Jeffrey G. Marx, Ph.D., and Glen Kashuba are two orthopedic device executives well-versed in the art of patience. Dr. Marx serves as the President and COO and Kashuba’s role is CEO at Cerapedics, an orthopedic device company that offers the peptide-enhanced bone autograft replacement product i-FACTOR. By Dr. Marx’s estimation, it took 12 years between the development of Cerapedic’s i-FACTOR bone graft product and commercialization in the U.S., which came after achieving FDA’s Premarket Approval (PMA) for cervical spine surgery in late 2015. With Kashuba and Dr. Marx joining Cerapedics in 2013, they weren’t with the company during the early days of i-FACTOR’s development, but heading a company whose only product took more than a decade to commercialize seems to have imparted a philosophy focused on waiting to bring something truly new, safe and effective to the bloated orthopedic market to differentiate.
“I’m a firm believer that there are no shortcuts in business or life,” said Kashuba, the former President of Biomet’s Spine & Bone Healing Technologies. “With Class II device clearances, there’s an incremental tweaking of many products that flood the market and cause pricing issues and a lack of differentiation. If you want to develop an innovative product, you can’t be worried about putting the time and money behind data and clinical studies.”
The chief reason i-FACTOR took so long to be commercially available in the U.S. is something both Kashuba and Dr. Marx now sell as one of its greatest assets. Instead of being one of myriad Class II bone graft devices that pass FDA clearance quickly and easily by making small adjustments to otherwise nearly identical products, Cerapedics is one of only two companies with FDA Class III bone graft technology on the market for use in the spine. Accomplishing this took years of stringent human clinical trials and a significant financial investment. (Wright Medical's AUGMENT® is also a PMA/Class III bone grafting product, though for a different indication: ankle and hindfoot arthrodesis.)
“The challenge with a Class III device is that it takes both an IDE [investigational device exemption] and PMA, and that can take companies upwards of $20 million and four to five years to complete,” Kashuba said. From his perspective, Cerapedics’ Class III status delivers the sort of trust and legitimacy that nearly all of their competitors can’t match. “It means we’ve proven prospectively with level 1 data that our product is safe and effective. We’re able to leverage that in the marketplace.”
“There are over 400 approved bone graft material products being promoted for use in the U.S.,” Dr. Marx said. “Only two have gone through the full IDE PMA process with prospective, randomized human critical trials to show that they’re autograft replacements and not autograft extenders. That’s us and Infuse.”
Kashuba remarked that Cerapedics’ flagship product has distinct advantages over Medtronic’s Infuse in terms of safety, its ability to grow bone “more uniformly,” and cost effectiveness.
Autografting bone is the process of harvesting bony material from one part of a patient’s body and using it to repair and regenerate bone in another. To illustrate the differences between autograft replacements like i-FACTOR and autograft extenders such as the vast majority of Cerapedics’ competitors, Dr. Marx pointed to three of the company’s prospective human clinical studies where their product was exclusively used to regenerate bone during interbody spinal fusion. Competitive products like synthetic bone grafts, demineralized bone matrices (DBMs) and stem cell products generally have to be mixed with autograft material and, therefore, can’t support bone generation and spinal fusion by themselves.
“We’ve taken market share from allogeneic stem cell products because they have no data, and the only approval they’ve got is under the minimal manipulation of tissue status. They’re definitely on their way out,” Kashuba said. Fly by night companies selling cure-all stem cell treatments claiming to regenerate bone and provide other unsubstantiated health benefits have become the center of increased scrutiny by FDA, FTC and surgeon associations. In August 2019, FDA released a statement warning patients against undergoing unapproved and unproven stem cell treatments.
Dr. Marx and Kashuba claim that i-FACTOR’s track record of efficacy, safety and FDA compliance has been essential for building trust with surgeons and hospital networks and proving that their autograft replacement technology works. In perhaps what’s been the most affirming sign yet for the Colorado-based company, Cerapedics earned a crucial and highly exclusive spot on a list of recognized and recommended bone graft products published by the International Society for the Advancement of Spine Surgery (ISASS) in 2018.
“ISASS took it upon themselves to review over 400 bone graft materials and make recommendations to hospitals and administrators as to how they should categorize them,” Dr. Marx said. “They took it a step further and looked at what their regulatory pathways were and, most importantly, the clinical evidence available for each product to make clinical use decisions. It clearly shows that i-FACTOR and Infuse are in a category by themselves as the only two products that are supported by human clinical data.”
Dr. Marx noted that while many “crummy” and unproven bone graft products residing in the Class II category crowd the market and tarnish the reputation of technologies that are proven to work safely, ISASS’ recommendation has helped Cerapedics cut through the noise.
The need for bone grafting technologies in healthcare is well established, from aiding the functionality of surgically implanted medical devices to promoting bone regeneration after spinal fusion surgery. According to Dr. Marx, the original technology that preceded Cerapedics was discovered at the University of California, San Francisco, during the late ‘90s. “It was first brought to use in the dental and maxillofacial arena with a tremendous track record of safety and efficacy,” he said.
By Dr. Marx’s estimation, half a million American patients were treated with the technology for oral cavity and maxillofacial applications before the founding of Cerapedics, which began with the goal of leveraging the technology to promote rapid bone regeneration and healing in other parts of the body. Though i-FACTOR has been used effectively everywhere from “the base of the skull to the toes,” according to Dr. Marx, the majority of its use is for spinal applications.
i-FACTOR is a drug-device combination product. Its drug component consists of a 15-amino acid peptide that synthetically replicates the type-1 collagen segment that facilitates all cellular attachment in connective tissues. “When this peptide is synthesized and chemically ionically bound onto the surface of a calcium phosphate carrier, it will attract, attach, and activate bone-forming cells,” Dr. Marx said.
i-FACTOR is manufactured inside Cerapedics’ lab in the suburbs of Denver, Colorado. First, calcium phosphate raw material is incinerated at high temperatures before being smoothed, treated with heat once more, and washed. Then the 15-amino acid peptide is then soaked with the calcium phosphate particles in a chemical binding process.
According to Kashuba and Dr. Marx, Cerapedics is undergoing testing and development for a second-generation version of i-FACTOR, a process that’s already spanned seven years. Dr. Marx calls the i-FACTOR+ Matrix project a considerable undertaking, but he believes the product update is poised to disrupt the bone grafting market in terms of safety, rapid bone regeneration and fusion, and ease of intraoperative handling. Cerapedics recently announced Canadian approval for the product and is currently working toward finishing clinical trials and executing a U.S. market regulatory strategy.
“Our regulatory approval process has actually been somewhat in the fast lane because of our data,” Kashuba said. When asked what advice he’d give orthopedic device companies facing down long development and commercialization processes, he recommended looking for products that are clearly new and different. “Make sure it’s sound, safe, and great for patients––that’s the most important thing. But also, don’t be afraid to invest in trials and the data. They both take time to do, but it’s worth it.”
This article was updated on 12/4/2020 to include information about Wright Medical's AUGMENT product.
Patrick McGuire is an ORTHOWORLD Contributor.