January 23, 2025 | A lot is at stake in obesity drug development, heightening the focus of pharma sponsors on producing the right evidence to support a label claim and differentiating their products in the rapidly growing weight management pharmacotherapy market. It’s also the rationale for the industrywide DECODE Obesity initiative of Ametris (formerly ActiGraph) looking to expand the range of outcome measures beyond weight loss, according to CEO Jeremy Wyatt.
“It’s about the overall health of the patient, and this is supported by the FDA’s PDUFA [Prescription Drug User Fee Act] initiative,” he says. Recent reauthorizations have sought to better understand what matters most to patients in the agency’s review processes.
The industry consortium known as DECODE—short for Digital Endpoint Collaboration for Outcomes Development—had its first foray into patient-centric digital measures with the 2023 launch of efforts to validate nocturnal scratch as a regulatory-accepted endpoint in drug development studies for psoriasis and eczema. The research collaboration endeavors to “create a win-win situation in which pharmaceutical companies can accelerate what they’re doing, and the FDA gets evidence to evaluate treatment benefit to the patients,” says Wyatt, referring to how a drug impacts patients’ everyday disease experience.
For DECODE Obesity, four of the largest pharma sponsors have formally signed on as partners: Roche, Eli Lilly, Novo Nordisk, and, most recently, AstraZeneca. As founding members, they will have early access to the validated algorithm and evidence generated in an ongoing observational study as well as be engaged in forthcoming discussions with the FDA and European Medicines Agency (EMA).
When it comes to obesity, which affects about half the U.S. population, “weight loss is cardinal,” Wyatt continues. “But to compete in this market, new drugs must show that patients are not only losing weight but are also living a fuller life. There’s now a higher level of expectations coming from the FDA and consumers.”
Concern about the patient experience with extremely popular GLP-1 drugs—e.g., Ozempic, Wegovy, Mounjaro, and Zepbound—is particularly high regarding muscle loss, says Sylvain Zorman, director of digital solutions strategy at Ametris. Research has found that up to 40% of weight loss could come from lean mass, which in addition to physical mobility plays important roles in metabolism, structural support, immune function, and overall longevity. “But at the same time [patients] are losing weight, meaning it takes less effort to do movements so there’s a complex interplay between all those factors that are not well understood.”
One in eight Americans has reportedly used GLP-1 drugs for weight loss, so “it is not a small thing,” says Zorman. Expectations are that the trend will only accelerate, he adds.
Although Ametris is most often associated with being a digital device provider—it was, after all, a pioneer in the space for over two decades—it has more recently matured into a company that develops qualified clinical outcome measures, says Wyatt. “We’re building a toolset that pharma sponsors can use to help understand how a drug is impacting a patient population ... and that’s difficult [to do] because it means you’re recruiting patients and running a clinical study.”
The DECODE Obesity initiative involves an observational study financially supported by its pharma partners that will produce a digital measure that Wyatt believes will ultimately benefit every obesity trial that is going to be conducted over the next decade. The anti-obesity drug pipeline includes hundreds of compounds, many newer generations of GLP-1 drugs already in late-stage development, Zorman notes.
Wearables will be used in the 30-patient study in Massachusetts to validate measures of physical activity, functional mobility, and sleep as clinical endpoints in the context of obesity, says Zorman. Although the LEAP device of Ametris is doing the measurement, pharma partners may ultimately opt to use any other tools of their choosing. Participants agree to wear the device at home for one month of continuous monitoring and to participate in a battery of in-lab tests.
The patient engagement piece seeks to better characterize the meaningfulness of the measures to participants as well as usability of a wearable device to do the measurements, Zorman says. Ensuring that a wearable of this type would fit seamlessly into their daily life will be captured largely by an end-of-study questionnaire.
Determining the importance of the measures to patients is more nuanced and complex, involving lengthy and structured interviews where investigators probe each of the three domains. The question is not only do patients want to walk more, he offers as an example, but how much more—e.g., 1,000 steps or 10% more per day.
Patients with obesity want to be more physically active and have some mobility-related limitations but might care less about their total number of steps than a practical metric such as the longest walking bout they can reasonably tackle, says Zorman. That’s an important detail that will change the way activity data will get analyzed and reported.
One difficulty is that some patients might not complain about being physically limited simply because they have grown accustomed to a more sedentary way of life, he says. But their quality of life would nonetheless benefit if they were to become more physically active.
Ametris and its pharma partners will be engaging with the FDA as well as the EMA to obtain regulatory buy-in, Zorman says. With DECODE Nocturnal Scratch, each of the meetings involved about 50 people from the respective agencies, showing the interest and support of regulators for this initiative.
