The growth of intravenous thrombolysis (IVT) coupled with the advent—and ongoing expansion—of mechanical thrombectomy has seen acute stroke transform from “a diagnosable and hardly treatable condition, to a highly treatable condition”, over the past two decades. However, significant disparities in thrombectomy access exist across the globe, with uptake rates remaining especially low within many developing countries.
That is according to Shashvat Desai (HonorHealth, Scottsdale, USA), who—alongside Ashutosh Jadhav (Barrow Neurological Institute, Phoenix, USA)—recently spoke to NeuroNews to discuss Gravity Medical Technology’s mission to alleviate some of these disparities and ensure more patients have access to these potentially life-saving procedures.
A key building block leading to this mission was the MT-GLASS study, which was initiated back in 2020 as a means for elucidating disparities in thrombectomy care within individual countries, but also between different geographies. Published last year, MT-GLASS ultimately found “extremely low” global access to the procedure; median uptake worldwide sits at 2.79%, with rates dropping below 1% in poorer geographies within Africa and Asia.
“There’s a lot of regional variation,” says Jadhav, Gravity’s chief scientific officer. “The determinants of that are what you’d expect. One of the big ones is that low- and middle-income countries [LMICs] have much lower access than higher-income countries, so cost and infrastructure are certainly a big part of it.”
Among many contributing factors are the availability of operators and trained healthcare professionals, as well as medical equipment—as Jadhav notes, “some countries don’t even have CT [computed tomography] scanners”. Other barriers relate to matters that are often “taken for granted” in the western world. On this point, Jadhav recalls prior efforts to roll out a stroke awareness campaign in Ethiopia being hampered by the fact that there is no word for ‘stroke’ in the country’s predominant language of Amharic.
MT-GLASS did show, however, that gross domestic product (GDP) and other determinants of a country’s financial strength are undeniably among the most prominent predictors of thrombectomy access levels, and breaking down these economic barriers in order to “democratise” stroke treatment has become Gravity’s primary goal.
The Gravity mission
The company’s efforts to “close that gap” began in 2020 and have homed in on one specific yet critical point: the fact that existing devices used in thrombectomy procedures are “cost-prohibitive” for many countries.
“For example,” Jadhav explains, “the cost of a stent-retriever device is higher than the [average] annual income of an individual in India—they earn less than the cost of these currently available devices. That’s just not a sustainable or practical option.”
“Affordability is the question,” adds Desai, chief technology officer for Gravity, highlighting an issue that is almost alien to Europe and the USA, but prevalent across much of the rest of the world. “When a patient goes into a private hospital in India, the issue is who’s going to pay the upfront US$4,000–5,000 to buy the hardware to offer thrombectomy. But, if you can bring that down to a more tenable amount of US$2,000, that changes the equation to the extent where an additional two hundred million people can afford it.
“Every person does their own cost-effectiveness analysis in that situation. This concept is probably well understood by behavioural economists but is yet to be meaningfully translated to healthcare. We study cost effectiveness, but we assume the government will pay for everything from start to finish, and that’s not the case in most parts of the world. Given that the luxury of time is not an option in acute stroke treatment, affordable, cost-flexible devices are most impactful because, up front, the patient or their family is able to pay for it—that changes the game completely.”
Gravity has set out to create thrombectomy devices that can be produced at a lower cost and, in turn, made available to developing countries at more flexible price-points. Leading these offerings is its Supernova stent retriever, which progressed through animal testing in 2023, and evaluation in humans for the first time in February 2024, and has since received market approval in South-East Asia.
Preclinical evaluations involving Supernova provided signals that it was equivalent to market-leading stent retrievers from Medtronic and Stryker in strokes caused by ‘softer’, typically easier-to-treat clots, and could potentially be more effective in ‘harder’, more challenging ones. Subsequently, first-in-human findings derived from 10 patients in Pakistan enrolled in the prospective, multicentre, single-arm GRASSROOT study have seen “excellent” performance from the novel device regarding safety and efficacy.
Data disclosed at the 2024 World Live Neurovascular Conference (WLNC) and iCure Stroke joint meeting (7–10 May, Istanbul, Turkey) revealed that Supernova achieved modified thrombolysis in cerebral infarction (mTICI) 2b–3 recanalisation within three passes 90% of the time, and at the first pass 60% of the time, without leading to any device-related complications. These results led Dileep Yavagal (University of Miami, Coral Gables, USA), the global principal investigator of the GRASSROOT trial, to conclude that the device has the potential to “substantially advance” first-pass success rates as well as achieving Gravity’s aim of improving thrombectomy access across the world.
As of July 2024, more than 70 stroke patients have now been successfully treated using the device across Thailand and Pakistan, and Desai and Jadhav anticipate these numbers growing rapidly in the coming months—initially with the inclusion of patients in India and, later, with enrolments in Turkey and Romania, as the company targets European approval further down the line. As Desai puts it, GRASSROOT is set to create a diverse, “first-of-its-kind” dataset thanks to its basis in these developing countries.
The eventual goal for Gravity is to create a stroke thrombectomy ‘kit’ that incorporates its Supernova stent retriever, its Neutron aspiration catheter—for which first-in-human data from Thailand are expected to be presented later this year—and several other devices including microcatheters and guidewires. Jadhav notes that this will effectively mean the company can provide “the whole A through Z” as one bundle of products.
