Off to Phase IV for Letairis® and the Market for Volibris®

Among the core assets that Gilead (Nasdaq: GILD) acquired from Myogen in 2006 for $2.5B was Letairis® (ambrisentan), for the treatment of pulmonary arterial hypertension (PAH), which was then approved by the FDA in mid 2007. After about a quarter in the market Gilead has initiated a Phase IV, randomized, double-blind, placebo-controlled study evaluating Letairis® in patients with PAH who have failed to demonstrate an optimal response to sildenafil monotherapy (Viagra® is not just for ED ya know…). The primary endpoint of this study, known as Athena-1, is the change from baseline in pulmonary vascular resistance (the resistance to blood flow caused by constricted lung blood vessels) following 24 weeks of treatment. The long-term safety and efficacy measures will be examined for up to one year. There are additional planned follow-on Phase IV studies through 2009.

Folks around town may recall that GlaxoSmithKline (NYSE: GSK) owns the rights to commercialize ambrisentan for PAH in territories outside of the US. Recently GSK announced that the European Commission issued a marketing authorization for ambrisentan, under the trade name Volibris®, for the treatment of PAH in patients to improve exercise capacity, and the European product launch is now scheduled for 3Q08. Very exciting global news that can trace its roots back to Colorado! Naturally we will be closely tracking performance of Letairis® and Volibris® in the coming months and years

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Michael Bristow, M.D., Ph.D. Wins 2008 PhRMA Award

Congratulations to Michael Bristow, M.D., Ph.D., the S. Gilbert Blount Professor of Medicine at University of Colorado, Head of Cardiology, Co-director of the University of Colorado Cardiovascular Institute, co-founder of Myogen (acquired by Gilead (NASDAQ: GILD), founder of ARCA Discovery and now add to that list winner of the Pharmaceutical Research and Manufacturers of America (PhRMA) 2008 Discoverers Award - Clinical Trial Exceptional Services Award. The distinguished award was given for discoveries made in the early 1980’s where Dr. Bristow found the failing human heart was subjected to harmful amounts of increased adrenergic activity, and the logical therapeutic response to that activity was beta-blockade; as well as for being the Principal Investigator and Chair of the Phase II and Phase III trials for Coreg (carvedilol) where Dr. Bristow’s work also helped to characterize the receptor and molecular profiles of the drug in the human heart. Coreg a medication by GlaxoSmithKline (NYSE: GSK) was the first beta-blocker approved by the FDA for the treatment of heart failure.

PhRMA represents the country’s leading pharmaceutical research and biotechnology companies, which are devoted to inventing medicines that allow patients to live longer, healthier, and more productive lives. PhRMA companies are leading the way in the search for new cures. PhRMA members alone invested an estimated $43 billion in 2006 in discovering and developing new medicines. Industry-wide research and investment reached a record $55.2 billion in 2006.

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Gilead Racks Up Quarterly Record

Gilead (NASDAQ: GILD) announced total revenues for 3Q07 of $1.06B, up 41% percent compared to total revenues of $748.7MM for 3Q06, along with record product sales of $962MM, up 44% over 3Q06! An amazing 90-day run, but what I am most interested in is how is Letaris® (ambrisentan) faring?

Now don’t quote me here because I am unable to recall/validate my sources (and I feel awful about that) but from what I have heard that with a field sales team focusing on large PAH centers Letairis® did about $6MM in its first quarter of sales and a forecast of ~$15MM for '07. The parity pricing with rival Actelion Pharma's Tracleer® (~40K/yr) has aided with reimbursement by Medicaid in 49 states, a strong label, and 9 of the top 20 managed care plans have given approval; combine these elements and Letairis should have a potent 2008 and aid a lot of people in the process. After perusing some of the PAH message boards this appears to be the tone…

"it [Letairis®] is doing wonders. I didn’t feel that way with Ventavis like many said I would but when I added Letairis I feel great. I am all over the house cleaning and playing with my kids and walking to the stores even Walmart. I'll let you know how my six minute walk and echo or rhc come out because I am doing so well they want to check those lovely numbers because that’s what counts. I hope it works for you as well as its doing for me at this point. I am a class 3 but by me just walking 2 minutes my sats didn’t drop and I wasn’t out of breath, he says its possible I'm a class 2 which would be great."

