During the 1960s, professor Per-Ingvar Brånemark a discovery that would change healthcare worldwide – namely that titanium could grow together with skeletal tissue. Brånemark called this process osseointegration and its first area of use was in dentistry to anchor dental implants in the jaw.
Today, Mölndalsbolaget has Integral with the son and co-founder Rickard Branemark has taken osseointegration beyond dentistry and the process now forms an important part of the company's technology platform for developing innovative prostheses for amputees.
OPRA implant system
The basis of Integrum's operations is the proprietary OPRA Implant System which means that you can anchor a prosthesis directly to the skeleton. This avoids anchoring the prosthesis in a sleeve, as traditional prostheses do. By anchoring the prosthesis directly to the skeleton, you improve both the stability of the prosthesis and the patient's mobility. In addition, it is significantly more comfortable for the patient and leads to less pain and pressure.
The patient checks the prosthesis
Integrum's prosthetic system not only provides increased comfort and stability, but can also give the patient back the feeling of having control over their body. Traditional prostheses are often experienced as foreign and non-integrated additions that the patient cannot control. By using implanted electrodes, Integrum has developed a completely new category of prostheses that can communicate with the brain using artificial intelligence. The technology allows the patient to control the movements of the prosthesis neuromuscularly, but also gives the patient artificial sensation. This has been shown to have a major positive impact on the patients' mental well-being and quality of life.
Steady expansion towards important milestone
Since the first patient was operated on with an OPRA implant in 1990, more than 500 operations have been performed in 14 countries as Integrum has steadily advanced in the market. Much focus has been on the American market, the world's largest market for medtech products, where it has been active for almost a decade and has also had FDA approval for the past five years.
The FDA is currently processing an application from Integrum regarding so-called Pre-market ApprovalAn approval means taking a very big step forward in the important American market and would, among other things, make it easier to get Integrum's treatment approved by insurance companies for reimbursement, Reimbursement, which is an important piece of the puzzle for capturing market share in the US.
Three years ago, Integrum received its first order from the US Department of Defense and in 2018, it signed a framework agreement with the department worth SEK 60 million. It has also recently signed a cooperation agreement with the US Onkos SurgicalThe company, headed by Rickard Brånemark, also has research collaborations in place with well-reputed institutions such as MIT and Harvard Medical School as well as leading American hospitals such as Johns Hopkins and Walter Reed Army Medical Center.
BioStock had the opportunity to speak with Integrum's Chairman and Founder Rickard Brånemark about the company's technology, ongoing collaborations and the next steps in the company's development.
Rickard Brånemark, you are the Chairman of the Board of Integrum, a company you also founded with your father, Per-Ingvar Brånemark. Could you start by telling us a little bit about your professional background and how Integrum's journey began?
– I have a Master of Science in Engineering Physics from Chalmer and a licensed physician from University of Gothenburg with specialist expertise in orthopedics. My doctoral thesis mapped the biomechanical properties of osseointegrated implants, which among other things helped to redesign dental implants so that they would be strong enough to be walked on. In 1997, together with my orthopedic colleague, I wrote Magnus Ysander a major EU application. Unfortunately, we did not receive any EU funding at that time, but our work created the basis for the start of Integrum in 1998.
– Initially, I divided my time between Integrum and Sahlgrenska Hospital, until 2015. That year, Integrum received a special FDA approval, a so-called Humanitarian Device Exemption and I moved to San Francisco and got a professorship in orthopedics at University of California, San Francisco (UCSF) to help create a center of excellence there. Since 2019 I have been working part-time as a researcher at Center for Extreme Bionics, Biomechatronics Group, Massachusetts Institute of Technology (MIT), in Cambridge, Massachusetts, with a focus on developing new surgical principles to improve human-machine collaboration. In my case, the human is an amputee and the machine is a prosthesis attached with Integrum implants and using Integrum's control system (e-OPRA).
Integrum's technology has its roots in dentistry, stretching back to the 1960s. Can you briefly describe the development of your osseointegration technology, the process by which the skeleton fuses with titanium implants?
– The osseointegration part of Integrum’s technology platform was developed by my father in the 60s, and the first clinical application was dental implants. He discovered that titanium could grow together with skeletal tissue. In a very simplified way, you could say that Integrum’s OPRA implant system is a large dental implant, but the technology in its current form has been the result of many years of research and development.
The company's focus today is on improving the quality of life for amputees with bone-anchored prostheses. What advantages do Integrum's products offer compared to more traditional prostheses that are not anchored to the body?
– Given our background, the parallel to dental implants is obvious. Dental implants feel and function like your own teeth. False teeth are poorly attached and cause abrasions on the palate. Integrum's amputation implants attach the prosthesis to the skeleton, just like a real bone is attached. Traditional prostheses are attached with a sleeve on the outside of the bone and, just like false teeth, cause abrasions to the skin and are poorly attached or can even fall off.
– With our solution, you can sit and walk more as if you were not an amputee and we have several fantastic patient stories from people who have been helped – these can be found on our website. Among others from Erik Ax, who has had his implant for more than 20 years and also turns 80 in September!
Integrum is also a leader in a field that to the uninitiated almost borders on science fiction, namely prostheses that can be controlled neuromuscularly by the wearer. Can you tell us a little about this groundbreaking technology and how it can impact patients?
– Anchoring an amputation prosthesis to the body in the best way leads to decisive improvements compared to traditional technology. For the prosthesis to be more like a real leg or a real hand, even more is required. The prosthesis must be able to “talk” to the brain in a way that is easy for the brain, just like when you wave your hand. This can be done without any noticeable mental effort, you do it naturally.
