Granite Bio Innovation

The formal, legal answer is yes: the federal regulatory regime effectively blocks it entirely. But there are near-term political solutions to this problem, and some are already happening. The FDA’s commissioner and chief medical officer recently acknowledged in NEJM that there is no viable federal regulatory pathway for offering bespoke therapies at commercial scale. That’s also my legal opinion after talking to patients, providers, and innovators about emerging therapies. The FDA went on to outline a proposed “plausible mechanism pathway” to address this problem. But this pathway can’t accommodate bespoke therapies at commercial scale either. It would require a well-characterized, natural history of each disease and require each patient to provide a mouse model or equivalent nonclinical model before getting FDA approval. This kind of thing is typical of federal agency attempts at supporting innovation. In earlier guidance on rare diseases, the FDA said they may accelerate approvals by requiring only a single-arm trial instead of an RCT. So how did we get here and what are the solutions? The FDA’s congressional mandate comes from two fossilized, FDR-era statutes: the FD&C Act and the PHS Act. The PHS Act extends FDA regulation to all biologics—which it defines to include all viruses, vaccines, proteins, and “analogous products” intended to treat or cure any condition. The FDA views bespoke gene therapy as a biologic. Any biologic can also be regulated as a “drug” under the FD&C Act. A “drug” includes any “article” intended to affect “any function of the body.” This is as broad as it sounds. For example, courts have held that your own stem cells are a “drug” if they are cultured in a solution before being reintroduced to your body. But—and this is the key to any near-future solution—everyone appreciates that the FDA has vast non-enforcement discretion. The FDA has never regulated the practice of IVF, for example, even though it could clearly choose to do so under FD&C and/or PHS. Instead, the FDA views IVF as the practice of medicine. This hasn’t made IVF into the Wild West. IVF is still subject to four other kinds of legal authority: state statutory rules, state professional codes, state regulatory agencies, and medical malpractice liability. That is enough to prevent many abuses. Individualized gene therapy and other bespoke therapies could simply be regulated the same way. Gene therapy should be regulated as gene surgery. The idea that Congress is going to overhaul FD&C and PHS anytime soon is ridiculous. But we have two good solutions that simply go around Congress. First, 200+ Americans have already received experimental treatments under state right-to-try laws, which operate outside the FDA approval framework. While the FDA could legally preempt these laws, it has never invoked preemption in response to a state-compliant right-to-try treatment. Most state right-to-try laws are far too narrow and weak to be used at scale. But in the last few years, expansive new laws have been enacted in Montana, Florida, and New Hampshire which could accommodate commercial-scale experimental therapies. New Hampshire's proximity to Boston makes us ideally positioned to become a hub of emerging biotech. These laws are promising. The FDA is unlikely to renege on 10 years of de facto non-enforcement just because more patients are being treated. In the same way, the DEA has allowed a multibillion-dollar marijuana industry to grow in some states under three different presidents. The letter of the law says the DEA could entirely preempt these laws tomorrow. Political reality says they will not. Secondly, the FDA can promulgate memoranda adopting new, more limited interpretations of the law and/or formalizing non-enforcement policies. Ideally, the FDA should say that it has gotten IVF right and gene therapy wrong. The FDA should declare that it now considers bespoke therapy, at least under certain conditions, to be part of the practice of medicine. Eventually, we should scrap the entire FDR-era statutory framework and pass new laws grounded in the reality of AI-based sequencing, gene editing, and other bespoke therapy tools. In the meantime, though, patients can’t wait.

this is actually insane > be tech guy in australia > adopt cancer riddled rescue dog, months to live > not_going_to_give_you_up.mp4 > pay $3,000 to sequence her tumor DNA > feed it to ChatGPT and AlphaFold > zero background in biology > identify mutated proteins, match them to drug targets > design a custom mRNA cancer vaccine from scratch > genomics professor is “gobsmacked” that some puppy lover did this on his own > need ethics approval to administer it > red tape takes longer than designing the vaccine > 3 months, finally approved > drive 10 hours to get rosie her first injection > tumor halves > coat gets glossy again > dog is alive and happy > professor: “if we can do this for a dog, why aren’t we rolling this out to humans?” one man with a chatbot, and $3,000 just outperformed the entire pharmaceutical discovery pipeline. we are going to cure so many diseases. I dont think people realize how good things are going to get

this is actually insane > be tech guy in australia > adopt cancer riddled rescue dog, months to live > not_going_to_give_you_up.mp4 > pay $3,000 to sequence her tumor DNA > feed it to ChatGPT and AlphaFold > zero background in biology > identify mutated proteins, match them to drug targets > design a custom mRNA cancer vaccine from scratch > genomics professor is “gobsmacked” that some puppy lover did this on his own > need ethics approval to administer it > red tape takes longer than designing the vaccine > 3 months, finally approved > drive 10 hours to get rosie her first injection > tumor halves > coat gets glossy again > dog is alive and happy > professor: “if we can do this for a dog, why aren’t we rolling this out to humans?” one man with a chatbot, and $3,000 just outperformed the entire pharmaceutical discovery pipeline. we are going to cure so many diseases. I dont think people realize how good things are going to get