"It is amazing how much better I feel. Some days I feel almost normal. Less side effects for me than the Tracleer."

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FDA Approval for Letairis (Ambrisentan)!!!

You can hear the champagne corks popping from Westminster, CO to Foster City, CA as the FDA late Friday approved Gilead's (Myogen) Letairis® (ambrisentan) for the treatment of pulmonary arterial hypertension (PAH). There are up to an estimated 90,000 people in the US suffering from PAH, a disease where blood pressure is raised due to constricting lung vessels which may lead to heart failure. Letairis® is an endothelin receptor antagonist, and works by relaxing the blood vessels. Plans are to launch US sales this week and via a co-marketing agreement with GlaxoSmithKline filing for approval for ROW sales and marketing are underway.

Letairis® approval is certainly a feather in the cap for the Colorado bio-ecosystem. The people, the science and the supporters worked long (an understatement) and hard (another understatement) to bring this drug to market. It will be exciting to see if this talented group of individuals will roll up their sleeves and do it again. That is where the true magic happens towards building a vibrant biocluster filled with serial entrepreneurs mentoring to first timers.

Ambrisentan Moving Closer to Approval

Happily tracking the progress of Gilead Sciences, Inc. (NASDAQ: GILD) Ambrisentan asset; for the treatment of pulmonary arterial hypertension. Gilead’s recent announcement that the FDA has accepted for filing and granted a priority review for the NDA is exciting news for the Colorado bio-scape. This approval may result in an accelerated review with an expectation of a 18 June 2007 review date. Recall that Gilead recently acquired Westminster, CO based Myogen for $2.5B.

Myogen: Darusentan Enters Phase III

Myogen, Inc. (NASDAQ: MYOG) now has two candidates in Phase III trials, Ambrisentan and now Darusentan. The Darusentan trial will evaluate patients with resistant hypertension (RHTN). RHTN is the "the failure to achieve goal blood pressure in patients who are adhering to full doses of an appropriate three-drug regimen that includes a diuretic."

The primary objective of the trial is to determine if Darusentan is effective in reducing systolic blood pressure in resistant hypertension patients currently treated with full doses of four or more antihypertensive medications, one of which is a diuretic. The primary endpoint of the trial is change from baseline to week 14 in systolic blood pressure as compared to placebo.

Mayhem at Myogen?

So what the heck is going on at Myogen today?

The company announced that ambrisentan met its primary goal of helping people increase the amount of exercise they could do, and doing so without hurting their livers. Two great data points. Good news right? Share price zooms right? Well good news but not good enough as MYOG spent the day heading to a three month low on the day they also reported a big BUT…but the drug failed to significantly increase the time to clinical worsening observed in that study population.

One may view this pull back, based essentially on the failure to live up to the rock-star like data that ambrisentan had previously reported, as an entry opportunity to take a position or perhaps some dollar-cost averaging. (Note: this is not investment advice, I am not a pro nor do I plan one on TV).

Expectations and pressures are seemingly so high it is important, to the extant that it is possible, to put blinders on to what the street is saying and just drive the bus to an approved product. Some are saying ambrisentan, given todays report, that it won't take as much market share as previously thought from a rival drug Tracleer, from Switzerland-based Actelion. I say what if it does?

More Good News for Myogen

The FDA has granted Fast Track status for Myogen's ambrisentan, currently in Phase III clinical trials. This designation is aimed to expedite the review process.

The FDA designated ambrisentan as a Fast Track product for the following reasons:

1. Ambrisentan is intended to treat PAH, a life-threatening, progressive, and
incurable disease of the pulmonary vasculature.
2. The ambrisentan development program has been designed to address the unmet medical needs of patients with PAH, by demonstrating the following:

a. Ambrisentan has the potential for improved effects on exercise capacity, an efficacy measure that has been shown to correlate with and be prognostic of long-term survival.
b. Ambrisentan appears to delay the clinical worsening of PAH, a progressive and ultimately fatal disease.

