In a space where bad news has dominated, diabetes medicine has as its main bright spot the progress of the SGLT-2 drugs, which are set to be the fastest-growing class between now and 2022.
With evidence supporting SGLT-2 efficacy in preventing cardiovascular complications and death, AstraZeneca this morning said it would investigate whether Farxiga can treat chronic kidney disease and heart failure in non-diabetic patients. Meanwhile, Sanofi and Lexicon’s project sotagliflozin reported positive pivotal data in type 1 diabetes, an uncommon case of a non-insulin drug showing signs of working in the autoimmune form of disease.
Just how good is the performance of this class of drugs, which reduce blood glucose by increasing urinary excretion? Boehringer Ingelheim and Lilly’s top seller, Jardiance, has seen its 2020 forecast nearly double, from $1.6bn to $3bn, in the past 12 months.
|SGLT2 and SGLT1/2 outlook|
|Forecast sales ($m)|
|Invokana||canagliflozin||Johnson & Johnson/Mitsubishi Tanabe||1,766||2,456||2,926||3,426|
|Suglat||ipragliflozin L-proline||Astellas Pharma||130||185||225||383|
|Lusefi||luseogliflozin||Taisho Pharmaceutical Holdings||39||60||76||90|
This has been driven by positive data from the Empa-Reg Outcomes trial, which found a statistically significant 14% reduction in cardiovascular events for patients taking Jardiance (EASD – Lilly blooms with full Jardiance outcomes data, September 18, 2015). The FDA is due to decide whether to allow the partners to put the outcomes data on the Jardiance label by September 23.
Empa-Reg Outcomes has pulled along most of the other agents in this class, including Johnson & Johnson and Mitsubishi Tanabe’s Invokana, which has seen its forecasts rise by a third, and Astra and Ono’s Forxiga, up 15%.
Jardiance’s benefit on outcomes centred on sudden cardiovascular death, with the diuretic effect of the agent thought to play a role in relieving the effects of heart failure. Boehringer has already begun a chronic heart failure trial thanks to the findings of Empa-Reg Outcomes.This appears to be the thread Astra intends to follow in initiating the two new phase IIIb trials of Farxiga.
The Farxiga kidney disease trial is more innovative, and it is based on observations that SGLT2s can modulate renal hyperfiltration and other damaging symptoms of the disease. It will not be the first SGLT2 kidney disease trial –Johnson & Johnson has initiated the Credence trial in diabetic nephropathy, for example – but for the first time ever an SGLT2 will be tested in an outcomes trial in non-diabetics with kidney disease, thanks to Astra.
No type 1 error for Sanofi
Lexicon, meanwhile, had been forging a lonely path with its dual-acting SGLT1/2 agent sotagliflozin until it found a willing partner in a Sanofi distressed at the performance of its diabetes pipeline (Sanofi bizdev gets busy and brings in Lexicon, November 6, 2015). This bet has paid off, at least in the clinic, with sotagliflozin showing a statistically significant improvement over placebo in blood glucose levels in type 1 patients on a background of optimised insulin therapy.
Many non-insulin agents have stumbled in type 1, most recently Novo Nordisk’s Victoza. So, with success here, some intriguing commercial possibilities have been raised. Sanofi obviously saw the potential, with three phase III studies well under way before even starting pivotal trials in type 2 disease.
The diabetes space has largely been defined by payer pushback over new products with marginal benefits, something that has affected Sanofi, Lilly and Novo alike. The clinical and commercial performance of SGLT-2s is the one point of relief, and Novo might yet come to regret that it has no interest here.