In high risk patient populations, spinal fusion surgeries can fail as often as 40% of the time, a massive problem costing the U.S. healthcare industry $80B each year.

Bioverge is excited to share with you Intelligent Implants, a medical device company focused on drastically improving the speed, safety, and success rate of spine surgery. 

The company is led by a world-class team highly specialized in medical device development and, specifically, electrical stimulation. Prior to founding the company, the team had been concentrated on the development of cutting edge approaches to neural stimulation. However, a family member's orthopedic issue turned their attention to this underserved issue and untapped market opportunity. In addition to the size of the problem, the team was particularly struck by the lack of fresh technology approaches that had been tried to solve it, with the most recent advance having been launched as far back as 1996.

It was through this lens that led them to imagine incorporating state of the art electronics into conventional spinal implants, enabling a potent combination of electrical stimulation for enhanced bone growth, real-time stimulation control and growth monitoring, as well as wireless power and data transfer.

They went on to develop SmartFuse, a wirelessly powered spinal implant that utilizes electrical stimulation to safely and yet rapidly enhance bone healing (2X faster) and reduce the rate of failed bone fusions (4X improvement). With SmartFuse, Intelligent Implants is striving to reach 100% fusion rates following orthopedic surgery, helping patients to recover faster, avoid major complications, and do so without adding complexity or additional safety risk to the surgery.

While the use of electrical stimulation for enhancing bone growth has been supported by the research literature for ages, the technology underlying the SmartFuse has only just reached the point of commercial feasibility and clinical viability. It’s hard to imagine a team better suited to make this a reality than Intelligent Implants. 

Opportunity Highlights

-- Intelligent Implants is incorporating wireless implantable bioelectronics into the form factor of standard orthopedic implants in order to stimulate, modulate and monitor bone growth in real-time

-- For high-risk patients, such as those afflicted by obesity, diabetes, a history of smoking, or osteoporosis – a majority of patients - this is a major challenge. In standard spinal fusion surgeries, for example, the rate of successful fusion is as low as 60%,  with each corrective procedure costing the healthcare system $120K, in addition to the pain and reduced quality of life for the misfortunate patient

-- With the SmartFuse system, Intelligent Implants is striving to reach 100% fusion rates following orthopedic surgery, helping patients to recover faster, avoid major complications, and do so without adding complexity or patient safety risk to the surgery

-- SmartFuse Advantages: proven science, enhanced bone growth (speed and density) and superior fusion rates without the safety risks associated with current approaches, directed and localized stimulation, sensors for real-time tracking of bone growth and fusion progress, on-demand stimulation adjustments to optimize for each patient, standard implant size and shape, no change to surgical procedure, wirelessly powered, connected device delivering real-time data for remote tracking of patient compliance and for decision support, eliminated need for ongoing CT and X-Ray scanning, no additional patient safety risk, improved patient experience, reduced recovery time for patient, patient back to daily activity and work faster 

-- Extensive supporting literature, predicate devices, and recent SmartFuse large animal studies support the potential for significant enhancements to bone growth and reductions in failure rates using electrical stimulation

-- Initial focus on the $4.5B interbody spinal fusion market, characterized by 650k patients per year and a 20% failure rate, which is devastating for patients and costs the healthcare system $80B annually

-- Progress: successfully validated superior bone growth in  small and large animal studies, now finalizing large animal testing in preparation for FDA submission; finalized electronics and prototyped form factor of human implant, now finalizing algorithm and user interface for real-time modulation of stimulation and tracking of bone growth

-- Following comprehensive due diligence and IP review, J&J invited Intelligent Implants to be the first resident company in the newly formed  J&J Center for Device Innovation, signifying strong strategic alignment with the medical device and orthopedics giant.

-- IP: 6 international patents pending; positive feedback from global review of patent literature by World Patent Organization

-- Regulatory: positive feedback and enthusiasm from FDA in initial discussions; potential for streamlined regulatory pathway due to limited patient safety risk profile, enhanced bone growth, and existence of historical electrical stimulation devices and associated safety/efficacy data

Dive Deeper

The Problem:

Spinal fusion is a surgical procedure where one or more of the spine’s vertebrae are purposely fused together so that no motion occurs between them. The goal of the procedure is to restore stability to a damaged spine. It’s an operation that is called upon for the treatment of a number of spine conditions including degenerative diseases, tumors, and traumas. 

