In Roche's first research overview since integrating Genentech last year, management updated investors on several near-term oncology drugs and laid out plans for establishing itself as a player in the metabolic and cardiovascular disease markets. The drug maker outlined its early- to late-stage portfolio during an R&D day in New York on March 18.

Roche is targeting 16 new molecular entities for regulatory filing between 2010 and 2014, and of those, eight are in a heritage area, oncology. But four others are aimed at treating cardiovascular disease or diabetes, therapeutic areas in which Roche does not currently play.

Both are high-risk and costly areas of drug development, given the extensive clinical trials regulators demand to meet safety requirements, but they also represent lucrative money-making opportunities. If positive data emerges as Roche hopes, these four drugs may have a substantial impact on Roche's long-term growth trajectory.

Roche's nearest-term opportunity in this area rests with taspoglutide, a glucagen-like peptide-1 analogue being developed to treat type 2 diabetes, which Roche plans to file in 2011. The drug would compete with other GLP-1s on the market if it launches, including Eli Lilly/Amylin's Byetta (exenatide) and Novo Nordisk's Victoza (liraglutide), as well as a new long-acting form of exenatide that could be approved by FDA by that time (Also see "FDA's "Complete Response" Letter For Byetta LAR Isn't Too Onerous, Amylin Says" - Pink Sheet, 15 March, 2010.).

Roche is planning to present data from several Phase III clinical trials of taspoglutide at the American Diabetes Association Scientific Sessions in June, data that could provide more color about efficacy, tolerability and how it may stack up against the competition.

Roche Estimates Dalcetrapib Peak Sales Of CHF 5 Billion

The most significant commercial opportunity for Roche in the mid-term is the cholesterol drug dalcetrapib, a potential first-in-class cholesterol ester transfer protein inhibitor. CETP inhibitors work by increasing the "good" HDL-cholesterol instead of decreasing the "bad" LDL-cholesterol, which is how statins work.

Roche has high hopes for this drug. The company expects it could generate peak sales of CHF 5 billion ($4.7 billion), according to Chief Operating Officer, Roche Pharmaceuticals, Pascal Soriot. But dalcetrapib is part of a tainted class of medicines and, therefore, a drug investors are scared to embrace. Pfizer's CETP inhibitor torcetrapib met a notorious demise. The company's Phase III development program was halted early in 2006 due to higher rates of high blood pressure and a related increase in deaths in the treatment arm, an enormous failure that ultimately contributed to the Lipitor maker's decision to exit the cardiovascular disease market altogether.

Roche has spent the four years since the Pfizer setback studying the mechanism of action and evaluating the differences between dalcetrapib and torcetrapib - while trying to convince investors that dalcetrapib won't meet the same fate as torcetrapib too. The market opportunity is undoubtedly nudging Roche on. "If [dalcetrapib] does work, it would transform the company," Global Development and Chief Medical Officer Hal Barron said.

But even Barron seemed to be hedging his bets in opening the presentation on Roche's efforts in the cardiovascular market. "If we are shooting for really enormous opportunities in medicine...then we should expect to have some things that go the way we don't expect," he said. "We've had a lot of great successes, and we're going to have some failures as we swing for the fences."

In Phase II trials, the safety and tolerability of dalcetrapib held up with no increases seen in blood pressure. Dalcetrapib and torcetrapib have different mechanisms of CETP inhibition, Barron maintained. Roche is currently studying dalcetrapib in four Phase III trials, including an extensive outcomes study that is enrolling 15,600 patients with stable congestive heart disease with recent acute coronary syndromes. The company is targeting a regulatory submission for dalcetrapib in 2013.

Merck & Co. is also moving forward with development of a CETP inhibitor, anacetrapib, in Phase III studies.

The other two drugs in the cardiovascular/metabolic market in Roche's near-term pipeline are a renal sodium-glucose cotransporter 2 (SGLT-2) inhibitor being developed for type 2 diabetes and targeted for filing in 2013, and a dual agonist of peroxisome proliferator-activated receptors aleglitazar, for which Roche is targeting a filing in 2014. The company initiated a Phase III cardiovascular outcomes study for aleglitazar in the first quarter, with the study designed to enroll 6,000 patients with type 2 diabetes who have been hospitalized for acute coronary syndrome; treatment duration will run at least two and a half years.

Commercial Ramp Up Will Be Required

If taspoglutide and dalcetrapib get through the regulatory hoops, Roche will need to expand its commercial infrastructure to successfully launch the drugs. The company already has an 800-person sales force in the U.S. selling the osteoporosis drug Boniva , and that force would be directed toward taspoglutide.

The commercial move into the metabolic space will be a multi-pronged approach, Soriot said in a follow up interview. For an injectable agent like taspoglutide, he said, "We are going to target a more limited number of physicians, 60,000 to 70,000, so more targeted then we would have for an oral agent." Thus, Roche expects it would only need to add one new sales force, he noted.

"When we launch dalcetrapib, we have to expand further because there you really are talking about a variable set of physicians, 100,000 to 110,000," he said.

- Jessica Merrill (j.merrill@elsevier.com)

With One Foot Firmly Planted In Oncology, Roche Moves The Other Into CV/Metabolic

More from Archive

More from Pink Sheet