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.