Video: Spinal Injury Animation (via Handyside; ~2mins)

About 1.4M spinal fusion surgeries are performed each year globally, with ~50% of these taking place in the U.S and ~20% in Europe.

To accomplish such a lasting bond between bone, one that can permanently support the everyday stress experienced by the human spine, surgeons do what they can to induce bone growth in the space between the bones they are trying to connect.

Video: Overview of Spinal Fusion Surgery (via Manipal Hospitals ; ~4:30mins)

Perhaps not surprisingly, the biggest problem in spinal fusion surgery is the high rate of failure. A failure is when the patient’s spinal bones fail to form a stable and permanent union. For a random sampling of patients, the failure rate for spinal fusions is estimated to be ~20% on average. That is, 1 in 5 spinal fusions attempts will fail on average. At a procedure cost of $120K, this is a very big problem by itself. But it doesn’t stop there…

For at-risk patients, such as those afflicted by obesity, diabetes, a history of smoking, or osteoporosis – nearly half of all patients, the failure rate can jump up to 40%!

The Patient Perspective

And while the healthcare system is struggling with the financial repercussions of this problem, it’s the patients and their loved ones that have it the worst. 

A spinal fusion failure can take 18 months or more from the initial surgery to diagnose. During this time, the patient remains in pain and there is a high risk permanent nerve tissue damage. Often pain medication is needed to get by. Since fusion failure can be difficult to asses using X-rays alone, the diagnosis is often very challenging and highly subjective. 

Spinal fusion revision surgery has even worse prognosis when it comes to both fusion success rates and guaranteeing a reduction in pain. Following the initial surgery, patients and their families are left to deal with the physical and emotional toll of the failed procedure, which means, at the least, a continuation of existing pain, if not the introduction of new pain, a delayed return to mobility, independence, and/or work, and an ever-increasing medical bill. 

In a patient’s own words: 

“So, I've failed. Surgeon isn't calling it that yet because hardware is still in place. But i have had literally no bone growth and im 5 months post op. My pain is exactly the same...horrendous. Shoot...i was WAY better off my first time around, i was running 5ks then. Right now  at work or in bed on ice and bawling and screaming. I'm back to work because I'm about to lose my house to foreclosure and everything else. This has completely ruined my life. Id take my own life if not for my kids. I can not live like this. And i don't know what the next steps are. What do u think? More cutting? Do they wait for me to break this hardware? Living hell.”

It is not uncommon for the pain and associated complications following a failed spinal fusion to be worse than they were prior to the surgery. 

A Patient Story: “If I knew then what I know now, would I…” (Kerry Smith; ~1min read)

So, Why is This Happening?

Growing bone in the spine is complicated by two unique technical challenges. The first is that spinal vertebrae are not meant to grow together. In a healthy individual, these bones are naturally separated by a soft discs that serve as spring-like shock absorbers and allow the bones to move/bend largely independent of each other. 

Video: Movement of the Spine (via Animated Biomedical; ~30secs)

Rigidly fusing the bones together defeats the purpose of this natural flexibility and, as a result of this superficial restriction, typical spinal movement by the patient (twisting/bending/etc) ends up applying a great amount of pressure on the newly-fused spine. And in the case of spinal fusion failures, sometimes the surgical union is unable to handle the pressure and breaks down, requiring that the patient undergo another surgery or explore alternative options.

What is currently being done to address it?

The spinal implant industry has long been frustrated by this issue and has continually sought ways to induce bone growth between spinal vertebrae that is sufficient to fuse them together into a rigid and lasting unit.

In attempt to increase fusion rates, some spinal surgeons add additional biological compounds to the surgical fusion site that are known to enhance bone growth. The most prevalent, and current industry gold standard for at-risk patients, is called BMP-2 (bone morphogenetic protein 2).

The problem with BMP-2 is that it is really good at growing bone. So much so that its effect can be very difficult to control, which is especially dangerous in areas of the spine, where the spinal cord and spinal nerves are housed. BMP-2 has been demonstrated to promote excessive growth outside of the surgical site that can result in patient pain, disabilities, including paralysis in severe cases, and has been linked to cancer. BMP-2 is currently sold by Medtronic under the product name Infuse, however, the company has been under fire in recent years due to published studies reporting “frequent and occasionally catastrophic complications associated with use of BMP-2 in spinal fusion surgeries", with a level of risk far in excess of estimates reported in earlier studies.

