After its protracted development, the positive result in the LixiLan-O phase III study will no doubt be welcomed by Sanofi as much as the lixisenatide component’s originator, Zealand Pharma. But even assuming that LixiLan now enjoys a smooth path to market – not yet a given – it is unlikely that this will prevent the French group losing share in the global diabetes category.
Sanofi’s diabetes franchise is centred on Lantus, the leading basal insulin, but this is likely to see competition from biosimilar versions next year and could lose as much as $3bn of sales by 2020, EvaluatePharma consensus data suggest (see tables below). Sanofi’s newly launched basal insulin, Toujeo, should make up around half of this loss, but Lyxumia, the GLP-1 agonist monotherapy, and LixiLan, the combination with Lantus, only bring in $371m and $493m by 2020 respectively.
Thus Sanofi’s combined insulin/GLP-1 franchise is thought likely to stagnate in sales terms at around $8bn a year over the next five years, while competing products from Novo Nordisk and Lilly are expected to enjoy double-digit growth.
Sanofi will see its share of these two segments decline from just under 35% currently to 24% by 2020, while both Novo and Lilly are expected to see large share gains over this period. And growth at the two competitors comes from both insulins and GLP-1 agonists.
|Combined GLP-1 agonist/insulin sales|
|Sales ($m)||Share of total|
At one point around the turn of the decade, it had seemed that lixisenatide would drive growth in Sanofi’s diabetes franchise. However, the product’s long history of delays and the switch in commercial focus to the combination – which then itself saw various setbacks – means that it is likely to come to market a little too late.
Xultophy, Novo Nordisk’s own GLP-1/insulin combo, which has perhaps a two-year headstart over LixiLan outside the US, is expected to see sales of $1.1bn by 2020. The two products, however, are on a similar timeline in the US.
Nevertheless, Sanofi will be pleased that the 1,170-patient LixiLan-O trial met its primary endpoint. The trial showed a statistically superior reduction in HbA1c compared with both of the drug’s components given as single agents, although specific data were not disclosed. LixiLan-O enrolled type 2 diabetics who were insufficiently controlled on metformin, either alone or with a second oral anti-diabetic, randomised for 30 weeks.
The remaining hurdles for the product are now the outcome of the second phase III, LixiLan-L, which should read out shortly, and the need to gain US approval for the single agent, Lyxumia. The 700-patient LixiLan-L study compares LixiLan with Lantus in type 2 diabetics, with or without metformin.
Sanofi is believed to have filed Lyxumia in the US earlier this month, and will presumably confirm this once the file has been accepted for review. The US filing was delayed by the need to include results from the Elixa cardiovascular outcomes study. This 6,068-patient trial rendered a positive result, showing the drug to be non-inferior – although not superior – to placebo (GLP-1s' first outcomes study unlikely to lift Lyxumia, March 19, 2015).
Assuming a positive result in LixiLan-L, Sanofi will be on course to file next year and might see approval in the first half of 2017. It will still have to steer a difficult commercial path with biosimilar competition to Lantus on one hand and a desire drive Toujeo sales on the other, to say nothing of the actions of other competitors.
|Forecast diabetes drug sales for insulin, GLP-1 and combinations ($m)|
|NovoRapid||insulin aspart||Novo Nordisk||3,303||4,434||6.1%|
|Levemir||insulin detemir||Novo Nordisk||2,841||3,055||1.5%|
|Humalog||insulin lispro||Eli Lilly||2,854||2,994||1.0%|
|NovoMix 30||insulin aspart||Novo Nordisk||1,635||2,204||6.2%|
|Tresiba||insulin degludec||Novo Nordisk||197||1,664||53.3%|
|Abasria/Basaglar||insulin glargine||Eli Lilly||33||631||80.6%|
|Peglispro||insulin peglispro||Eli Lilly||0||612||N/A|
|Ryzodeg||insulin aspart/ degludec||Novo Nordisk||53||463||54.1%|
|Insulin analogues||insulin||Novo Nordisk||399||440||2.0%|
|Xultophy||insulin degludec; liraglutide||Novo Nordisk||35||1,107||99.8%|
|LixiLan||insulin glargine; lixisenatide||Sanofi||0||493||N/A|