On to phase III for Esperion as FDA lifts hold

One piece of the Esperion Therapeutics puzzle has been put into place for 2015; the rest is up to the group's business development acumen.

The lifting of a partial clinical hold on its lead project, the cholesterol-lowering agent ETC-1002, clears the deck for phase III trials as it will allow for longer-term dosing in a space that demands data from a year or more of treatment. But for the full pivotal programme to be taken to completion, the Michigan-based group now needs the resources only a big pharma partner or buyer can provide.

Catalyst

Shares have risen 19% since Monday’s post-market announcement that the agent, which the FDA suspected might activate the peroxisome proliferator-activated receptor (PPAR), will be allowed to be dosed for longer than six months. It has been under that six-month constraint since 2011 to address FDA concerns about cancer risk.

As phase II has progressed Esperion has also been gathering carcinogenicity data from two-year rat and mouse studies. Monday’s announcement confirms that the cancer worries have eased, opening the way to bigger and longer trials.

ETC-1002 is a once-daily oral project that targets low-density lipoprotein cholesterol (LDL-C), the so-called “bad” lipid that is lowered by such existing therapies as statins or Zetia. The branded hyperlipidaemia space has been shrinking since the statin Lipitor lost patent protection, but it is due to undergo another transformation later this year when the biological PCSK9 agents alirocumab and evolocumab are due to be launched.

The Esperion pill is now set to be advancing in the wake of these two projects and, if successful, has the potential to become a more price-competitive product, not to mention preferable for patients who do not want to undergo the subcutaneous injections of the PCSK9 antibody class.

But, to be competitive, ETC-1002 needs to show that like the PCSK9 class it can demonstrate LDL-lowering capabilities both as monotherapy and on a backbone of currently prescribed drugs. The phase II programme has shown that it can do this against Zetia and Lipitor in small, limited-term trials, and most importantly has shown that it can perform well in statin-intolerant patients (Esperion rewards the faith of IPO investors, October 2, 2014).

The Zetia trial readout was a trigger for a $91.6m fund raising, to be added to a cash pile of $40.2m at September 30.

Two phase II studies remain to read out: an evaluation against placebo in patients with high cholesterol and hypertension, and another statin add-on trial.

Taking its shots

The fundraising is essential for preparing for and at a minimum beginning a phase III programme that the company says can start later this year with the lifting of FDA’s clinical hold.

It is doubtful that a company with a market capitalisation of a $1bn can undertake as massive a pivotal programme as Sanofi, Regeneron and Amgen have done with alirocumab and evolocumab – those agents have 26,000 and 42,000 patients enrolled in trials, with the largest lasting six years as the groups gather clinical outcomes.

What Esperion probably can afford is to design the trials and potentially initiate some limited-scale trials, such as those in familial hypercholesterolaemia or high-risk patients. These settings could involve hundreds of patients, rather than thousands.

The key to assessing ETC-1002’s full potential, however, lies in a collaboration or takeout. Sellside analysts covering the company have tagged a mid-year end-of-phase-II meeting with the FDA as a catalyst.

Esperion was bought and later spun out of Pfizer, the latter transaction having the goal of developing ETC-1002 and other lipid-modifying agents. With Pfizer seemingly in a buying mood, it must surely be keeping an eye on Esperion’s latest developments.

To contact the writer of this story email Jonathan Gardner in London at [email protected] or follow @JonEPVantage on Twitter