2014 Pipeline Report: The Sprint to Value - Pharmaceutical Executive


2014 Pipeline Report: The Sprint to Value

Pharmaceutical Executive

Heart Failure: Possible Success

Patients entering emergency rooms in the United States are more likely to be there as a result of acute heart failure than for any other reason. In the last 25 years, heart failure incidence has increased by about 175 percent, and what's worse is that drug development in this high need area has been abysmal, says Martin Sullivan, executive medical director of cardiovascular medicine at INC Research, and a board certified internist and cardiologist. Heart failure has been an "arena of therapeutic futility...there have been probably 20 candidate compounds tested over the last 15 years, and we're zero for 20 on these compounds," says Sullivan.

That could change with Novartis's serelaxin, a peptide hormone currently under review in the United States and Europe. FDA granted Fast Track status in 2009, and Breakthrough Therapy status last summer; Sullivan says serelaxin could be a "home run" for heart failure. Citing the RELAX-AHF Phase III data, Sullivan says serelaxin "had a reduction in dyspnea, a small improvement in [hospital] length of stay, and most importantly, a significant reduction in re-hospitalizations and death in 90 days." Serelaxin is a recombinant form of human relaxin-2, a naturally occurring hormone; pregnant women release relaxin during labor, which causes ligaments to relax and become more flexible to facilitate childbirth. Using a hormonal treatment like serelaxin for heart failure is interesting because "it has so many different effects on so many different pathways," says Sullivan. "It effects inflammation, fibrosis, cell cyclin, it's a vasodilator, it does all kinds of things."

It could also make Novartis the proud parents of a new blockbuster for acute heart failure. Thomson Reuters predicts sales of roughly $1.2 billion by 2019, and serelaxin could receive European approval by this year's end. Seamus Fernandez, managing director of major and specialty pharmaceuticals at Leerink Swann, wrote in a recent analyst note that serelaxin's Breakthrough Therapy status did not confer an expedited FDA review of the drug, according to Novartis management, but the company expects a US approval in late 2014. Leerink Swann is predicting $1.3 billion in sales for serelaxin by 2020.

Sullivan also points to Acorda Therapeutics GGF2 candidate—a naturally occurring neuregulin or growth factor—and the results of an early stage trial, which improved some patients' ejection fraction by nine percent. Ejection fraction is a measure of how effectively the heart pumps blood. Like serelaxin, GGF2 is a peptide product with multifaceted effects in the body, including "cell cyclin, cell death, CNS effects...and it effects cell programming a little bit, potentially in vivo," says Sullivan. After a 24-hour infusion, patients given a higher dosage of GGF2 showed a heart function improvement at 28 days and 90 days. Acorda said it has discussed a new trial protocol with FDA for 2013, presumably a Phase II study, but http://ClinicalTrials.gov/ shows only a small Phase Ib double-blind study testing a single GGF2 infusion for safety and tolerability. This product may be further off, but Sullivan says if the data holds through Phase III, "that would be a major advance in heart failure."

Device Alert
Incidentally, the Chinese company Zensun is also testing a neuregulin drug candidate called Neucardin for chronic heart failure. A Phase II trial has been completed in the United States, and drug has been filed already in China. The company is currently enrolling a Phase III trials in the United States, but Phase II data was less impressive than Acorda's. However, a Zensun press release states that 678 people with chronic heart failure have been given Neucardin, and Phase II data demonstrated a "three to five percent placebo corrected improvement in left ventricular ejection fraction." SciClone Pharmaceuticals will market Neucardin in China, in a deal worth upwards of $30 million if Zensun meets its regulatory milestones. Forecasting for GGf2 and Neucardin is too speculative at this point to be meaningful, but if any drug candidate shows it can improve symptoms and survival in heart failure patients, the dollars will almost assuredly follow.

Last year's pipeline covered the PCSK9 inhibitors—notably Amgen (AMG 145) and Sanofi/Regeneron's (alirocumab) candidates, both of which have important Phase III data read-outs in 2014—but there isn't much new to report since last year aside from forecasts on both drugs getting reined in. Leerink Swann now estimates that AMG 145 won't quite reach blockbuster status by 2020, and Thomson Reuters scaled back alirocumab to just under $500 million by 2019. Credit Suisse still thinks AMG 145 will reach blockbuster status by 2020, and puts alirocumab's sales at $865 million in 2020. During its 3Q earnings report in late October, Pfizer announced a "major" Phase III program for its PCSK9 inhibitor, called bococizumab, according to an analyst note from Fernandez at Leerink Swann. Three is a crowd, so Pfizer tossing its hat into the PCSK9 ring can't be good news for Amgen and Sanofi/Regeneron.


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