Abundant funding, sparse data: San Francisco startup backs 'real world' model for rare disease drug development
Rare diseases, a field of drug development where funding far outstrips research on often poorly understood conditions, can leave scientists often reinventing the wheel to engineer therapeutics.
RDMD, a San Francisco-based company, has a plan to address that impasse by serving as a conduit between the patient and the drug developer. The platform courts patients with rare diseases by helping them access medical records and participate in research, while for drug developers, the company structures the compiled data in an effort to build research programs and develop an evidence base palatable for regulatory authorities.
Until now, companies big and small in the space have been stuck looking for patients in 10, 20 or more hospitals, depending on the disease, noted co-founder Nancy Yu in an interview.
“So most companies are growing their internal teams, as well as working with contract research organizations, and subcontracting to up to sometimes 15 different software vendors to manage the process,” Yu said.
Streamlining this process, and helping patients themselves access their data and participate in research, could change the way the rare disease drug development is conducted, RDMD hopes. This lofty goal was given a $14 million injection on Thursday in a Series A round led by Spark Capital, a venture capital firm that has previously backed companies such as Slack, Twitter and Oculus.
“At the end of the day, rare disease just requires a different model for drug development,” Yu said. “The challenge is really understanding what the disease actually is and how you can best create and design a program around evidence that exists. It’s really hard to design a successful program if you don’t know much about the disease.”
That requires patient data which, apart from being scarce, are not all accessible in one universal electronic medical records system.
“So we get permission from patients … to be able to get all their records from their various facilities. And that’s both because we want to empower patients with that choice of opting in to participate in research, but it’s also a necessity operationally for us to be able to get that information, because it doesn’t sit in a central database somewhere,” she said.
With the patient’s consent, the data are then collated and disseminated to companies to give them a comprehensive understanding of the disease, and consequently, design clinical trials, determine what endpoints and biomarkers are relevant, and even educate payers and insurance companies so they can cover the drugs upon approval.
There’s a lot that patients can contribute to in terms of research that doesn’t necessarily involve participating in a clinical trial, she added.
“For example, some of this data could be used to support and eliminate the need for a placebo control arm because you’re just looking at data that already exists in the real world around patients and their natural progression of disease,” Yu said. “And so that’s certainly something that everyone is very focused on and hoping to use the data for.”
Sound familiar? A New York-based tech company called Flatiron Health that was swallowed by Swiss giant Roche in 2018, has similar plans to use real-world evidence to replace more traditional clinical trial data to help the FDA make decisions for cancer drugs.
But traditional randomized controlled trials (RCTs) are considered the gold standard to prove if a compound or intervention is safe and effective for its intended use — they are used to show that a benefit or adverse event observed is not a matter of chance or bias.
But given limitations such as strict inclusion criteria, which typically disqualify older patients and those suffering from co-morbidities, RCTs can be an inaccurate representation of patients in the real world. But skeptics criticize that relying solely on real-world evidence could be dangerous, as the process has the potential to introduce researcher biases, and is not subject to the same methodological rigor.
That being said, unlike cancer drug development, rare disease trials are often hampered by slow enrollment due to the scarcity of patients — and the FDA requires a much smaller body of evidence for decision making. Sarepta Therapeutics’ pioneering Duchenne muscular dystrophy (DMD) drug Exondys 51, for instance, was approved on the basis of a tiny non-placebo controlled trial that compared the effect of the drug to the natural course of the disease.
Despite stiff opposition from within and outside the agency from critics who said data were insufficient to warrant approval, the FDA cleared the drug for use in a subset of patients with the rare muscle-wasting disease in 2016, prompting some to suggest the agency had bowed to pressure from patient advocates. Only in 2019 did Sarepta submit plans for a confirmatory trial, which is expected to be completed by 2024. But in the meantime, the company has since secured another DMD approval on the basis of a 24 patient study.
Yu, who previously worked with consumer genetics company 23andme, set up RDMD in late 2017 soon after co-founder Onno Faber was diagnosed with a rare genetic disease called NF2 (Neurofibromatosis Type 2), which affects 1 in 30,000 people.
“And so when we got together, it was really to figure out how do we tackle this — there are 7000 conditions and like one in 10 people have a rare disease that in aggregate, it’s a really big problem,” she noted.
On Thursday, the company also unveiled a partnership with Belgium-based drugmaker UCB for up to five years to work on progressive supranuclear palsy (PSP), a rare neurodegenerative disease.
In addition, RDMD is also partnering with patient advocacy organizations and physician consortiums across 12 conditions, including the Children’s Tumor Foundation, Cure Sanfilippo Foundation and National Tay-Sachs & Allied Diseases Association.
The Series A round also included the participation of existing seed investors Lux Capital, Village Global and Garuda Ventures, and new investor Maveron. The money will be used, among other things, to expand into a further 20 rare conditions and ensure the continuity of research programs throughout the Covid-19 pandemic.