Pharm Exec's 2012 Pipeline Report - Pharmaceutical Executive


Pharm Exec's 2012 Pipeline Report

Pharmaceutical Executive

Hyperlipidemia: CETP Inhibitors and More

We're still a few years away from knowing whether a new class of cholesterol drugs—CETP inhibitors—will actually reduce atherosclerosis, and resulting cardiovascular events, but analysts have not been shy about predicting blockbuster sales for Merck's anacetrapib and Roche's dalcetrapib. Despite Pfizer's failure with a first-in-class CETP inhibitor—torcetrapib—in 2006, Lilly is pursuing a fourth, evacetrapib, which produced comparable increases in HDL, and decreases in LDL based on a small, short-term Phase II study announced at an American Heart Association event in November. Fatalities related to hormone-induced hypertension that occurred during Pfizer's torcetrapib trials have so far been an isolated affair among CETP inhibitors. Evacetrapib is being tested as a stand-alone, as well as in combination with a variety of statins, and so far looks to be as efficacious as Merck and Roche's compounds, at a smaller dose.

Meanwhile, AMR-101, the lead candidate from Irish-based biopharma Amarin, got filed with the FDA in late November, with a PDUFA date scheduled for July. AMR-101 is a prescription-grade omega-3 fatty acid (aka ultraconcentrated fish oil) indicated for very high triglycerides, with Phase III data showing a statistically significant reduction in triglyceride levels, without significantly increasing LDL. A second Phase III trial tested the drug in combination with a statin, in patients with two or more lipid disorders, and met its primary endpoint based on the percentage change in triglyceride level from baseline compared with placebo. An outcomes trial on "reducing the first major cardiovascular events in an at-risk patient population," which hopes to test 8,000 patients for six years, is expected to commence enrollment by the end of 2011. Meekings says AMR-101 differs from GSK's Lovaza, another fish oil concentrate, by offering a better dosing benefit, and because Lovaza tastes a little fishy. More importantly, "[Amarin] is looking at the treatment of patients who are currently on statin therapy, a massive market ... if AMR-101 captures a small proportion of people on Lipitor, where hypertriglyceridemia is a problem, then sales potential is tremendous," says Meekings. Indeed, Thomson Reuters is bullish on ARM101, with predicted sales hitting $2.3 billion by 2016. "It's a one-of-a-kind drug with a very high margin potential, and a totally innocuous side effect profile," adds Selvaraju. "People have been taking omega-3 fatty acids for years."

Orphan Alert: lomitapide

Aegerion Pharmaceuticals' lomitapide, an orphan drug in development for homozygous familial hypercholesterolemia (HoFH), is expected to be filed with the FDA and the EMA this month, and expected to gain FDA approval in 2012. Patients with familial hypercholesterolemia, a genetic disorder, have extremely high cholesterol in their blood, and often die of heart attacks in their 30s and 40s. While genetic screening "often only finds one in a million patients that have mutations ... in the real world, physicians define patients with familial hypercholesterolemia according to other surrogate biomarkers like cholesterol level; they use phenotypic definitions of the disease, as opposed to genotypic definitions," says Joe Schwartz, managing director, biotechnology, at Leerink Swann. "We model for 3,000 patients in the US, as opposed to 300 ... which may even be conservative, given phenotypic definitions of high cholesterol and other risk factors for cardiovascular disease in the US." Schwartz predicts eventual sales of $450 million—a mini-blockbuster—and says Aegerion is currently "beating the bushes" with registries to identify prospective patients. Registries "are one of the aspects of orphan drugs that is positive for investors, because drug launches are often seeded with patients that were identified at the outset," instead of post-launch.

Respiratory: Taking a Breather

For patients, the biggest news in asthma and COPD is probably more money in the bank, as the Advair (GSK) and Singulair (Merck) juggernauts begin to lose patent protection. GlaxoSmithKline, however, has a plan: shift Advair users to a new combination called Relovair. "As Advair goes off patent, [Relovair] will allow GSK to have an aggressive switch campaign, and there's a huge market for that," says Meekings. Relovair, currently in Phase III, is comprised of the inhaled corticosteroid fluticasone furoate (aka Veramyst) and vilanterol trifenatate, a long-acting beta agonist (LABA). The selling point for the switch will most likely be Relovair's once-a-day dosing (Advair is twice-daily). Theravance contributed to the development of Relovair through a collaboration with GSK to investigate LABAs in combination asthma/COPD drugs. Novartis has a few products in the works for COPD, including the Seebri Breezhaler, which is preregistered for approval in Europe; FDA told Novartis in October that it needed more data to support the use of glycopyrrolate for COPD, which consequently postponed a planned submission by this year's end. FDA approved Novartis' Arcapta Neohaler (indacaterol inhalation powder) in July, and Eisai will co-promote Novartis' Onbrez Inhalation capsules (indacaterol maleate) as well as NVA-237 (glycopyrronium bromide) and QVA-149 (fixed-dose combo of indacaterol maleate and glycopyrronium bromide), should those get approved. "People want a better inhaler, and that's a very high bar for now," says Weintraub. If Novartis can prove glycopyrrolate is safe and effective—and better than the very good asthma and COPD drugs already on the market—it could put a little new wind in this category's sails.


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