Myogen Partners with GlaxoSmithKline

Myogen signed off on a two-tiered relationship with GlaxoSmithKline (GSK) whereby first, commercialization rights to ambrisentan have been licensed to GSK for all territories ex-US and secondly, Myogen will now be responsible for marketing and distributing GSK’s Flolan (for the treatment of primary pulmonary hypertension) in the US.

Myogen President and CEO J. William Freytag noted, “The Flolan distribution agreement is expected to underwrite the development of our own commercial organization and marketing and field selling expertise in PAH, well in advance of the potential launch of ambrisentan. We believe this strategic development will accelerate our understanding of customer needs, reimbursement opportunities and market dynamics in general."

Myogen is set to receive a $20M upfront payment for the ambrisentan license agreement and may be eligible for an additional $80M in milestone payments along with stepped royalties on product sales. Flolan agreement details to follow.

Myogen Getting Lean and Mean

Myogen, Inc. (Nasdaq: MYOG) has sold its wholly-owned European subsidiary Myogen GmbH for $6.1 million to Wulfing Holding GmbH. The deal centers around a sublicense for rights to Perfan® I.V. (intravenous enoximone) in markets outside North America, from which the former parent will continue to receive a royalty on future net sales.

Shedding this particular asset should enable a laser sharp focus upon Myogen’s development-stage products, ambrisentan and darusentan.

J. William Freytag, President and Chief Executive Officer, will present a corporate overview at the NASDAQ US Small Cap Conference to be held in London, 7 February.

Myogen Announces Positive Phase III Results

Myogen announced today that Ambrisentan®, for pulmonary arterial hypertension, met the primary efficacy endpoint and several strategic secondary endpoints in this first Phase III trial. Results are expected shortly, in 1Q06, on an additional Phase III study. To date Ambrisentan® has demonstrated:

• Improvement in exercise capacity
• Improvement in time to clinical worsening
• An apparent survival benefit when compared with predicted survival based on the NIH
Registry formula
• Effectiveness with once-daily dosing and the potential for dose flexibility
• Low incidence and severity of liver function test abnormalities at all doses
• No apparent drug-drug interactions with warfarin-type anticoagulants

Wall St. is certainly responding favorably to the announced results as well as the share price has jumped nearly 68%, up 9.33 to $28.05 over Friday’s close of $19.27. Here is a link to today’s web cast if you are interested in hearing more.

Myogen is Hunkering Down

Three cheers for Myogen (MYOG).

The company reported yesterday that the enoximone program, for the treatment of advanced stage chronic heart failure, has been terminated as a result of their two phase III trials failing to demonstrate a statistically significant benefit for any of the three co-primary endpoints.

Despite the news something needs to be said for the talented management team, led by J. William Freytag, Mike Bristow and Joe Turner, for creating a richly diverse portfolio that though disappointed by the enoximone results Myogen will now hunker down and focus its attention on not one but two other late-stage clinical programs.

Two phase III trials were initiated in early ’04 with ambrisentan, for the treatment of patients with pulmonary arterial hypertension, and in July ’04 a phase IIb trial commenced for darusentan, an oral therapy for patients with uncontrolled hypertension. In addition, the company currently markets Perfan® in eight European countries to treat patients with acute decompensated heart failure and, also boasts a robust research and discovery program in cardiac signaling, fetal genes, cardiogenomics & cardioproteomics and, Myogen can also lay claim to perhaps the world’s largest heart tissue bank.

A true test of a champion is when knocked down to get right back up and keep fighting. Myogen not only has plenty of fight left in her but also plenty of cash to fund working capital requirements and capital expenditures through deep into 2006. But don’t just take my word for it – Wachovia Bank also released yesterday their upgrade of Myogen from market perform to outperform.