Back To The Future: The Revenge Of Gene Therapy

Published: May 29, 2014

Plus, have big pharma layoffs created a new vicious cycle?

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BioPharm Executive: Back To The Future: The Revenge Of Gene Therapy

May 28, 2014

By Karl Thiel for

I remember being hugely excited about gene therapy back in the 1990s. The idea of using an engineered virus to shuttle corrected genes directly into the genome was elegant and appealing, and came with the (perhaps naive) hope that once the vectors were worked out, there was plenty of low-hanging fruit that could be addressed through an essentially plug-and-play approach with different genes.

Over the next several years, gene therapy became associated with clinical failures, including the controversial death of Jesse Gelsinger from an infection linked to the adenovirus used to shuffle genes into his cells. For much of the 2000s, it was associated with...well, not much at all. It seemed like there wasn't a whole lot going on, at least to judge by the headlines.

It turns out that wasn't quite true, and now we seem to be in something of a gene therapy renaissance. The current IPO window has seen the launch of Applied Genetic Technologies Corp. (AGTC, in March), uniQure (in February), Celladon (in January), and bluebird bio (last summer). None have been stunning in terms of post-IPO performance, but all except uniQure, they still trade above their debut price. (That's somewhat ironic, since uniQure has the world's only commercial gene therapy—Glybera, which was approved last year in Europe for the treatment of lipoprotein lipase deficiency.)

Spark Therapeutics, Juno Therapeutics, and Editas Medicine are among the more notable gene therapy companies to have raised big venture capital sums in the past year. And this month we can add a new company to the list: Lysogene—which this month raised $22 million to forward its gene therapy platform. Lysogene's strategy is to introduce corrected genes directly into the brain, initially with a focus on Sanfilippo syndrome Type A, a lysosomal storage disease.

Lysogene's focus perfectly sums up the new direction gene therapy has taken. The resurgent interest owes a large debt to the embrace of rare disease drugs as commercially viable. That means companies are less tied to going after the biggest prizes and have more flexibility to focus gene therapy to areas where an immune response is not an issue—specifically the eyes (Spark, GenSight Biologics, NightstaRx) and the brain (Lysogene, bluebird, Voyager Therapeutics). That's a stark contrast to the early approach, which was to go after the most widespread genetic illnesses, like cystic fibrosis.

All this progress, however, has attracted more attention—and competition—to the sector. Earlier this month, Regeneron announced a gene therapy collaboration with Avalanche Biotechnologies focused on—surprise, surprise—ophthalmologic diseases. The deal carries a high $640 million headline number, although with eight potential targets involved, the upfront may be relatively small (it was undisclosed). Still, Regeneron's interest in gene therapy follows on the heels of BioMarin Pharmaceuticals move into the sector, which began last year when the company licensed a hemophilia program from University College London and St. Jude Children's Research Hospital. (The company selected an IND candidate from the program earlier this year.) Novartis has had a hand in gene therapy ever since the 1990s, but has lately upped the ante, with the report this past December of some stunning success in a gene transfer technology to engineer T cells to attack leukemia. The drug, CTL019, could be on the market as soon as 2016 and become the first anti-cancer gene therapy.

Of course, gene therapy isn't the only therapeutic modality pioneered decades ago, seemingly forgotten, and then reborn. Antisense and its offshoot RNAi have also been marking major progress recently, with a commercial approval and many more products seemingly posed for success in the near-future. Antisense has an even longer pedigree than gene therapy (the concept actually goes back to the 1970s, while Ron Crystal's pioneering adenoviral work didn't begin until the late 1980s). The long road each has followed says something about the relative amounts of inspiration and perspiration required to bring groundbreaking new therapeutic approaches to fruition. I hope the next few years sees major commercial success for both these technologies. We can throw a huge '80s party—Rubik's cubes, vinyl albums, and drugs we never thought would see the light of day.

Where do scientists come from?

By the way, here's an interesting article if you haven't read it: Bruce Booth (of Atlas Capital) over at the LifeScienceVC blog talks about drug discovery talent and where it comes from. The main gist is that it takes a really long time to become truly adept in the multidisciplinary skills required for success in drug development. Being a brilliant post-doc doesn't cut it; you also need years in the field to gain hard-won experience, integrate "soft" learnings with hard science, and become R&D street-smart.

Moreover, the time it takes to gain this kind of expertise is a luxury biotech can't afford: They rely on hiring people who came up through Big Pharma. So you can probably see the problem coming: Big Pharma is no longer hiring newcomers. Indeed, they are reducing R&D pretty much across the board. In the short term that's perhaps good for biotech—lots of talent has been made available in the past few years—but in the long term it means no one is bringing new people up to speed. If biotech can't hire away these folks, how will they develop the drugs that Big Pharma is increasingly looking outside its own walls to acquire? There's more to it than that, of course—read the whole piece!

-Karl Thiel

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