Boehringer/Lilly To Price Tradjenta On Par With Rival DPP-4 Inhibitors

Boehringer Ingelheim GMBH and Eli Lilly & Co. are likely to play up simplicity of dosing for the just-approved DPP-4 inhibitor Tradjenta (linagliptin) in a launch planned for the end of May, and expect to price the drug on par with others in the class.

Linagliptin was approved May 2 at a 5 mg dose as an adjunct to diet and exercise for improving glycemic control in patients with type 2 diabetes (Also see "Boehringer/Lilly's Linagliptin Approved: Can Renal Flexibility Unlock The DPP-4 Market?" - Pink Sheet, 2 May, 2011.).

Drugs in this class inhibit DPP-4, an enzyme that breaks down the incretin hormones GLP-1 and GIP that are involved with regulating blood sugar.

Sales staff are being trained as Boehringer and Lilly are gearing up for a joint commercial launch of Tradjenta in the U.S. that hopefully will be ready for roll-out at the end of May, said Wa’el Hashad, VP of U.S. cardiovascular and metabolic disorders at Boehringer, in an interview.

Linagliptin will probably cost the same as rivals Januvia and Onglyza.

The product’s price has not been set, but Hashad said he expects that it will be in line with other branded drugs in its class.

Tradjenta will become the third DPP-4 inhibitor to hit the U.S. market. Merck & Co.’s Januvia (sitagliptin) is by far the market leader with more than $1 billion in sales for the first quarter of 2011, including the line extension product Janumet (sitagliptin/metformin). Bristol-Myers Squibb/AstraZeneca were second to market with Onglyza (saxagliptin), and the metformin combination product Kombiglyze. But those products had combined sales of only $81 million in the first quarter of 2011.

Januvia’s wholesale acquisition cost unit price is $6.76, while Onglyza’s WAC unit price is $6.11.

Linagliptin: Playing On Simplicity

Linagliptin’s sponsors in the past have noted the drug has value as a safe option for renally impaired patients, because very little of the drug is excreted through the kidneys.

According to the Tradjenta label, no dose adjustment is recommended for patients with renal impairment.

Januvia is approved at three doses – 100 mg, 50 mg and 25 mg – with adjustments made on the basis of renal function, which needs to be monitored. Januvia’s labeling also has a warning about post-marketing reports of acute renal failure.

And Onglyza is approved at two doses, 5 mg and 2.5 mg, also with renal function monitoring.

But for Tradjenta, a focus on the renally impaired patient population would limit the market from the outset.

BI's Hashad stressed that linagliptin is approved for and is a good option across the spectrum of patients with type 2 diabetes – whether patients have normal kidney function or moderate-to-severe renal disease.

The program supporting approval included studies of the drug as a stand-alone therapy and in combination with a range of other type 2 diabetes drugs including metformin, glimepiride and pioglitzaone. BI has completed a study of a fixed-dose combination with metformin and a trial of a fixed combination with pioglitazone is well under way.

Tradjenta also offers simple dosing, because the drug is given at the same dose as a monotherapy or with a range of other diabetes treatments, Hashad explained.

Dosing also does not need to change according to renal function as disease becomes more severe. Linagliptin is the first in its class to be approved at one dosage strength, so there is only one dose to remember for all patients, he noted.

Though Tradjenta and Onglyza (which only needs one downward dosing adjustment) have the dosing advantage over Januvia, the way they are metabolized means more potential for drug interactions.

Onglyza is metabolized by the CYP system and is therefore affected by CYP agonists.

Its label warns that co-administration with strong CYP3A4/5 inhibitors, such as the antifungal ketoconazole, significantly increases saxagliptin concentrations. If these drugs are being taken, a lower 2.5 mg dose of Onglyza should be given, according to the label.

Tradjenta is a P-glycoprotein/CYP 3A4 inducer. Labeling states that its efficacy may be reduced when administered in combination with a strong P-gp or CYP 3A4 inducer, for example, with the antibiotic rifampin.

Januvia, in contrast, is not metabolized via the CYP system.

Elbowing Into The DPP-4 Market

As a whole, the DPP-4 class has sales of $3.9 billion in 2010, worth about 16% of the total worldwide diabetes drug market, according to Cowen and Company’s Therapeutic Categories Outlook Report from March. Sales for the class are expected to rise to $7.8 billion in 2015, or 20% of the total diabetes market at that time,

Cowen analysts note that the firm’s physician consultants believe there is little difference between the DPP-4 inhibitors and “therefore much will depend on commercial prowess and formulary access.” Cowen has forecast sales of $100 million in sales for linagliptin in 2012 and $400 million in 2015.

Though linagliptin has differentiated pharmacokinetics, the drug is late to the market, the analysts commented. But it likely won't be the last – in addition to Januvia and Onglyza, several other DPP-4 inhibitors are still in development.

Takeda Pharmaceutical Co. Ltd.’s alogliptin received a “complete response” letter in the U.S. and the company has been asked to do a cardiovascular outcomes study (Also see "Takeda's Alogliptin Suffers Major Setback, Delaying Drug Launch Until 2012 Or Later" - Pink Sheet, 29 Jun, 2009.).

Novartis’ Galvus (vildagliptin) is approved outside the U.S. but was not approved in the U.S. due to safety signals.

Other DPP-4 drugs in development include Glenmark Pharmaceuticals Ltd.’s GRC 8200 and Kyorin Pharmaceutical Co.’s KRP-104, both in Phase II. Pfizer Inc. has PF-4971729 in Phase I.

A successful launch of a DPP-4 drug is heavily dependent on good marketing.

With so many others hoping to reach the market, competition will be fierce, especially given the rapid adoption of DPP-4 inhibitors and the expanding diabetes population. “Linagliptin may capture incremental market share, although its success will likely depend on Lilly’s ability to market,” Cowen analysts observed.

The commercial launch will be run jointly by Lilly and Boehringer. Lilly is a veteran in the diabetes space and already has established relationships with doctors that could help pave the way for a linagliptin launch, the companies say. Sales reps will be targeting both primary care physicians and specialists.

Hashad also noted that the plan is to go beyond medication and offer related services to patients to help ensure treatment is successful. For example, patients will be given the option to enroll in a program that encourages adherence to prescribed medication regimens. But for now, at least, no consumer ad campaigns are in the works.

As for payers, Hashad pointed out that Boehringer has recent experience gaining access to formularies through its launch of the novel anticoagulant Pradaxa (dabigatran) for stroke prevention in atrial fibrillation. In the first months on the market, the drug had preferred status for one-third of covered lives in the U.S. (Also see "With Pradaxa On The Rise, Medco Gathers Evidence On Warfarin Diagnostic Testing" - Pink Sheet, 7 Mar, 2011.).

Aware of insurance processes and timetables, the companies are planning to offer copay assistance to help offset out-of-pocket costs to patients while the drug is being reviewed by payers, Hashad said. It’s unclear whether this will continue once payers have made their determinations on Tradjenta. Financial assistance will also be available for patients who meet certain poverty eligibility requirements, Hashad said.

By Emily Hayes