2 615,300 100% additional benefit not proven
Insulin degludec (2) Tresiba® Novo Nordisk Pharma GmbH Metabolic diseases Diabetes mellitus type 2, combination with GLP-1 agonists 0
170,100
100% additional benefit not proven repealed
Elosulfase alfa (1) Vimizim® BioMarin Deutschland GmbH Metabolic diseases Mucopolysaccharidosis (type IVA) 0
15–95
100% minor additional benefit Orphan repealed
Cholsäure (1) Orphacol® Laboratoires CTRS Metabolic diseases Bile acid synthesis disorder 10–25 100% non-quantifiable additional benefit Orphan
Insulin degludec (1) Tresiba® Novo Nordisk Pharma GmbH Metabolic diseases Diabetes mellitus type 1 and type 2 161,750
1,095,950
100% additional benefit not proven repealed subpopulations
Canagliflozin (1) Invokana® Janssen-Cilag GmbH Metabolic diseases Diabetes mellitus type 2 1,253,400–1,453,400 100% additional benefit not proven
Dapagliflozin / Metformin (1) Xigduo® Bristol-Myers Squibb GmbH & Co. KGaA/ AstraZeneca GmbH Metabolic diseases Diabetes mellitus type 2 0
615,300
100% additional benefit not proven repealed
Lomitapid (1) Lojuxta® Aegerion Pharmaceuticals GmbH Metabolic diseases Hypercholesterolemia 0
61–71
100% additional benefit not proven repealed
Vildagliptin (1) Galvus, Jalra, Xiliarx® Novartis Pharma GmbH Metabolic diseases Diabetes mellitus type 2 1,669,500–1,869,500
1,705,400–1,905,400
100% additional benefit not proven repealed subpopulations
Vildagliptin / Metformin (1) Eucreas, Icandra, Zomarist® Novartis Pharma GmbH Metabolic diseases Diabetes mellitus type 2 792,050–811,850 100% additional benefit not proven
Sitagliptin / Metformin (1) Janumet, Velmetia® MSD SHARP & DOHME GmbH Metabolic diseases Diabetes mellitus type 2 0
792,050–810,850
78% Hint for minor additional benefit repealed
Sitagliptin (1) Januvia, Xelevia® MSD SHARP & DOHME GmbH Metabolic diseases Diabetes mellitus type 2 0
1,705,400–1,905,400
64% Hint for minor additional benefit repealed
Saxagliptin / Metformin (2) Komboglyze® Bristol-Myers Squibb GmbH & Co. KGaA/ AstraZeneca GmbH Metabolic diseases Diabetes mellitus type 2, combination with sulphonylurea 62,400 100% additional benefit not proven
Saxagliptin (1) Onglyza® Bristol-Myers Squibb GmbH & Co. KGaA / AstraZeneca GmbH Metabolic diseases Diabetes mellitus type 2, combination therapy 0
1,182,900–1,382,900
50% Hint for minor additional benefit repealed
Lixisenatid (1) Lyxumia® Sanofi-Aventis Deutschland GmbH Metabolic diseases Diabetes mellitus type 2 903,000 100% additional benefit not proven
Dapagliflozin (1) Forxiga® Bristol-Myers Squibb GmbH & Co. KGaA/ AstraZeneca GmbH Metabolic diseases Diabetes mellitus type 2 0
896,100
100% additional benefit not proven repealed
Linagliptin (3) Trajenta® Boehringer Ingelheim International GmbH Metabolic diseases Diabetes mellitus type 2 450,000–650,000 100% additional benefit not proven
Saxagliptin / Metformin (1) Komboglyze® Astra Zeneca GmbH & Bristol-Myers Squibb GmbH CO. KG Metabolic diseases Diabetes mellitus type 2 0
729,650–748,450
85% Hint for minor additional benefit repealed
Linagliptin (2) Trajenta® Boehringer Ingelheim International GmbH Metabolic diseases Diabetes mellitus type 2 1,219,500 100% additional benefit not proven
Ivacaftor (1) Kalydeco® Vertex Pharmaceuticals GmbH Metabolic diseases Cystic fibrosis (CF), G551D mutation, ≥ 6 years 0
170
84% considerable additional benefit Orphan repealed
Pasireotid (1) Signifor® Novartis Pharma GmbH Metabolic diseases Pituitary dysfunction 160–360 100% minor additional benefit Orphan
Tafamidis (1) Vyndaqel® Pfizer Pharma GmbH Metabolic diseases Amyloid Neuropathy 0
40–104
100% minor additional benefit Orphan repealed
Linagliptin (1) Trajenta® Boehringer Ingelheim International GmbH Metabolic diseases Diabetes mellitus type 2 0
1,219,500
100% additional benefit not proven repealed
Pitavastatin (1) Livazo® Merckle Recordati GmbH Metabolic diseases Primary hypercholesterolaemia, mixed dyslipidaemia n.d. 100% additional benefit not proven