“We’re all pushing in the same direction,” says Wyatt, pointing to both PDUFA and the FDA’s finalized guidance in 2022 on the use of digital health technologies in clinical trials. “As a company, we also have a great relationship with the FDA and EMA and now China’s FDA [National Medical Products Administration],” which could be a part of future DECODE work.
The name change, from ActiGraph to Ametris, happened a year ago and reflects the company’s shift in focus from motion, sleep, and behavioral monitoring to “measures across a huge stratum of therapeutic areas and subsectors that are not beholden to one sort of technology,” says Wyatt. The rebranding followed the acquisition of the Biofourmis Connect platform, encompassing AI-driven software, algorithms, and data ingestion for a variety of sensors.
DECODE Nocturnal Scratch, a project that build on another initiative from the Digital Medicine Society, began during Ametris’ transition phase to a company more broadly devoted to adding efficiency to the drug development process, he says. In developed countries, atopic dermatitis and eczema affect about 10-20% of children and patients care a whole lot more about better controlling the urge, often subconscious, to itch during sleep than the size of their rash. “It’s terrible; these kids are waking up with blood on their sheets where they have scratched all night long.”
DECODE was birthed out of the clinical need for “a digital measure to give a continuous observation of patients doing something they don’t even know they’re doing,” says Wyatt. “They’re trying to sleep, not count how many times they scratch.”
This led to the development of an algorithm to quantify nocturnal scratching, which is now a validated tool that is being deployed in clinical trials. Pharma companies conducting studies on dermatological conditions characterized by chronic itch have “a tool they can leverage to make better drugs,” Wyatt says.
Drugmakers have multiple other unmet needs where DECODE could play a role, including better measures of the effectiveness of Parkison’s disease treatments than timed finger tapping, he adds. But next up for the consortium, based on the pipeline of all the top 20 pharma companies doing business with Ametris, will be in the oncology area. A press release on the matter is expected this spring.
“This is not something we could do by ourselves,” stresses Zorman. Partnering pharma sponsors determine the study design and co-write the protocol and study-related contracts. “It takes a village to make those measures.”
“It's not just a partnership between Ametris and the pharma sponsors who have the need,” Wyatt adds. “It’s also about the health authorities who are being brought into the conversation to make sure we’re doing this the right way.”
The payer perspective on currently marketed GLP-1 drugs is that the cost and duration of treatment are unsustainable. Because of this, they have been “raising the bar” for coverage and reimbursement of those treatments, Zorman reports. “One of the big pushbacks from the payer is when does it end … [or] do you take this treatment forever?” In the UK and other countries, payers will sometimes limit coverage to two years and then require beneficiaries to go back to dieting and exercise before allowing drug treatments to resume. They’re looking for evidence of treatment benefits “based on data,” he says.
Founding members of the DECODE Obesity initiative who provide most of the financial support also enjoy the most benefits, including influencing the study protocol and the type of obese patients who can participate, getting early access to the algorithm and study data, and enjoying an audience with regulatory bodies for a better read on their perspective, says Zorman. A second tier of collaborators are still being sought, and they will get all the evidence generated by the study as well as priority access to the algorithm that is being developed by the consortium.
Targeted completion date for the final report on the initiative is the first quarter of 2027. In the interim, Ametris will remain “extremely flexible in how we take in partners … we are eager to learn from them,” says Wyatt. “No one has ever done this.”
One unique aspect of the initiative is that the focus is on collecting raw sensor data, not making companies use a particular measurement device, he says. “With nocturnal scratch, well before we had an algorithm ready, our partners were already in phase 2 and 3 studies collecting data. The readouts happened later … and we needed to go back and interpret the data we had.”
Similarly, Ametris is in discussion with its latest set of partners about “getting ahead of the end” by initiating data collection from patients that is likely to be germane to the digital outcome measures now under development for obesity drugs. “There’s no need to wait,” Wyatt says.
The DECODE Obesity initiative was built to address the lack of standardized objective ways to measure how GLP-1 obesity treatments affect daily life in terms of sleep, mobility, and ability to function, and “it isn’t theoretical,” he stresses. “It’s happening right now at scale … [and] it’s shifting obesity care towards long-term, whole-person outcomes.”
Many Ametris employees, including Zorman, formerly worked for some of its big pharma customers. It was during those interactions that they came to believe that clinical research could be digitally transformed by what Wyatt describes as “the only unified platform in the world” for turning complex, real-world patient data into meaningful evidence.