Wednesday, April 23, 2014

How Malmo may turn around Cardiome’s BRINAVESS

June 25, 2013 by · Leave a Comment 

In the midst of unwinding a blockbuster collaboration and licensing deal with Merck (NYSE:MRK) last fall, Cardiome Pharma (NASDAQ:CRME; TSX:COM) received permission to meet all of Merck’s country managers in Europe where it had been selling Cardiome’s intravenous BRINAVESS for the rapid conversion of recent onset atrial fibrillation (AF) to normal sinus rhythm in adults.

Dr. William Hunter

Dr. William Hunter

“That trip changed my view about BRINAVESS,” CEO Dr. William Hunter says in an interview with BioTuesdays.com.

“In the wake of losing the Merck deal and getting the drug back, we could have sold off the BRINAVESS asset, distributed the proceeds to shareholders and wound up the company,” he admits. “But there are many examples where a product that wasn’t a good Big Pharma drug turns out to be a good Small Pharma drug, and we felt this might be one of those cases.”

The collaboration traces its roots to April 2009, when Merck agreed to develop and commercialize BRINAVESS, gaining exclusive rights to an IV formulation outside of North America, and exclusive global rights to an oral formulation for the maintenance of normal heart rhythm in patients with AF. The IV formulation was approved and launched in Europe by Merck in 2010.

But in 2012, everything went wrong for Cardiome. In March, Merck discontinued development of the oral version of BRINAVESS, and in September, it gave notice to terminate the license agreements for the drug. The company’s stock price plummeted, Dr. Hunter moved into the executive suite from the board, the work force was slashed by 85% and spending was cut.

But two developments near the end of 2012 convinced Dr. Hunter that Cardiome could make BRINAVESS succeed with a focused marketing plan.

First, the European Society of Cardiology issued new AF guidelines last fall, recommending BRINAVESS as a first-line therapy in haemodynamically stable patients with moderate or no structural heart disease. “This was a significant piece of the puzzle, because the guidelines came out a couple of days before Merck stopped marketing the drug for us,” Dr. Hunter recalls.

BRINAVESS:  First-line Therapy in European Society of Cardiology Atrial Fibrillation Treatment Guidelines

BRINAVESS: First-line Therapy in European Society of Cardiology Atrial Fibrillation Treatment Guidelines

The second piece of the puzzle followed an analysis of Merck’s data about the clinical usage of BRINAVESS and hospital sales patterns.

“What we saw was that in some places, hospitals were using a ton of BRINAVESS, and in other places, it wasn’t being used at all,” he remembers. “Clearly, somebody had figured out how to make BRINAVESS fit with their treatment practices.”

One of the places with a high usage of BRINAVESS was a hospital at Malmo, Sweden.

Dr. Hunter, a former practicing physician, says that when doctors at Malmo treated AF patients with BRINAVESS within the first 24 hours of being diagnosed with AF symptoms, they were able to convert nearly 80% of patients to normal sinus rhythm, a level well above the drug’s label of a 50% conversion rate, within seven days of AF onset. And within the first 48 hours, the success level was about 70% at Malmo.

That, in turn, reduced the need for anti-coagulants and direct current cardioconversion, an electrical stimulation procedure to restore normal heart rhythm that also requires the presence of an anesthesiologist. “Even if a patient wasn’t successful with BRINAVESS, they were moved to the DC cardioconversion unit, without losing very much time,” Dr. Hunter offers.

“The total treatment time in Malmo from the time that a patient arrives at hospital to discharge was about 3.5 hours when treated with BRINAVESS, compared with about 12 hours with DC cardioconversion,” Dr. Hunter says. And the total treatment cost with BRINAVESS was about half of DC cardioconversion, he adds.

brivaness“So, now we thought we had a story to tell – new cardiology guidelines in Europe and cost savings of time in the ER,” he points out. “If doctors use BRINAVESS in the right way, you get really good results, and there’s a strong economic reason to use the drug, but you must understand how.”

More than 10,000 patients have been treated in Europe with BRINAVESS for recent onset AF and post-cardiac surgery AF, its two indications. “So we are not dealing with a broken asset here,” Dr. Hunter contends. “You start a patient on IV plus BRINAVESS in the ER, close the curtain, and come back in 10 minutes, and most of the time, the patient is out of AF. That’s an attractive option in a busy ER.”

Dr. Hunter suggests there were probably several reasons that contributed to Merck’s lack of success selling BRINAVESS. For one thing, the Merck sales staff doesn’t specialize in hospital calls but has more of an in-office sales focus, “so maybe, we were marketing to the wrong cardiologists.” In addition, he says BRINAVESS was sold alongside lipid-lowering drugs and hypertensives. “So it wasn’t a focused call-point by a Merck sales rep.”

In March 2012, Merck discontinued development of the oral formulation of BRINAVESS, which was ready for Phase 3 testing, based on an assessment of the regulatory environment and projected development timeline.

After concluding his swing through Europe at the end of last year, Dr. Hunter says he told the Cardiome board that he’d rather have “20 sales reps that wake up in the morning and only worry about how to sell BRINAVESS instead of 150 sales reps where the drug is number three, or four, or five in a rep’s bag.”

And after concluding debt restructuring talks with Merck, Cardiome had $25-million, or two years of cash, at its current burn rate. “If our burn rate selling BRINAVESS runs around one million euros a month in Europe and we can reach sales of one million euros a month in two years, we will have changed the business destiny of Cardiome,” he contends.

Cardiome expects to have its sales force fully engaged before the end of a one-year sales transition with Merck this September. Quintiles (NYSE:Q) has been retained for back-office administration and management for Cardiome’s sales and marketing division.

Markets Where BRINAVES will be Sold Through a Direct Sales Force (In countries without a direct sales force, product sales will be conducted through distributors)

Markets Where BRINAVES will be Sold Through a Direct Sales Force (In countries without a direct sales force, product sales will be conducted through distributors)

Dr. Hunter figures the drug has a market potential of $50-million to $100-million a year in Europe and some $250-million a year in the U.S.

As part of unwinding the collaboration, Merck recently returned the investigation new drug application for IV BRINAVESS in the U.S. “We’re in the process of digging through the IND to understand the FDA’s concerns,” he says, adding that he hopes to have a path forward for BRINAVESS in the U.S. by the end of 2013. Naturally, we’ll show the FDA our data on the more than 10,000 patients that have already been treated in Europe. And the more IV we can sell in Europe, the better our chances are of getting the IV into the U.S.”

Cardiome: Commercial Stage Company with a Treatment for Atrial Fibrillation

Cardiome: Commercial Stage Company with a Treatment for Atrial Fibrillation

Dr. Hunter describes the oral formulation of BRINAVESS as “a Phase 3-ready product in search of funding,” pointing out that Merck has already manufactured all of the tablets needed to begin a pivotal trial. But before Cardiome can even begin discussions to ink a development partner, he figures the company needs to prove it can create a thriving market for the IV in Europe.

“The differences between with us and other biotechs is that we have the ability to generate cash. I don’t want to start making predictions, but I think this is a better drug than people realize.”

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