Table: Side Effects Associated with Medtronic Infuse Bone Grafts (BMP-2)

Article: A Closer Look at Ectopic Bone Formation and the Medtronic Controversy (via VeryWell Health; ~1mins)

Not surprisingly Infuse utilization and sales figures have drastically subsided in recent years as follow-on reviews have continued to shed light on BMP-2 associated complications. Spurred by this data and the underlying Infuse controversy, the industry is actively searching for new approaches/new biomaterials that, critically, are able to grow bone efficiently and also with great caution and control.

Solution & Grand Vision

Looking across the major fields of surgery, such as neuro and cardiovascular, you will see that, on the whole, each has over time widely and deeply explored electrical, mechanical, and biological approaches to therapy, as well as a hybrid combinations of each.

However, if were were to zoom out and generalize, innovation in the orthopedics space has traditionally focused heavily on the mechanical side of engineering. As in, ‘how can we develop implants to more closely mimic the versatility, stability, and mechanics of the spine?’. From there, we often combine these advances with the use of a limited set of biological compounds, such as BMP-2, to promote bone growth and enhance surgical results. And yet, despite safety and efficacy issues with BMP-2 and the disturbingly high failure rate of fusions, the field has not deeply explored innovation on the electrical side of the equation.

This is truly interesting because electrical stimulation is far from a new kid on the block. There exists an extensive body of literature to support the capabilities and advantages of using electrical stimulation to enhance bone growth and healing. 

So, why hasn’t this been tried in the spine? Turns out, even that has been attempted. In fact, it is so well established that there exist clinical studies demonstrating the ability of electrical stimulation to decrease spinal fusion failure rates by between 55-75% compared to control groups, effectively raising the procedure success rate to ~95%. And even better, this approach and the associated results can be highly controlled and are free from the complications associated with biologics, such as BMP-2. 

Why isn’t this already used widely? The reason that electrical stimulation has been largely shelved by the orthopedics world to this point is that, in order for the benefits of electrical stimulation to be maximized, there needs to be a method to deliver electrical stimulation directly to the site of bone fusion. Stimulating from a distance, whether outside the body or from nearby tissue has the potential to be beneficial, but is neither potent nor targeted enough to promote faster and targeted bone growth.

This subtle aversion to electrical-based innovation is incredibly apparent when you look at the 4 available electrical stimulation technologies that are currently available on the orthopedics market today. Among them, 3 were released in the 1980s, and the fourth, in the early 1990s - making them ridiculously dated when it comes to the unrelenting pace of cutting edge technology innovation.

If that weren’t telling enough, a closer examination makes clear why these technologies are inadequate for the task at hand. The first 3 are external stimulation systems - due to their literal separation from the fusion site, these are dramatically less targeted and subsequently less effective at aiding bone fusion. For these reasons, independent clinical trials have demonstrated only a minuscule 2% increase in fusion rates using external stimulation systems.

The other is an implantable stimulator called the SpF and sold by Zimmer-Biomet. Despite its age, this device actually offers key support for the use implanted electrical stimulation to promote enhanced bone growth.

In several major clinical studies, the Zimmer-Biomet device has demonstrated the ability to significantly improve fusion rates. Unfortunately, the device was designed with a number of flaws that hindered its commercial success. For example, the device’s power source is a battery pack that is implanted along with the electrodes into the patient. As a result, the battery pack needs to be removed in a separate surgery 3 months after the initial operation, an additional time/resource expense and inconvenience for the patient, hospital, and surgeon. Additionally, Surgeons wishing to use the the device are required to complete extensive training, a roadblock to wide adoption. Another major challenge to adoption was that the device was developed for a surgical procedure that is very invasive and, as such, is now considered outdated and not often used today.  

Table: Current State of the Spinal Fusion Implant Market   

To recap, clinicians and the medical industry have been attempting to solve the problem of spinal fusion for decades. Existing solutions are either not doing their job, are putting patients at risk, or were developed based on technologies and techniques developed in the 1980s and early 1990s. Despite electrical stimulation being the most efficient and safest way to aid fusion following spinal fusion surgery, no device is currently available to surgeons that leverages the full spectrum of advantages of the technique in a clinical environment. When the Intelligent Implants team caught wind of this issue, they immediately sensed an opportunity...

