- Takeda has submitted its once-weekly DPP-4 inhibitor trelagliptin in Japan; the drug appears to be stalled in phase 2 in the US and EU (last study completed in 2008).
- The performance of trelagliptin in Japan (if approved) could provide clues on how other once-weekly agents (such as Merck’s phase 3 MK-3102) will fare on the broader market.
This morning, Takeda announced that it submitted its once-weekly DPP-4 inhibitor trelagliptin to Japanese regulatory authorities, marking the first submission of a once-weekly DPP-4 inhibitor in a major market. This was in line with management’s guidance during the JP Morgan Healthcare Conference in January for a submission in the “next few months.” The company press release states that once-weekly dosing is expected to improve patient adherence to treatment, a key goal in diabetes therapy. ClinicalTrials.gov shows that the drug’s two most recent (phase 2) studies in the US and EU were completed in early 2008, raising uncertainty over whether Takeda still plans to advance the compound towards submission outside Japan. DPP-4 inhibitors have seen particular success in Japan (where limited early evidence indicates that the class might have greater efficacy than in Caucasian patients), and we wonder if Takeda sees enough of a difference in trelagliptin’s value proposition inside and outside Japan to consider limiting the product to Japan and eschewing the costly phase 3 / CVOT development process in the US. We would certainly understand if that were the case, though we also think that if trials are long enough, cardioprotection with incretins agents may be possible – although from what we hear from the diabeterati, this would be more likely to be seen with GLP-1 than DPP-4 inhibitors. We do have the impression after discussions with KOLs that much larger trials of shorter duration are not likely to be fruitful in showing positive benefits. Historically, of course, the higher US profitability made it worthwhile for companies, though there has certainly been more pricing pressure of late.
Merck, manufacturer of the current market-leading DPP-4 inhibitor Januvia (sitagliptin), is also working on its own once-weekly compound, MK-3102 (omarigliptin; phase 3 in the US and EU). The company has characterized MK-3102 as an important compound that could facilitate earlier initiation of DPP-4 inhibitor therapy (See our Merck 3Q13 Report for more details). A Merck-sponsored discrete-choice study on once-weekly administration presented at last year’s ADA (see page 10 of our ADA 2013 Treatment Strategies and Algorithms Report) found that while 67% of patients (especially the young and treatment-naïve) preferred once-weekly to daily administration, the average patient was only willing to pay $5.86 per month for a once-weekly agent. We think that payers might see a higher value differential, given the downstream costs associated with poor adherence. Once-weekly dosing could be of particular value in pediatric patients and the newly-diagnosed, for whom adherence barriers are particularly high. India-based Zydus Cadila is also developing a once-weekly DPP-4 inhibitor, ZYDPLA1, which entered phase 1 late last year. Although trelagliptin will not be debuting in the US and EU any time soon, its performance in Japan (if approved) could provide insight into how once-weekly oral agents could change the dynamics of the oral antidiabetic drug market.
-- by Manu Venkat, Jessica Dong, and Kelly Close