To the uninitiated, the Food and Drug Administration might seem like a mean old troll bent on preventing new drugs from reaching patients, but that just isn't the case. In fact, the agency just listed some ways it intends to make developing new gene therapies a lot easier.
A clear set of goals is an important step for the future of gene therapy development, but the FDA's going to help some experimental treatments reach patients faster than others. Here's what you need to know about the agency's intentions and some gene-editing stocks that stand to benefit.
1. A shorter path for some
The FDA's latest guidance isn't set in stone yet, but the agency intends to offer accelerated approval for gene therapies that appear to offer one-shot cures. In a nutshell, the agency's looking for candidates that can cure diseases caused by a single defective gene.
That's good news for Novartis (NVS -0.28%), a big pharma that acquired a gene therapy developer for $8.7 billion last year. Zolgensma is under review after succeeding down the more traditional pathway, but the guidance bodes well for possible treatments to come. Zolgensma essentially infects nerve cells with a functioning copy of a gene that allows patients to produce something they couldn't previously due to the faulty gene they were born with.
Zolgensma treats type-1 SMA, a debilitating disorder that leaves infants unable to breathe without a ventilator before they reach their first birthday. Accelerated approval isn't a big deal for disorders like this because it doesn't take very long to measure outcomes. If Novartis uses the platform it acquired to develop new gene-replacement treatments for slower-moving disorders, the FDA's willing to review them if they simply meet goals that should lead to improved outcomes down the line.
Sarepta Therapeutics (SRPT -2.74%) is testing an experimental Duchenne muscular dystrophy (DMD) treatment that could benefit from the FDA's new guidelines. This progressive muscle-wasting disorder is caused by a lack of dystrophin, a protein that plays a role in maintaining muscle. Boys that inherit the disorder usually begin tripping over their own feet a few years after they're born, but usually don't become wheelchair bound until the age of 12.
That's just too long a stretch to measure differences between small numbers of patients. The FDA's stance suggests an experimental treatment from Sarepta that plants a functional micro-dystrophin gene into muscle cells has a shot at accelerated approval. The candidate, AAVrh74.MHCK7.micro-Dystrophin, could receive an FDA review faster than expected along with a name that doesn't make you think there's something wrong with your screen. Investigators found micro-dystrophin in four-fifths of muscle fibers sampled, which appears to help the entire dystrophin-associated protein complex do its job as intended.
The FDA's recent letter was specific to neurodegenerative disorders, but the stance suggests the agency could be willing to grant Sarepta's micro-dystrophin candidate an accelerated approval based on the presence of functional dystrophin in muscle tissue after several months. That's a lot better than waiting years to try measuring significant differences in patients' ability to walk compared to those left untreated.
Check out the latest Sarepta Therapeutics earnings call transcript.
2. A longer road for others
The FDA was clear about what kind of new gene therapies for neurodegenerative diseases it would send down the traditional approval route. New drug candidates that alter the course of a disease by influencing the production of proteins thought to play a role aren't going to receive a review until they have outcome data to back it up.
For example, we don't know exactly what causes Alzheimer's disease and there's probably more than one gene at play. A company that wants to tackle Alzheimer's disease with a new gene therapy will still need to prove it slows the rate of cognitive decline with a long study before the FDA will even look a new drug application.
3. A helping hand for CAR-T developers
Chimeric antigen receptor-modified T-cells (CAR-T) that go after cancer are incredibly effective, but manufacturing them is a complicated process. When it comes to biologic drugs, the manufacturing process and the drug are generally considered inseparable from a regulator's viewpoint.
That means Gilead Sciences can't even apply manufacturing technique upgrades that could make its CAR-T manufacturing process faster without running new studies. That's a problem because it can take weeks to get a patient's CAR-T therapy ready to be reinfused.
The FDA wants to introduce ways to improve the CAR-T manufacturing process without necessarily requiring new clinical trial results. When a bridging study is necessary, the FDA may be willing to accept real-world data after the change has been introduced.
The fun's just getting started
The FDA hasn't made these proposals part of its official guidance for drugmakers yet, but it probably will, because there's a tsunami of new gene therapy applications heading its way.
By 2020, the agency predicts it will begin receiving 200 applications per year to begin clinical trials with potential new gene therapies. By 2025, between 10 and 20 new gene therapies will enter the market each year, and that's the FDA's estimate. A regulatory agency that behaves like a sensible partner instead of a fixed tollgate is going to sweep a lot of debris from the path in front of Sarepta and its gene-editing peers.