The Underlying Insight

Enter the Intelligent Implant team, whose personal connection to the problem and highly specialized background make them ideally suited to think outside the traditional orthopedics box and successfully disrupt this space. 

In 2014, company co-founders Dr. Erik Zellmer (CTO; PhD Biomedical Engineering) and Dr. Rory Murphy (CMO; Surgeon) were collaborating on a number of projects pertaining to nerve stimulation. During this period, they spent extended time in the surgery suite, identifying clinical needs for their research projects. Many of the surgeries that they observed together were spinal surgeries. It became increasingly evident that many patients were in the hospital for revision surgeries due to failed spinal fusions, an issue close to Dr. Zellmer’s heart.

This isn't just business, it's personal

Over the past 20 years, the mother of Dr. Zellmer and his brother John Zellmer (CEO) has undergone several spinal fusion surgeries. Following her first surgery, the vertebrates failed to fuse together, which meant that a revision surgery was needed. Following the second surgery, Mrs. Zellmer was subject to bone overgrowth that was particularly dangerous as the newly formed bone was growing into her spinal nerves. Yet another revision surgery was necessary to clear out the excessive bone growth. While she has since been able to avoid the operating room, we are sad to report that she has been on strong pain medication and only able to work part time for more than a decade.

Upon researching the problem in further detail and reviewing the standard of care, Dr. Zellmer and Dr. Murphy were shocked to learn that aiding bone growth and preventing failed fusions was a massive unmet clinical need and that the multibillion dollar orthopedic implant market was lacking in disruptive innovation.

Dr. Zellmer knew that electrical stimulation had been well established as an effective way to stimulate bone growth, and went on to suggest that they attempt to incorporate an electrical stimulation system into the standard cage implant already used during spinal fusion surgeries. Further, the electronics could also monitor bone growth in real-time as a way to both optimize stimulation type and prevent adverse effects. With this approach, there was potential to simultaneously aid bone growth, avoid failed unions, and improve patient safety. 

A Seamless Fit

Even more exciting, the focus of Dr. Zellmer’s research up to this point in time had centered on cutting edge approaches to electrically stimulating human nerves. His proposal for the novel spinal implant implied that they could adapt the same state-of-the-art wireless, implantable stimulation systems that he had been pioneering for stimulating nerves, except apply them to the orthopedics space. 

Intelligent Implants was incorporated shortly thereafter. The combined experience of Dr. Zellmer (Chief Technical Officer), Dr. Murphy (Chief Medical Officer), and Dr. Juan Pardo (Principal Engineer) make this team uniquely suited to tackle this problem. In fact, it’s hard to imagine a better fit.

Introducing SmartFuse

SmartFuse brings together the best of both worlds, combining electrical stimulation and real-time monitoring with the standardized shape and capabilities of a traditional spinal implant. By incorporating state-of-the-art bioelectronics into the implant, SmartFuse is able to overcome the many challenges associated with spinal fusion alternatives and deliver a more effective, precise, and safe result for patients.

Features:

With SmartFuse, the company is the first to bring electrical stimulation to the site of bone fusion. This alone is a revolutionary approach that will enhance bone growth. However, SmartFuse takes things several steps further, placing three new capabilities into the hands of orthopedic surgeons that were not possible before.

-- Sculpting Bone Growth. Using SmartFuse, orthopedic surgeons will, for the first time, actually be able to sculpt bone growth. This is because the Intelligent Implants team has designed SmartFuse such that each of its electrodes can be controlled individually. This is a major features as it enables the surgeon to finely tune the end result. 

As an example, a surgeon that is seeking to enhance bone growth in a specific region, would set the nearest electrodes to carry a negative charge. This has the known effect of growing bone around the electrode. If the surgeon was concerned about excessive bone growth nearing surrounding soft tissue, they might set the nearest electrodes to carry a positive charge, which would inhibit bone growth in that area. A third setting, neutral, could also be used in areas that were at low risk of safety or fusion failure. The ability to use combinations of these settings and means that surgeons will now be able to precisely and efficiently grow bone where it is needed and inhibit growth in areas where there is a safety risk, allowing treatments to be calibrated to each individual patient.

