Many doctors and most patients have probably never heard of focused ultrasound, but the pace of research, clinical trials and device manufacturers dedicated to the emerging technology could very well give it a solid place in mainstream medicine soon.

“The dialogue has shifted this year from if to when,” says Dr. Neal Kassell, chairman of the Focused Ultrasound Foundation. “What remains to be sorted out is the indications where focused ultrasound can provide solutions that fulfill unmet clinical needs.”

Treating uterine fibroids is one application where the technology has been most successful.

In the U.S., it’s the only indication approved for FUS. The Israeli company InSightec Ltd. received U.S. Food and Drug Administration clearance in 2004 for its MR-guided FUS system to treat women with uterine fibroids, followed by a second indication for pain relief from bone metastases. According to Lynn Golumbic, the company’s director of marketing, ten thousand women have been treated using the technology so far.

Philips Healthcare also has an MR-guided FUS system but it’s only approved in Europe, Canada and Korea to treat uterine fibroids, with FDA clearance pending.

FUS focuses high intensity ultrasound waves to a target deep within the body. But it can only work with the help of MRI guidance, and regular ultrasound in some cases, to precisely see the target and monitor the heat being generated. One company, HistoSonics, has even developed an off-shoot HIFU treatment called histotripsy. Whereas HIFU applies focused sound until the targeted tissue is destroyed by heat, this technique uses much shorter, higher-amplitude pulses, which are powerful enough to destroy the tissue without heat. It’s tracked with ultrasound imaging.

FUS treatment of uterine fibroids heats the fibroid to about 65 degrees centigrade —enough to ablate the tissue without putting the patient at too much risk.

“With MRI, we see temperature coming up and you can intervene in time to not do permanent damage,” says Thomas Andreae with Philips’ MRC Therapy Business Development unit.

He points out that Philips’ technology, the Sonalleve, is volumetric heating with real-time feedback allowing the clinician to focus rapidly on larger areas thereby treating fibroids more efficiently. MR-guided FUS treatment for fibroids takes about three hours to treat and can be an alternative to a hysterectomy — which is a more risky surgery that involves removal of the whole uterus along with an extended recovery period.

“The main advantage and value proposition [of FUS for uterine fibroids] for the patient is that you have a non-invasive treatment that is outpatient and recovery is a day or two,” says Andreae.

Plus with FUS treatment for uterine fibroids, women still have a chance of having kids —something that is not typically possible with a hysterectomy.

“We see a clear demand from women for a uterus sparing procedure,” says Andreae. “Especially as women have children later and the chance of uterine fibroids increases in your thirties.”

Kassell believes FUS for the treatment of fibroids highlights why the timing is just right for the technology to take off in the U.S., where health care reform is rewarding a system centered on cutting costs and rewarding more outpatient procedures.

But commercial success in the U.S. of FUS to treat uterine fibroids depends largely on reimbursement — currently of which there is none.

On the road to reimbursement
Reimbursement has been one of the biggest challenges for FUS adoption in the U.S., according to Susan Klees, communications director at the Focused Ultrasound Foundation.

“If it doesn’t have widespread reimbursement, then adoption is going to be slow because people won’t want to invest in the technology,” she says. Even so, some patients who have been treated with FUS have been able to successfully work with their payors to be reimbursed for it.

Although FUS treatment for uterine fibroids is currently not reimbursed in the U.S., there are many efforts in the works to try and change that.

Philips is still running its phase 3 randomized control trial — SOPHIA — to help gather objective data that will be used to help gain reimbursement for the treatment of uterine fibroids with FUS. In addition, InSightec and Philips, along with the Focused Ultrasound Foundation, have initiated a global registry, called RELIEF, to record both the clinical outcomes and economic data over a three-year period on FUS for the treatment of uterine fibroids. The idea is to treat 1,000 patients over a two-year period and then spend a year following up to get the clinical data, says Philips’ Andreae.

It’s a no-brainer that HIFU’s success hinges greatly on the results of clinical trials going on now, as well as others that are planned for the near future.

In the works
FUS isn’t all that new. Lars Leksell helped develop the technology in the 1950s to treat functional brain disorders, but eventually abandoned the idea because it was hard to pinpoint the affected areas of the brain through the skull without advanced imaging, like MRI, which is key because the clinician needs to be able to image and test the target as well as measure the temperature during treatment. Leksell instead went on to invent the gamma knife in the late 1960s.