– So how can the prosthesis talk to the brain in a natural way? We decided to use implanted electrodes that sense muscle movements and that can send signals to nerves to create artificial sensation. The OPRA implant that we have already used for many years has a through hole that is closed with a small screw. We converted this small screw into a smart screw with 16 very thin wires that are connected to muscles and nerves inside the body and on the outside to the Integrum electronics unit. This electronics unit can, with the help of artificial intelligence, talk to the brain in a natural way.
»In our main market, the USA, Integrum is the only company with an FDA-approved product.« – Rickard Brånemark, Chairman and Co-Founder, Integrum
Back in 2013, a Swedish woman made history as the first patient ever to receive a prosthesis that both gives the patient sensation and can be controlled via neuro-muscular impulses - how has that affected interest in Integrum, not least internationally?
– Integrum is leading this development and we are many years ahead of our competitors. There is currently no competitor that has a system that can be used outside the laboratory, but Integrum has had it in place since 2013. This is a very advanced system in a very resource-intensive area, but despite this, it is a small Swedish company that is leading this development.
– There is interest from American Department of Defense for a long time. Integrum has of course been keen that this interest should lead to a concrete collaboration and we have also had a commercial agreement in place since 2018. Our continued collaboration with Chalmers and Sahlgrenska Hospital, as well as with MIT and Harvard Medical School in the USA, will continue to strengthen our position.
What does the global competitive landscape look like in your area of operation and how well is Integrum positioned relative to its competitors?
– In our main market, the USA, Integrum is the only company with an FDA-approved product. In other markets, there are a smaller number of commercially active competitors, but so far neither of the two major orthopedic companies has begun development of competing implant systems, Zimmer/Biomet and DJO Global, have managed to push their development projects to the commercial phase. Both of these companies have the US as their primary market and Integrum's assessment is that they will not be able to produce an FDA-approved product for at least the next three years.
Integrum's main markets today are the US, Australia and Europe. How large do you estimate the potential market for your products to be in a global perspective?
– Integrum's main product OPRA Implant System for femur amputees has relatively narrow indications, but even with only these indications, the potential US market is valued at more than SEK 10 billion.
The company has been active in the US market for several years and, as you mentioned, in 2018 you signed a framework agreement with the US Department of Defense (DoD) worth the equivalent of SEK 60 million. Can you tell us a little about how the collaboration has developed since then and what you hope it can lead to?
– We have an excellent collaboration and DoD is very satisfied with both the product and the company. Currently, two studies are underway with DoD, one for femur amputees and one for upper arm amputees, both with OPRA. We expect that the collaboration will continue and that there are very good conditions for an in-depth collaboration, especially considering the great interest in e-OPRA.
In addition to the collaboration with the US military, Integrum also has a collaboration with an American company called Onkos Surgical, which specializes in the field of cancer surgery. What can you tell us about your partnership?
– Onkos is a relatively new orthopedic company that has been around since 2015, focusing on advanced orthopedic implants that are often used in tumor surgeries. The company is led by a group of highly experienced former employees from Stryker which is one of the world's largest orthopedic companies. They have solid expertise in selling advanced orthopedic products to leading hospitals in the US, which is largely the same target group that Integrum is targeting. We have high hopes that the collaboration with Onkos will lead to significantly faster growth in the US.
»The more leading hospitals in the US, such as Johns Hopkins, that start using Integrum's products, the more other hospitals will become interested – and not just in the US.« – Rickard Brånemark
Does the company have any similar collaborations in other markets?
– We are still in an early phase in the collaboration with Onkos and we need to evaluate it further, but the experiences we have seen so far indicate that this is a collaboration model that we will also evaluate in other markets.
Given that you have developed a world-leading technology with the potential to change patients' quality of life in a strongly positive direction - what do you see as the most important thresholds for Integrum to pass in order to achieve a real breakthrough in terms of sales?
– I strongly believe in both a successful collaboration with Onkos and an even clearer sales focus in EMEA. The more leading hospitals in the US, such as Johns Hopkins, that start using Integrum's products, the more other hospitals will become interested – and not just in the US.
To what extent have your expansion plans been affected by the ongoing corona pandemic?
– All planned healthcare has of course been put on hold during the pandemic. In the short term, this has a negative impact on our revenues, but in the long term, the patients remain and the interest in our solution remains.
An important milestone that could be of great importance to the company's continued expansion plans in the US is the possible approval of the PMA application that was submitted almost a year and a half ago. What can you say about your expectations for it?
– We have of course submitted the application with the aim of it being approved. However, it is the FDA that handles the approval process and we expect this decision to come during the year. A positive decision is not only an important seal of quality for Integrum but also a door opener for faster expansion in the USA. It will be easier to get the treatment approved by more insurance companies and Integrum can more easily create the basis for an approval of Medicare which is the insurance system for retirees in the United States, which can be a time-consuming process.
Finally, in addition to the PMA application, what other milestones can we expect from Integrum in the coming year?
– In the US, the focus, in addition to the PMA application, is primarily on developing the collaboration with Onkos. We have also just completed the recruitment of a very experienced marketing and sales manager for EMEA who will not only strengthen our market penetration outside the US, but also implement an improved training package primarily for surgeons, so that the company becomes less dependent on my participation and gives us the opportunity to quickly train more surgeons, which will be of great importance for our upcoming scale-up of the business.