-- Monitoring Bone Formation. Enhancing and shaping bone growth is an important piece to the puzzle, however, as evidenced by the high failure rate and complications associated with BMP-2, being able to closely monitor bone growth, or the lack thereof, over time is critical. SmartFuse utilizes what is called electrical impedance tomography (EIT) to allow the system to sense bone growth in real-time. This a revolutionary advance because it enables bone growth to be quantified regularly. This key piece of information allows the surgeon to keep a close eye on whether the patient is fusing correctly and can do so without the time, equipment requirements, and cost associated with regular X-Ray and CT scans.

-- Optimizing Results in Real-time. With the SmartFuse system, surgeons can remotely sculpt and monitor bone growth, sure, but what if they want to make a change along the way? SmartFuse makes this possible.

This is perhaps the most important feature of the SmartFuse system. With it, surgeons can calibrate treatment for each patient, closely monitor progress, and ultimately adjust the treatment in real-time to improve results. If bone growth appears to be threatening nearby soft tissue, surgeons can tweak settings to either prevent further growth in a that specific area or even reverse it. If the treatment “dose” of stimulation isn’t resulting in the bone growth necessary for permanent fusion, surgeons can adjust the intensity and pattern of stimulation to enhance results. And if SmartFuse monitoring confirms that a fusion is ahead of schedule or complete, surgeons can advise a patient to modify their physical therapy plan as a result. Together, these three features mean that the SmartFuse, which has the outer appearance of a conventional spinal implant, a form that surgeons are familiar with, is actually the most capable spinal implant on the market, enabling for patients and surgeons a faster, more reliable, and safer spinal fusion.

SmartFuse is cloud connected for data storage, powered wirelessly by an external power supply, and can be controlled in real-time through an external interface (e.g. smartphone, tablet). In the event that physicians would like to deactivate the device for any reason, the system can be turned off either by using the external device settings or simply by removing the device’s external power source. Importantly, a SmartFuse system that is turned off remains 100% structurally effective to the patient as a standard spinal implant.

Future Plans: 

Intelligent Implants is confident that the underlying technology behind SmartFuse can be readily repurposed for more quickly and effectively healing bone in other regions of the body, such as cranial and long bone fractures and strengthening the bone surrounding hip implants.

The team also sees an opportunity to mine its trove of patient bone growth data to build a predictive model capable of determining whether a patient is a good candidate for surgery, and if so, when a patient is expected to be fully healed if all goes according to plan.

IP:

Intelligent Implants has a robust intellectual property position with 6 international patents pending that have each been comprehensively reviewed for patentability and freedom to operate.

Exit Opportunities:

Intelligent Implants have a plan and the ambition to exit this company within 3 years following the completion of the company's human clinical studies. The company has identified 5 large medical device companies that would be a strong potential fits for the technology: J&J, Medtronic, Stryker, Nuvasive, and Zimmer-Biomet. 

The Road Ahead

Development status: 

-- Intelligent Implant has completed 20 large animal case studies that have demonstrated their technology’s ability to accelerate spinal fusion healing time. They plan 20 additional case studies throughout 2019 before transitioning their focus to human trials.

-- In 2018, Intelligent Implants signed a collaboration agreement with J&J, following an extensive due diligence review on the company’s team, technology, and IP. J&J was impressed and subsequently offered Intelligent Implants to be the first resident in its newly formed Center for Device Innovation (Houston, TX), reserved for companies that are strategically aligned with J&J. As part of this collaboration, Intelligent Implants has access to J&J's network of expertise device development resources, including extensive support from J&J's Orthopedic division. In exchange J&J has a right of first negotiation during the term of the contract.

Next Steps:

Intelligent Implants is on track to move to human trials of the SmartFuse system in early 2020. Preliminary discussions with the FDA have been extremely positive. To bolster its application, the company will pursue regulatory approval and launch in Europe prior to formally seeking approval with the FDA, a more rigorous pathway. Intelligent Implants is laying the groundwork for a 15-patient validation study to demonstrate safety and superior fusion rates and amongst high-risk patients treated using the device.

In parallel,  the company is taking necessary steps to refine the SmartFuse device and software for commercial production, including optimizations for manufacturing, packaging, and distribution and has partnered with Sanmina, an trusted expert in the space.

Another Layer Deep

-- Supporting Literature

-- Published Patent Applications (pending)

-- Company Press