Around the globe, there are nearly two dozen companies invested in developing FUS technology. In the U.S., all of these companies rely on MR scanners to guide therapy, but in other countries, ultrasound imaging is sometimes used to guide the treatment. In a typical scenario, a patient lies in an MRI with a transducer attached to the area being treated. The MRI scan is paired with the ultrasound images. Some researchers, working with companies like SonaCare Medical and Philips, are trying to make that real-time image acquisition process less tedious through fusion algorithms.

Besides success to treat uterine fibroids, InSightec is in a position to see its system, the ExAblate Neuro, commercially available in the U.S. to treat patients with essential tremor, a neurological disease characterized by shaky hands and limbs that affects roughly 10 million Americans.

In August, 2013, the Phase III study for the device began that will evaluate a large cohort of patients in eight sites around the world. Radiation treatment and surgery can currently treat essential tremor, but these options have drawbacks for many patients. Medication is also available, but drugs can vary in effectiveness with many patients not responding to them. Golumbic says InSightec’s technology is not meant to compete with drugs and instead can be looked at as another option for these patients — often referred to as “medication refractory” — who don’t want to undergo surgery or radiation therapy.

While the gamma knife is able to treat essential tremor noninvasively using the same target as the ExAblate would, some patients are reluctant to go through with radiation treatment because it can take up to three months before results appear. Another treatment option available for patients is something called deep brain stimulation. However, it’s an invasive procedure where a pacemaker-type device is surgically implanted into the base of the patient’s neck to control tremors. Most cases also require the patient to be awake for part of the procedure.

According to Golumbic, ExAblate has treated roughly 50 patients so far for essential tremor.

Although final results of the ExAblate Phase III trial won’t be available for about two years, the technology’s success with essential tremor could pave the way for other treatment applications, like Parkinson’s disease, epilepsy and even OCD and depression. InSightec has just begun a trial for ExAblate on Parkinson’s disease patients and they also have an early stage trial underway in Korea to treat OCD.

Prostate space
One application where FUS is used frequently — and often using ultrasound guidance — is outside of the U.S. for the treatment of prostate cancer.

According to John Rewcastle, medical director for the French company EDAP, over 40 thousand high intensity focused ultrasound procedures for prostate cancer have been performed in Europe. (Some patients get more than one treatment so quoting procedures is more accurate).

“Fifteen years ago treatment would have been aggressive with a cure at all costs mentality. Now it’s more of a balance of treatment effectiveness with the side effects of the treatment and that’s where we fit in,” says Rewcastle.

In more recent years, evidence has surfaced discouraging aggressive therapy to treat prostate cancer due to the risk of side effects outweighing any benefit of treatment.

In February 2013, EDAP submitted a premarket approval application to the FDA to gain clearance of its Ablatherm-HIFU for treatment of low risk, localized prostate cancer.

The Canadian-based company Profound Medical announced that they are weeks away from enrolling patients in a multijurisdictional clinical trial taking place in the U.S. and Europe for its MR-guided therapy for prostate cancer. Profound’s probe is unique in that it heats the prostate from inside to its boundary on the outside, as opposed to a trans-rectal application.

“Current techniques use a probe inserted into the rectum and heat across the rectal wall into the prostate and across the urethra into the other side,” says Steven Plymale, CEO of Profound. “Anatomically, we feel we have the advantage where we can more effectively reach our target a lot faster.”

The OR of the future?
While some FUS technology could be used in the urologist’s office — a shrink-wrapped ultrasound-guided version of the technology to treat prostate cancer for example — all experts interviewed for this story agreed that any MR-guided system should be portable with the ability to be used by many specialists in a health care setting.

InSightec envisions it as the “OR of the future,” and a strong competitor to traditional surgery.

“One big problem we face with all treatment is the cost of hospitalization. With this [technology] and prostate cancer for example, the procedure can be short, the patient goes to recovery room few hours and then goes home,” says Dr. Mark Schoenberg, chief medical officer at SonaCare Medical. He says he believes that technologies that will offer appropriately selected patients the opportunity to manage a cancer diagnosis with minimal collateral morbidity

DOTmed Registered DMBN 2014 Therapeutic Ultrasound Companies

Names in boldface are Premium Listings.
Domestic
Eddie Bright, Fitco Medical, TX
Dawn Byrd, SonaCare Medical, GA

International
Gil Gefen, InSightec, Israel