We have seen a device approach to dealing with hypertension and it’s fair to say the reality didn’t live up to the hype.
The idea was to target nerves in the renal artery and disrupt them by delivering low-level radio frequency from a pulse generator using a catheter. Initial good results, grand acquisitions all preceded shocking news: the therapy didn’t really work as Medtronic found out in January 2014. Soon after, the-then Covidien also bowed out of the renal denervation market citing slow growth in Europe. Medtronic is still in the process of a reset with the launch of a new trial in April 2015, but no one appears to be holding their breath. Other approaches to hypertension that use neuromodulation as a way to manage high blood pressure don’t appear to have succeeded either.
Meanwhile, a device startup that just came out of stealth mode believes it has hit upon a winning combination for a device alternative to blood pressure medication: a juiced up pacemaker. BackBeat Medical, based in New Hope, Pennsylvania, has developed a device called Moderato that is intended for people who need a pacemaker and also take medication for hypertension. The pacemaker has a proprietary algorithm — Programmable Hypertension Control — that controls the heart and the force or pressure it puts out by pumping.
Darren Sherman, co-founder, director, BackBeat Medical
“We’re not doing neuromodulation, we’re not doing neurostimulation, we’re not doing renal denervation,” explained Darren Sherman, co-founder of Backbeat Medical, in an interview before the company presented results of a small study at the European Society of Cardiology’s annual meeting in Rome on Sunday. “What we are doing is we’re using the pacemaker function to adjust the way the heart beats that puts out less pressure.”
Backbeat’s CEO went further to explain why previous efforts at managing hypertension using renal denervation and neuromodulation (the latter way was adopted by Minnesota-based CVRx) ended in failure. They were way too complex and assumed knowledge about how nerves affect blood pressure.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
Yuval Mika, CEO of BackBeat Medical
“You need to understand what is the connection between what you are doing and the activation of the nerves, which is a big leap, not something that’s simple to understand,” Dr. Yuval Mika declared in a phone interview. “Basically what we are doing is we are changing the pressure in a way that the system will respond, the way that we want. I can tell you that we think we are not that smart. We don’t want to start to understand what the relationship is between the nerves’ activity and the pressure.”
It’s also not just a matter of changing how the heart functions. Sherman added that Backbeat’s algorithm can change the way the heart works, but given that the body can react to sudden changes in pressure, the system knows how to “trick” it.
“We do that by manipulating the algorithm so that we don’t always lower the blood pressure,” Sherman, who is also a BackBeat Medical director, said. “We lower the pressure for a lot of times and every once in a while let the pressure go back high.”
So how did the 35 patients whose results the company presented respond to the therapy? The study was structured such that patients would be implanted with the Moderato dual-chamber pacemaker but the therapy involving the algorithm wouldn’t be turned on immediately. This was done to ensure that patients on the pacemaker also demonstrated hypertension.
After the algorithm was activated, here’s what researchers found in the 27 patients that met all of the study inclusion criteria, according to a news release from BackBeat Medical.
- 24-hour ambulatory systolic pressure significantly decreased by 11 mmHg immediately after PHC activation and was maintained low during the study period.
- After three months, ambulatory pressure had decreased by 10 mmHg from pre-activation (p=0.004; 14 mmHg from baseline, p<0.001).
- Office cuff showed an average reduction of 16mmHg from pre-activation levels (p<0.001, 24 mmHg from baseline) after three months of therapy. The effect was maintained in patients who have so far reached later follow-up time points, with a significant reduction of 20 mmHg (p<0.001) from the pre-activation pressure after 12 months of therapy and 21 mmHg (p=0.02) after 24 months.
“This is a highly differentiated approach to treating hypertension that provides a significant reduction in blood pressure with relatively no additional risk because the pacemaker implants are already required for these patients,” said Dr. Petr Neuzil, one of the study’s investigators and the head of the department of cardiology at Na Homolce Hospital in Prague, Czech Republic, in a statement.
BackBeat Medical, whose name is inspired from a musical term and is a play on heartbeats, has already launched a second study, data from which will inform the design of the pivotal trial to win approval in the U.S. That trial won’t launch before early 2018, Mika said.
The goal for now is to win CE Mark — the process is already underway — and commercialize the Moderato device, with the proprietary algorithm. Ultimately, the software could be integrated on pacemakers already on the market and even be made available as a download in the way consumer electronics get a software refresh.
But of course getting device companies to add the algorithm function on their own pacemakers so that they too can address the 70 percent of pacemaker patients who are hypertensive will require formal business agreements.
BackBeat Medical has so far raised $15 million, Mika said, but executives declined to address how much needs to be raised to see the device through to the pivotal trial and commercialization in the U.S. and who the investors are.
The results from the small trial are heartening, but should the medical and investor communities once again get their collective hopes up on a device approach to managing high blood pressure given the failure of renal denervation and neuromodulation? As they say, fool me once, shame on you, fool me twice …
Sherman, who is also managing partner of Orchestra Medical Ventures (there’s that musical and medical connection again), according to his LinkedIn profile, believes so. Precisely because a successful device promises what drugs cannot: sustained compliance and lack of side effects.
“The concept (of renal denervation) was really worth it to get hyped about. I think where it feel short was that we didn’t look at the data with much scrutiny as we should have,” he said, noting that the therapy focused more on reducing the cuff pressure as opposed to the 24-hour ambulatory blood pressure. “When we did the (BackBeat Medical) study the patient was running as (his/her) own control. Each of our patients had a run where they got the pacemaker but the therapy wasn’t turned on. And then we turned on the therapy, and what you see is statistically different (results) both in ambulatory and cuff pressure measurements.”
Sherman is not aware of any other company which is looking at managing hypertension quite the same way. But to repeat a cliche, only time will tell whether BackBeat’s approach has merit and will be music to the ears of patients, investors and physicians.
