Crispr Might Actually Live Up to Its Immense Hype

(Bloomberg Opinion) -- From the dawn of Crispr in 2012, medical scientists have recognized the gene-editing tool's potential to treat, or even cure, genetic diseases. New data from Intellia Therapeutics this week make their hope more realistic than ever. The company's Crispr therapy was able to significantly lower patients' levels of a misfolded liver protein and keep them low for months.

This comes as very good news for many biotech companies racing to develop therapies that stop the human liver from making bad-behaving proteins.

The Nobel prize-winning Crispr technology is moving from concept to clinic at breathtaking pace. Intellia is the first company to demonstrate success in so-called “in vivo” editing — that is, in living human cells. (The field has also seen some early good results in “ex vivo” editing, where cells are removed from the body, edited in a lab and then given back to a patient.)

Intellia's data came from a phase 1 trial of a therapy it is developing with Regeneron Pharmaceuticals that reduces output of the protein transthyretin, or TTR. In people with TTR amyloidosis, the liver makes a misfolded version of this protein, which then clumps together and builds up, causing damage to organs and nerves.

Last June, Intellia offered early data on the first six people who were given the drug. Among those who got the highest dose, blood levels of the errant protein dropped on average by 87%. The next question was, could the effect be improved at higher doses? If so, how long would it last?

The new data provide some answers. Nine more people added to the trial received one of two higher doses of the drug. So far, it appears that the higher the dose, the better it knocks out the gene.

Gene-editing experts are even more excited about the treatment's durability. Intellia's data show that protein levels stay low for at least 12 months after the Crispr therapy. Although it will take years to learn whether this will be a lifelong fix, the data suggest that a one-and-done treatment is at least a possibility.

In the gene-editing world, these new data have brought “not just a collective sigh of relief that nothing bad happened, but also a fairly audible ‘Woohoo!'” says Fyodor Urnov, director of the Center for Translational Genomics at the Innovative Genomics Institute.

The next hurdle for Intellia will be to show that its Crispr therapy is as good as or better than two existing drugs for TTR-amyloidosis: Alnylam Pharmaceuticals' Onpattro, which is administered once every three weeks, and Ionis Pharmaceuticals' Tegsedi, which is given weekly. Intellia's early data suggest that its drug can more fully suppress TTR production, but the company will need to prove that the effect translates into actual benefits for patients. That means demonstrating in a clinical study that it can slow or reverse the damage caused by the build-up of those protein plaques.

Another key test for Intellia, and more generally for the gene-editing field, will be to show that its Crispr therapy won't cause dangerous side effects down the road. A constant worry about any gene therapy is that it may make so-called “off target” cuts in otherwise healthy DNA that could lead to cancer.

If further data from Intellia's trials check all the boxes on safety and efficacy, the company will be poised to take a page from the playbook of another Nobel prize-winning technology, RNA interference. That approach uses molecules called small interfering RNAs to turn off production of errant proteins.

Alnylam spent more than 16 years working out how to get those siRNAs into liver cells. But once it struck upon a successful delivery system, designing new drugs by swapping in new siRNA became fairly straightforward. The biotech firm now has multiple approved drugs and a robust late-stage pipeline.

Intellia's data suggest that gene-editing companies could adopt that same kind of plug-and-play approach, at least for liver diseases. “In my mind, the door to the liver is now wide open,” said Kiran Musunuru, a cardiologist at the University of Pennsylvania's Perelman School of Medicine and a founder of Verve Therapeutics, which is developing a type of gene editor that swaps one base for another.

Biotech companies aspire not only to shut down bad-behaving proteins, but also to correct larger stretches of DNA or to insert new genetic code. Delivering those types of approaches to the target cells, even in the liver, remains a high hurdle for the field.

Another wrinkle for Intellia: The U.S. Patent and Trademark Office ruled yesterday that the Broad Institute of Harvard and MIT owns the intellectual property underpinning the first generation of Crispr gene editors. Intellia and several other companies licensed the technology from the University of California, which has claimed to own the IP and says it plans to appeal the Patent Office decision. Shares of Intellia and others sank on the news, but analysts think the universities will eventually establish cross-licensing agreements that won't delay development in the Crispr pipeline.

In any case, Intellia's data is a big step toward proving that Crispr can live up to its immense hype — at least for some genetic diseases. The question is whether companies will be able to crack the delivery problem and realize the technology's full potential.

More from other writers at Bloomberg Opinion:

Can Moderna Buy Its Way Into the $200 Billion Club?: Max Nisen
Crispr Is Still Promising, Even If Editas's Experiment Falls Short: Max Nisen
Crispr Gene-Editing Breakthrough Is a Big Deal. How Big?: Sam Fazeli

This column does not necessarily reflect the opinion of the editorial board or Bloomberg LP and its owners.

Lisa Jarvis, the former executive editor of Chemical & Engineering News, writes about biotech, drug discovery and the pharmaceutical industry for Bloomberg Opinion.