done the kind controlled clinical trials the FDA considers necessary to support those claims under federal law. 23andMe looks especially silly for cutting off communication with the FDA several months ago, then deciding to launch an all-out consumer marketing blitz with a goal of getting 1 million customers for its $99 test. Truth is, 23andMe and the FDA are both entering some murky, uncharted waters, and both parties need to find their way forward. Over time, consumers are going to want to take some control over their genetic information, and that means a new kind of regulatory framework will need to be put in place. It just might take a few years. Whether it’s 23andMe, or some other company that figures it out, we’ll just have to see.
Companion diagnostic tests. Remember when Pfizer won FDA approval of crizotinib (Xalkori) for the small percentage of lung cancer patients with mutated ALK genes? The drug was approved alongside a companion diagnostic test that helped oncologists select which lung cancer patients had the gene variation that made them good candidates for the drug. A similar drug/diagnostic story played out around the same time in 2011 with Roche/Daiichi Sankyo’s vemurafenib (Zelboraf) which was approved for use in BRAF-positive melanoma patients. Two years later, I haven’t seen many other stories like this, and some of the more exciting drugs are coming forward without companion diagnostics. There are challenges in getting different development teams, with different deadlines, budgets, and profit motives, all rowing together in the same direction for a drug and diagnostic. But this remains a powerful idea, as healthcare reform is putting more pressure on everyone to squeeze the waste out of the system.
RNA therapies for Duchenne Muscular Dystrophy. Patients and their families with Duchenne Muscular Dystrophy have never seen so much hope, and disappointment, in one year. Cambridge, MA-based Sarepta Therapeutics (NASDAQ: [[ticker:SRPT]]) and Netherlands-based Prosensa (NASDAQ: [[ticker:RNA]]) both offered patients a prospect that RNA-based therapies might provide a means to help them produce more dystrophin to make their muscles work. Prosensa went public earlier in the year on excitement for its data, then promptly failed in a pivotal clinical study. Sarepta has gathered some encouraging data from a small study of 12 patients, and said in July that it planned to seek accelerated approval from the FDA on the basis of that study. But before the year was out, spooked by the Prosensa failure, the FDA told Sarepta such an application on a thin data set would be premature. Unless Sarepta can pull an amazing reversal, it is likely at least a couple more years away from reaching the market, if it ever gets there.
GSK’s malaria vaccine. GlaxoSmithKline has spent more than $300 million on developing a vaccine for malaria called RTS,S. The Bill & Melinda Gates Foundation has keen interest, and has put a lot of money to work here in a program that could theoretically save millions of lives in the future. Yet, as more follow-up data rolls in, the vaccine is disappointing, offering protection to fewer than half of infants who get vaccinated. Most of the great vaccines we take for granted today protect more than 90 percent of people from infection. One can only hope that researchers learn something from the RTS,S experience that can be applied to something that boosts the protection rate much higher.
Stem cell therapies. It was 15 years ago that University of Wisconsin biologist James Thomson made the cover of Time for his work in cultivating the first lines of human embryonic stem cells. It was exciting, opening the door to regenerative medicines, and it triggered a long-running bioethics debate. Two years have now passed since stem cell trailblazer Geron dumped its stem cell therapy intellectual property, including a program to treat spinal cord injury. This year, Madison, WI-based Cellular Dynamics International—a company co-founded by Thomson—went public. It has had success with creating a newer generation of induced pluripotent stem cells that can be used to help test experimental drugs in the lab. That’s great news for drug developers, who need more predictive models to increase the chances of success in human clinical trials. But are stem cell-based therapies helping paraplegics get out wheelchairs and walk again? Not even close.
Nanopore DNA sequencing. Oxford Nanopore wowed the genomics world almost two years ago with what looked like the next big thing in superfast, supercheap DNA sequencing technology. We’re still waiting for someone to deliver on the promise, who can combine speed, low cost, and accuracy.
Climbing up the Slope of Enlightenment
RNA interference, via subcutaneous delivery. Cambridge, MA-based Alnylam Pharmaceuticals (NASDAQ: [[ticker:ALNY]]) has been carving out its position as the leader in RNA interference drug development for years. It entered “peak expectations” in 2006-2007 when scientists won the Nobel Prize for the underlying discoveries, and pharma companies wrote a whole bunch of big checks. Then, everybody realized that small interfering RNA molecules were extraordinarily difficult to deliver where they needed to go inside cells. Alnylam fell into the trough of disillusionment, particularly when its big partner, Roche, walked away. Alnylam had to cut back.
This year, Alnylam showed it was able to deliver siRNA molecules through a convenient subcutaneous injection right under the skin—the kind that’s convenient for patients with chronic diseases. The subcutaneous form was able to knock down more than 80 percent of a disease-related protein called TTR in patients with TTR amyloidosis. Alnylam shares bounced back. Now, it’s true that most RNAi compounds still end up getting metabolized through the liver, making it difficult to deliver to other tissue types. But it was a big step ahead. “I think the Alnylam SC delivery was important along with their transformation into a products based company,” said Houston, the oligonucleotide consultant. “This was the year the RNAi-based therapeutics proved to the world that they are commercially viable for liver diseases. Equally important was Arrowhead R&D’s DPC delivery technology and Hepatitis B program.”
Antisense oligonucleotides for neurology. Carlsbad, CA-based Isis Pharmaceuticals has carried the torch for antisense therapeutics for 25 years, and still has plenty of critics. But Biogen Idec agreed to pay $100 million upfront to Isis this year for its oligonucleotide-based approach against certain neurological conditions, after liking what it saw from this approach to treating spinal muscular atrophy. “If you look at spinal muscular atrophy and a couple preclinical programs, it’s super exciting,” Burke said.
Gene therapy. The idea of using modified viruses to shuttle genes inside cells, to replace missing or faulty genes, burst onto the biomedical scene more than 20 years ago. Cures were on people’s minds, not disease management. Yet, in 1999 Arizona teenager Jesse Gelsinger died in a gene therapy clinical trial, a tragedy that set the field back for years. Netherlands-based UniQure won European approval for a gene therapy in late 2012, but still, we have no FDA-approved gene therapy.
But, but, but. Some scientists never gave up, and this year was the year gene therapy started climbing out of the trough of disillusionment. Cambridge, MA-based Bluebird Bio (NASDAQ: [[ticker:BLUE]]) went public on the strength of gene therapy for rare diseases. That success helped inspire investors to back other new companies like San Francisco-based Audentes Therapeutics and Paris-based GenSight Biologics.