“This is the first time anyone has attempted to produce an affordable [thrombectomy] device kit,” comments Desai. “The example we commonly give is what really brought cardiac stenting procedures to the fore and made them commonplace across the world: the availability of affordable cardiac stents. It took 30–35 years for them to do that. What we are doing right now could shorten that time from three decades to half a decade for acute neurointervention. So, I think we’re trying to address a socioeconomic challenge as much as a healthcare challenge.”
Time is brain—and money
So, how has Gravity attempted to achieve these lower price-points while maintaining the safety and efficacy seen in more established thrombectomy devices?
Desai and Jadhav were naturally reticent to give away all of their secrets, but did reveal that utilising novel in-silico simulation techniques alongside European partners has enabled them to “drastically reduce” the costs associated with research and development. In addition, the first-pass effect rates they have observed in preclinical testing appear to be significantly higher than those associated with established devices, meaning fewer individual devices—and, therefore, reduced costs at the hospital level—would theoretically be required per patient to achieve treatment success.
Desai also highlights Gravity’s “cost-conscious” regulatory approach, which involves generating clinical data in countries like Turkey, Thailand and India where levels of stroke expertise are high but clinical stroke research costs are lower, rather than more expensive geographies like the USA or Western Europe.
“We’re trying to do things in efficient ways, and we’ve moved pretty quickly,” Jadhav comments. “If you look at our timeline, we’ve moved from prototyping to flow models, to animal testing, to human testing within about three years. That’s another reason we’ve been able to save costs—by just streamlining our process. If you take 10 years to get to this point, you can imagine that it’d be much more expensive.”
Jadhav goes on to state the testing of devices and drugs alike in the USA has become somewhat restrictive in recent years, owing to how expensive it is to conduct clinical trials. And, “it’s to our detriment, from a commercial standpoint but also a research standpoint”, he adds, alluding to the fact that other regions—Europe and China, for instance—are currently able to conduct large-scale studies in the stroke space more efficiently.
“Basically, by the time you get to market, as a company, you’ve built up a lot of debt just to get to that point, and then it’s hard to introduce devices at a reasonable price-point,” Jadhav says. “The cost issue is on everyone’s minds and the solutions are difficult. I think we’ve come up with some innovative ways to reduce that cost to get to market and I do suspect that, with time, a lot of these device trials will be conducted in LMICs, as they develop the infrastructure to support that.”
Expanding thrombectomy
Gravity’s attempts to buck the trend of prioritising US and European device approvals prior to entering Asia and other markets—instead opting to complete much of its early clinical research and initial approvals in Asia before moving into Europe and then, eventually, the USA—may carry a number of wider implications beyond simply making its own technologies more affordable.
With a combined population exceeding 300 million people, Thailand and Pakistan are examples of LMICs that are very large yet rarely see involvement in clinical stroke research. However, this “has to start somewhere”, according to Gravity chief executive officer Kunakorn Atchaneeyasakul, who is hoping the two countries’ participation in early studies of the company’s devices will help create a pathway for additional studies in the future.
“No one’s ever approached these geographies for these kinds of studies, so that’s been a very satisfying part of this endeavour,” Jadhav says, noting that studies like GRASSROOT can aid these countries in creating a template and the appropriate infrastructure within which to conduct more trials inside and indeed outside the stroke space. Processes around enrolment criteria, patient consent and ensuring long-term follow-up are all potential areas of which centres in LMICs can build a greater understanding—“and there’s an appetite to do it, they just haven’t been approached”, Jadhav adds.
Furthermore, while an increasing amount of research is now coming out of China, much of the randomised controlled trial data on thrombectomy come from Caucasian patients in Europe and the USA, and have been somewhat generalised across the rest of the world. This is in spite of known discrepancies between populations, such as the fact that intracranial atherosclerotic disease (ICAD) is a more prevalent cause of acute stroke among Asian and Black people.
“It’s possible that we need better devices for those mechanisms of stroke,” Jadhav notes. “In some of these countries, we also see more inflammatory and infectious mechanisms of stroke that we don’t think about as commonly in Europe and North America. That’s another gap that we’re understanding more by engaging these countries in our first-in-human studies. Just anecdotally—and it’s a small sample size—but we are seeing more ICAD in the Thai population and the Pakistani population than we would’ve expected from the original 2015 and 2018 [thrombectomy] trials. That should be really educational as we try to broaden treatment availability, as we may need to think about the devices differently too. Maybe, there are going to be different devices that are necessary for different stroke mechanisms.”
Desai and Jadhav highlight possible anatomical discrepancies between patient groups too, such as the middle cerebral artery (MCA) being slightly smaller among some Asian populations—a phenomenon that is still being investigated but could have implications for device design. They also comment that the vast majority of published clot-analysis data to date have come from North America and Europe, but that Gravity’s research efforts may help generate more of these data from Asia and other parts of the world.
“There are some differences and, because these populations were under-sampled in prior studies, we’re starting to get a fuller picture by looking at these devices in these populations,” Jadhav concludes.
