This newsletter provides commercial insights into the ongoing development of the gene therapy market. The most noteworthy stories appear at the top along with our commentary.
Gene Therapy Expectations for 2018
Last year saw significant regulatory and commercial advancements for gene therapies. While we’re not anticipating any gene therapy drug launches in 2018, the gene therapy team at RxC International believes that 2018 will still be a landmark year for gene therapy’s development as an industry in four particular ways:
- Commercialization: We will continue to see what happens with Luxturna in commercialization, payer models, and efficacy rate. Adoption of Spark’s new payment mechanism for Luxturna’s hefty price tag will be of particular interest.
- Manufacturing and delivery: We expect to see manufacturing and delivery technology continue to evolve, which will be critical for the segment to mature.
- Data: We will begin to see important data releases as products and companies expand their pipelines and reap data from clinical trials. We anticipate gene therapies for hemophilia to be especially important in 2018.
- BD licensing and M&A: Not the focus of this monthly review, but we’ll continue to see deal activity throughout the year.
1. First Reports of Luxturna Being Administered
Jack Hogan, a 13-year old boy from New Jersey, received Luxturna on March 20, becoming the first patient treated with a gene therapy for an inherited disease. Closely following, Creed Pettit, a 9-year old from Florida, received Luxturna on March 21. The first administrations of Luxturna mark a milestone for gene therapy commercial progress, payment models, and innovative contracts.
RxC International continues to watch Luxturna’s commercial strategies and their potential impact on the developing gene therapy market. Read our analysis of Luxturna’s price and market opportunity here.
- Gizmodo: 13-Year-Old Boy Is First Person in US to Receive Newly Approved Gene Therapy for Blindness
- Newsweek: Blind Boy Might Be Able to See Again After New Breakthrough Gene Therapy Surgery
2. Gene Therapy Safety, Efficacy, and Science Still Evolving
Gene therapy is still an emerging segment of healthcare and new findings are potential game-changers. This month, delivery technology advances were on the forefront, along with additional safety concerns.
1. Delivery Technology: New SMRT (Single Molecule, Real-Time) Sequencing technology could improve vector delivery and efficacy by assessing vector quality. The study raises concern that current vector delivery systems are less precise and refined as once believed.
“Some vectors contained less than half the DNA sequence they should have, while genetic errors called chimeras were discovered in other vectors. In a patient, these vectors could have proven ineffective, reducing the likelihood of successful gene therapy outcomes” (potentially requiring higher dosages). SMRT Sequencing analyzes vector quality so companies can improve them, an important step for dose escalation difficulties.
2. Limitations of Safety Study: While dose escalation continues to be a concern for AAV vectors, the recent study published by Dr. James Wilson regarding the safety of gene therapy for SMA contained several “limitations.” One is that the specific vector used may be problematic but not AAV9 vectors in general. Another limitation of Dr. Wilson’s study is that the human version of SMN1 was used in pigs and monkeys, not each species’ native version.
While monitoring the safety of gene therapies is important, it’s equally important for the gene therapy community to continue making progress toward life-saving therapies.
3. Solid Biosciences on Clinical Hold: Safety issues continued to plague Solid Biosciences this month as the FDA put a hold on Solid’s clinical trial for Duchenne muscular dystrophy due to an adverse reaction from the first patient dosed. The FDA’s action is not surprising given Dr. James Wilson’s resignation from Solid’s advisory board and his recently-published article detailing safety issues with the AAV delivery vector Solid is using (see article above, Limitations of Safety Study).
4. CRISPR Redeemed: A paper questioning CRISPR’s safety has been corrected by its original authors who note, in contrast to their original conclusion, that, “Our previous publication suggested CRISPR-Cas9 editing at the zygotic stage might unexpectedly introduce a multitude of subtle but unintended mutations, an interpretation that not surprisingly raised numerous questions.”
- PacBio: Study Demonstrates Potential for SMRT Sequencing to Improve the Safety of Gene Therapy Protocols
- Human Gene Therapy: Severe Toxicity in Nonhuman Primates and Piglets with Systemic High-Dose Administration of Adeno-Associated Virus Serotype 9–Like Vectors: Putting Patients First
- EndPoints: FDA slaps a hold on Solid Bio’s gene therapy for Duchenne MD in wake of safety alert
- BioRXIV: Whole genome sequencing of multiple CRISPR-edited mouse lines suggests no excess mutations
3. Targeted Delivery Continues to Expand: Topical Gene Therapy IND Application Filed
Krystal BioTech’s FDA Investigational New Drug application for a topical gene therapy to treat Dystrophic Epidermolysis Bullosa (DEB) demonstrates more specialization of delivery technology and viral development. We’ve seen gene therapy delivery technology targeting the brain by crossing the blood-brain barrier, the eye (which is easier to target), muscle (which is difficult to target), and now skin.
- GlobeNewswire: Krystal Submits Investigational New Drug (IND) Application for KB103, Topical Gene Therapy Candidate for Dystrophic Epidermolysis Bullosa
4. Gene Therapy Targeted to NASH, Leveraging New Regeneron/Alnylam Partnership
Regeneron Pharmaceuticals has put significant resources behind its Genetics Center that uses genetic information along with electronic health records to identify genes that could play a role in disease. The Center has made several promising finds, with its latest study unearthing a gene variant linked to lower risk for liver disease.
To develop drugs for the discoveries its Genetics Center makes, Regeneron has partnered with Alnylam Pharmaceuticals, the pioneer of RNA interference treatments. Regeneron and Alnylam plan to develop a therapeutic to treat chronic liver diseases such as non-alcoholic steatohepatitis (NASH) by using the genetic information uncovered by Regeneron.
- New England Journal of Medicine: Regeneron Pharmaceuticals Protection from Liver Disease
- BioPharmaDive: Regeneron, Alnylam partner to turn discovery into new drugs for NASH
5. Gene Therapy May Heal Brain
Scientists at UT Southwestern Medical Study have discovered a trigger that may increase the brain’s ability to heal from injury and other conditions. “Turning on” astrocytes (a gene found in brain cells) within mice stimulated the cell’s injury response and resulted in better healing. Turning off or deleting the gene resulted in larger injuries and longer healing times. This discovery may one day lead to gene therapies to treat spinal cord injuries, concussions, stroke-induced damage, and other brain-related injuries.
- Science Daily: Gene therapy may help brain heal from stroke, other injuries
About RxC International
Understanding the subtleties of gene therapies is critical for bringing these treatments to market. RxC International has extensive experience successfully commercializing and launching new drug products, developing innovative solutions, realizing a product's best potential, and working across organizations to achieve common goals.
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