Alogliptin's Approval Woes
Alogliptin's Approval Woes
Sitagliptin continues to dominate the US market, and Merck continues to have a large sales force promoting the drug. Although saxagliptin is promoted by both AstraZeneca and Bristol-Myers Squibb, their promotional efforts have lagged recently, possibly in anticipation of their next diabetes drug, dapagliflozin. Linagliptin originally was promoted by Lilly in conjunction with the GLP-1 agonist exenatide (Byetta®, Amylin), but a split from Amylin now allows Lilly to focus on its DPP-4 inhibitor.
Takeda has had a series of cuts in their sales force, likely due to decreased use of pioglitazone (Actos®), which will soon become generic. Would Takeda have enough sales representatives in their diabetes division to inform physicians about alogliptin? Would they use a direct-to-consumer approach?
The one advantage Takeda has over its competition is that it still owns the patent to pioglitazone. As most combination pills are approved on the basis of bioequivalence, an alogliptin/pioglitazone combination could gain FDA approval at the same time as alogliptin alone. This combination pill is already available in Japan under the name Liovel®.
Adding a second agent to a patient's regimen by switching to a single combination pill (eg, switching from metformin to metformin/DPP-4) might seem to be a likely progression in diabetes management, but adding a DPP-4 inhibitor or a thiazolidinedione usually only achieves an additional 0.5% reduction in A1c. Thus, adding a second pill to metformin, such as alogliptin/pioglitazone, might appeal to clinicians, as the combination would have better efficacy than either agent alone.
In addition, with the technology used to make DPP-4 combinations -- the DPP-4 inhibitor is essentially sprayed onto metformin -- Takeda could be the first to market a triple combination pill, starting with ACTOplus met XR (pioglitazone/metformin).
A real game-changer could be the approval of dapagliflozin, which would be the first in a new drug class called SGLT2 inhibitors. Dapagliflozin is just as effective as the DPP-4s and also lowers blood pressure and contributes to weight loss. Although the FDA declined to approve this drug last year because of safety concerns, its eventual availability could change the diabetes landscape. The drug is poised for approval in Europe this summer.
Dapagliflozin likely will be available in a combination formulation with metformin, and one could imagine initiating therapy with such a combination. However, as in the previous scenario, adding alogliptin/pioglitazone to dapagliflozin/metformin still would make sense, given their complementary mechanisms of action. This would achieve a 2-pill, 4-drug regimen without the use of a sulfonylurea.
If it is approved, alogliptin would be the fourth DPP-4 inhibitor on the market and is similar to other drugs in that class. As such, alogliptin could struggle to find a place in the type 2 diabetes armamentarium of most clinicians. Although alogliptin as monotherapy may not excite prescribers, the combination of alogliptin with pioglitazone in a single pill could present a valuable new option as add-on therapy to metformin and possibly to dapagliflozin if the latter drug becomes available.
Elbowing Into the Market
Sitagliptin continues to dominate the US market, and Merck continues to have a large sales force promoting the drug. Although saxagliptin is promoted by both AstraZeneca and Bristol-Myers Squibb, their promotional efforts have lagged recently, possibly in anticipation of their next diabetes drug, dapagliflozin. Linagliptin originally was promoted by Lilly in conjunction with the GLP-1 agonist exenatide (Byetta®, Amylin), but a split from Amylin now allows Lilly to focus on its DPP-4 inhibitor.
Takeda has had a series of cuts in their sales force, likely due to decreased use of pioglitazone (Actos®), which will soon become generic. Would Takeda have enough sales representatives in their diabetes division to inform physicians about alogliptin? Would they use a direct-to-consumer approach?
Combination Solutions
The one advantage Takeda has over its competition is that it still owns the patent to pioglitazone. As most combination pills are approved on the basis of bioequivalence, an alogliptin/pioglitazone combination could gain FDA approval at the same time as alogliptin alone. This combination pill is already available in Japan under the name Liovel®.
Adding a second agent to a patient's regimen by switching to a single combination pill (eg, switching from metformin to metformin/DPP-4) might seem to be a likely progression in diabetes management, but adding a DPP-4 inhibitor or a thiazolidinedione usually only achieves an additional 0.5% reduction in A1c. Thus, adding a second pill to metformin, such as alogliptin/pioglitazone, might appeal to clinicians, as the combination would have better efficacy than either agent alone.
In addition, with the technology used to make DPP-4 combinations -- the DPP-4 inhibitor is essentially sprayed onto metformin -- Takeda could be the first to market a triple combination pill, starting with ACTOplus met XR (pioglitazone/metformin).
Introduction of Dapagliflozin
A real game-changer could be the approval of dapagliflozin, which would be the first in a new drug class called SGLT2 inhibitors. Dapagliflozin is just as effective as the DPP-4s and also lowers blood pressure and contributes to weight loss. Although the FDA declined to approve this drug last year because of safety concerns, its eventual availability could change the diabetes landscape. The drug is poised for approval in Europe this summer.
Dapagliflozin likely will be available in a combination formulation with metformin, and one could imagine initiating therapy with such a combination. However, as in the previous scenario, adding alogliptin/pioglitazone to dapagliflozin/metformin still would make sense, given their complementary mechanisms of action. This would achieve a 2-pill, 4-drug regimen without the use of a sulfonylurea.
The Bottom Line
If it is approved, alogliptin would be the fourth DPP-4 inhibitor on the market and is similar to other drugs in that class. As such, alogliptin could struggle to find a place in the type 2 diabetes armamentarium of most clinicians. Although alogliptin as monotherapy may not excite prescribers, the combination of alogliptin with pioglitazone in a single pill could present a valuable new option as add-on therapy to metformin and possibly to dapagliflozin if the latter drug becomes available.