Partners Boehringer Ingelheim and Eli Lilly have announced positive top-line results from the Phase III clinical trials of their SGLT-2 inhibitor empagliflozin in the treatment of type-2 diabetes, while Boehringer has decided to pull out of the project to develop a new basal insulin analogue.
IHS Global Insight perspective | |
Significance | Boehringer Ingelheim and Eli Lilly have announced positive top-line results for Phase III clinical trials of their SGLT-2 inhibitor empagliflozin in type-2 diabetes; Boehringer has also announced its withdrawal from the development of a basal insulin analogue with Lilly, intending to pursue this project on its own. |
Implications | With competitors already at more advanced stages in placing SGLT-2 inhibitors on the market, Boehringer and Lilly will be hoping for a smooth late clinical trial stage in order to get ahead with the administrative process. |
Outlook | Boehringer’s choice to discontinue its involvement in the development of the basal insulin analogue, which is set to enter Phase III trials, at the same time as its affirmation of its commitment to empagliflozin and another oral type-2 diabetes product, Trajenta, is interesting from the strategic side, and suggests that apart from the insulin glargine product being developed with Lilly, the oral type-2 products remain a more attractive investment; however, they still face an uphill battle to get empagliflozin approved in the US in particular, as shown by the FDA’s decision not to approve the first of the class to be put forward – AstraZeneca's and BMS’ dapagliflozin. |
Top-line results have been announced by partners Boehringer Ingelheim (Germany) and Eli Lilly (United States) for four Phase III trials of their investigational sodium glucose co-transporter-2 (SGLT-2) inhibitor empagliflozin, intended for the treatment of patients with type-2 diabetes. As the partners report, in each of the four studies, the primary endpoint of a significant change in HbA1c (glycated haemoglobin) levels from baseline in comparison with placebo was met. The candidate SGLT-2 inhibitor was tested in four situations, and compared with placebo in each case – as monotherapy; as an add-on therapy to metformin and metformin plus sulfonylurea; as an add-on to pioglitazone and pioglitazone plus metformin; and with patients with mild, moderate, and severe renal impairment.
The partners reported that the incidence of adverse events were comparable for placebo and empagliflozin in either the 10mg or 15mg doses, while incidence of genital infections were more frequent with empagliflozin, in line with the results from the Phase II study. Both partners declared their satisfaction with the results, while confirming that detailed data disclosures for the studies will be presented at meetings and in publications during the course of 2013 and 2014. According to the Boehringer press release, the Phase III clinical trial programme for empagliflozin will involve the participation of more than 14,500 patients, and there will also be a major cardiovascular outcome trial.
Additionally, Boehringer Ingelheim – which is engaged in collaboration agreement with Eli Lilly on diabetes treatments – has announced that it will discontinue its involvement in the development of one of the products included in this collaboration agreement – the basal insulin analogue LY2605541. Boehringer cited independent strategic portfolio considerations as the reason for this decision, while it reaffirmed its commitment to the other products in the diabetes collaboration: empagliflozin, dipeptidyl peptidase-4 (DPP-4) inhibitor Trajenta (linagliptin) and the insulin glargine product LY2963016. As reported by The Wall Street Journal, Eli Lilly has announced that it will resume the development of the basal insulin analogue independently, and intends to go ahead with previously planned Phase II clinical trials.
Outlook and implications
Without adequate details of the four clinical trials, it is difficult to say just how significant the results may be at this stage. However, it is certain that Boehringer and Lilly are somewhat behind in the race to put an SGLT-2 inhibitor on the market, with AstraZeneca (United Kingdom) and Bristol-Myers Squibb (BMS, US) having already been granted marketing approval for Forxiga (dapagliflozin) in the European Union – although it was rejected by the US FDA due to safety concerns, with more assurances on safety requested – and Johnson & Johnson (J&J) unit Janssen currently waiting to hear from the FDA regarding its SGLT-2 inhibitor canagliflozin, following its new-drug application submission in December 2012.
Although SGLT-2 inhibitors have shown some considerable promise, even in comparison with the previous wave of novel oral type-2 diabetes treatments – DPP-4 inhibitors and incretin mimetics (see United States: 11 June 2012: ADA 2012 Highlights Include Canagliflozin Beating Januvia) – there are still concerns that the substantial investment in the development of these drugs, in part due to the heightened safety concerns of the FDA following the safety scandals surrounding the GlaxoSmithKline (GSK) oral type-2 diabetes product Avandia (rosiglitazone), will not be justified by the eventual returns. These concerns have resulted in the FDA's decision to request further safety data from AstraZeneca and BMS for their SGLT-2 inhibitor product, and a similar caution can be expected with the Janssen and Boehringer/Lilly submissions.
Another issue is the increasing number of products in the second-line treatment space for type-2 diabetes; SGLT-2 inhibitors will have to establish themselves in a market space in which some products, such as Merck & Co' s DPP-4 Januvia (sitagliptin) are already well-established on the market. However, with SGLT-2 inhibitors showing superior weight-loss performance, this may sway some in favour of them, although this is balanced by a higher incidence of infections in the case of SGLT-2 inhibitors.
Regarding Boehringer's decision to pull out of the development of the basal insulin analogue, this can be seen as the company's strategic assessment of this market segment being highly competitive, with little chance of making sufficient inroads into the market segment to justify continued investment; nevertheless, the future success of Boehringer and Lilly's oral type-2 diabetes products in an increasingly competitive and saturated market space is by no means guaranteed, either.