The field of gene modifying is moving fast. In late October, two new documents described technologies that allow for the precise editing of individual DNA bases ? an A to a T, the C to a G? and, separately, a mechanism regarding genetically editing RNA . Both have been heralded as main advances.
But let’ s back up a bit from the cutting edge tools to the actual application: How is gene editing progressing, in terms of biotech pipelines, investment, and therapeutic approvals?
In its recent report, titled Gene Editing: The Next Breakthrough within Regenerative Medicine , Informa Pharma Cleverness answers those questions with a focus on three major current technologies: CRISPR/Cas9, zinc-finger nucleases (ZFNs), and transcription activator-like effector nucleases (TALENs). All three tools allow researchers to permanently modify an organism’ s genome , without introducing foreign DNA.
CRISPR/Cas9 has by far attracted the most hype and investment dollars. According to Informa’ s research, near to three-quarters (74 percent) of gene editing programs at this point use the technique. This, despite the drawn-out patent dispute and the fact that it was harnessed for human genome editing less than 5 years ago . Even with this dominance, the particular discovery might quickly become dated, noted Amanda Micklus, principal analyst for Informa Pharma Intelligence.
“ I don’ t even think CRISPR/Cas9 is going to be the particular end-all, ” Micklus said in a phone interview. “ I think that once we move forward, as more discoveries are made, there’ s going to become more tools added to the gene editing toolbox and we’ ll have to see how some of these candidates play out. ”
It would also be early to write-off ZFNs and TALENs, she said . Both technologies have reached human trials, the milestone that nothing of the CRISPR/Cas9 companies have yet achieved.
In terms of investment, all 3 technologies received backing from Big Pharma between this year and 2017, the report highlights. Four of those offers were estimated to be worth more than $1 billion (the financials behind several others were undisclosed).
Pfizer tops the list with its 2014 Cellectis partnership, that could be worth as much as $3 billion . Servier partnered along with Cellectis the same year, in a deal valued at just more than $1 billion. In 2015, Vertex closed a $2. 6 billion agreement with CRISPR Therapeutics and Shire (working through Baxalta) signed a $1. 7 billion dollars CAR-T deal with Precision Biosciences in 2016.
When it comes to repeat business, Novartis committed to three gene editing companies during that five-year window. AstraZeneca and Shire also independently penned two separate gene editing agreements.
Whilst all of the deals could be characterized as early stage, Sangamo Therapeutics and Cellectis have moved their respective systems into the clinic.
With all the intellectual property underpinning ZFN technology, Sangamo Therapeutics has initiated a robust pipeline, targeting diseases which range from HIV/AIDs to hemophilia A and B. According to the survey, five of these candidates progressed into Phase 2 medical trials. The Richmond, California-based biotech has also entered into contracts with Biogen, Shire, and the CHDI Foundation to co-develop or out-license the technology.
Meanwhile, Cellectis appears to be the ruler of TALEN editing. The decades-old French biotech initial licensed the technology in 2012 from Iowa State University or college. It is now one of the leaders in this field, attracting partnerships along with Pfizer and Servier for its work in oncology. Specifically, it’ s developing so-called chimeric antigen receptor T-cell (CAR-T) therapies, a key component of CAR-T cell immunotherapies . It has one particular program in Phase 1 clinical trials.
For CRISPR/Cas9, Intellia Therapeutics could be the first to submit an investigational new drug software in the U. S., the authors note, becoming the first in line to begin human trials. Editas Medicine is close behind , having bumped back its timeline for initial human testing from 2017 to 2018. In vivo work has been done by research institutes in the United States plus China, building knowledge in this area while also raising numerous ethical questions.
Whilst an FDA approval is clearly still years aside, the issue of pricing is definitely on the horizon.
“ It’ s going to be a really tough issue for payers to be able to handle these very high priced gene therapies, specifically as patients often change insurance companies and move through plan-to-plan. Who’ s going to be responsible for those costs? ” Micklus declared.
Probably the model for a gene-editing launch will come through its close up relative, gene therapy. FDA is expected to follow the suggestion of its advisory committee and approve Spark Therapeutics ’ Luxurna. The novel gene therapy targets a rare condition known as RPE65-mediated passed down retinal disease. Experts expect it to be priced more than $500, 000. Some analysts are even predicting the $1 million price tag , in line with the first-ever gene therapy approved within Europe, known as Glybera .
“ A lot of these therapies are going to be one-time therapies, so you need to think about how they are paid for, ” Micklus stated. “ Are they going to be paid upfront? Are they going to end up being paid over time? And also, are they going to be paid depending upon how well a patient responds to those therapies? ”
Gene editing may be an exciting new frontier, but it’ s going to run into some familiar walls.
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