Gene therapy

Monthly Gene Therapy Business Review - Special Issue

RxC International Gene Therapy Business Review Special June Edition.png

BIO International Convention, Boston MA, June 4-7, 2018

BIO is back in Boston to celebrate 25 years of innovation.  RxC International's Rich Tinsley and Jim Hoyes will be in attendance.  We hope to meet you there. It's a beautiful time of year in Boston, MA.

This year's conference is sure to be appealing to the gene therapy community for a host of reasons.  We identified more than 20 different sessions dedicated to gene therapy with over 300 attending organizations focused on gene therapy. Given individual time constraints and tight schedules please find a few gene therapy session recommendations. Note the dates and times, unfortunately there is some overlap between sessions so please prioritize. 

1) Gene Therapy Regulation

US Cell & Gene Therapy Regulatory Policy Update 

Tuesday 1:45 PM 2:45 PM in Regulatory Innovation Room 207, Level 2

Speakers: * Wilson Bryan, Director, Office of Compliance and Biologics Quality Center for Biologics Evaluation and Research at FDA * Manal Morsy MD,PhD,MBA, Senior Vice President, Head of Regulatory Affairs at Athersys, Inc * Anne-Virginie Eggimann, MSc, Vice President, Regulatory Science at bluebird bio, Inc. * Dr. Snehal Naik, PhD Associate Director, Global Regulatory Affairs at J&J * Dr. Melody Eble, PharmD, Director, Global Regulatory Affairs at J&J

Recent or planned updates to the regulatory framework for cell and gene therapy products and experience with the new RMAT (Regenerative Medicine Therapy Designation) will be reviewed and discussed.

Advancements and regulatory framework in human genome editingWednesday 4:15 PM 5:15 PM in Genome Editing Room 210B, Level 2

Speakers: * Carrie Wolinetz PhD, Acting Chief of Staff and Associate Director, Science Policy at National Institutes of Health * Dr. Jakob Reiser, Office of Tissues and Advanced Therapies Division of Cellular and Gene Therapies at FDA/CBER * Sandy Macrae, MB, PhD, CEO at Sangamo Therapeutics * Gideon Rose, Editor at Foreign Affairs

Human genome editing is an exciting technology making history by leveraging advanced science to bring forward new classes of innovative medicines to patients. We have seen many breakthroughs in recent times, and significant advancements in the development of genome editing treatments for patients. With this advancement, we have seen a heightened interest from around the globe in ways we can use responsibly genome editing technology to improve human health. This session will tackle the regulatory frameworks for therapies that make use of genome editing. A panel of distinguished experts will share their perspectives on navigating these regulatory requirements.

2) Gene Therapy Commercialization

Delivering on the Promise of Gene Therapy

Tuesday 2:30 PM 3:45 PM in Room 253ABC, Level 2

Speakers: * Michael Dombeck, Vice President, Business Development at Precision Biosciences * Alison Finger, Chief Commercial Officer at bluebird bio, Inc * John Pieracci PhD, Director, Gene Therapy Process Development at Biogen Corporation  * Bob Smith Senior Vice President, Global Gene Therapy Business at Pfizer, Inc. * Sandy Macrae MB, PhD, CEO at Sangamo Therapeutics * Steve Bagshaw, CEO at FUJIFILM Diosynth Biotechnologies

Gene therapies are transforming patients' lives in ways that were unimaginable twenty years ago. With recent scientific advances interest in the ways that gene therapy can improve human health are exploding, with the potential to treat and cure disease. With these advances come challenges and opportunities in scientific discovery and new approaches in delivering drugs. Panelists will tackle these issues and share what it takes to bring new types of medicines to patients.

Advances in Genome Editing - The Next Frontier in Human Health 

Wednesday 1:45 PM 2:45 PM in Genome Editing Room 210B, Level 2

Speakers: * Samarth Kulkarni, Ph,D CEO at Crispr Therapeutics * Lakiea Bailey Executive Director, WWBD at Sickle Cell Community Consortium * Ms. Katrine Bosley, CEO at Editas Medicine * Mike Certo, PhD, Head, Genome Editing at bluebird bio, Inc. 

There are thousands of genetic diseases for which there is no treatment. Genome editing is a groundbreaking technology which offers a solution for the development of therapies for said diseases. Scientific advances in human genome editing have proven that somatic cell genome editing has the potential to treat and cure genetic diseases for which there is no cure. Leading experts in the field of genome editing will discuss the most recent breakthroughs and the dynamic opportunities on the horizon.

Making Genetic Therapies a Reality for Patients 

Wednesday 4:15 PM 5:15 PM in Orphan & Rare Diseases Room 209, Level 2

Speakers: * David Williams, Chief Scientific Officer and Senior Vice President for Research at Boston Choldren's Hospital * Dr. Emmanuel Dulac, Chief Commercial Officer at Alnylam Pharmaceuticals * Jeffrey Walsh, Chief Financial and Strategy Officer at bluebird bio, Inc. * Dr. Kathy High PhD, President and Head of R&D at Spark Therapeutics * Sam Rasty PhD, Chief Operating Officer at Homology Medicines, Inc. 

Gene-based therapies are increasingly being sought for patients in part due to advanced technologies that can regulate, edit or correct genetic components. As these approaches are relatively new to drug development and even newer to treating patients, many questions still exist beyond scientific translation from the lab to the clinic. Attendees will have the opportunity to hear from a panel of experts as they discuss the importance of commercial, scientific and clinical working together, every step of the way, from development to commercialization, to bring a new treatment to patients.

3) Public Private Partnership

The Changing Face of Academic Technology Transfer 

Tuesday 4:15 PM 5:15 PM in Translational Research Room 206AB, Level 2

Speakers: * Howard Fillit, MD, Founding Executive Director and Chief Science Officer at The Alzheimer's Drug Discovery Foundation * Rubén D. Flores-Saaib, PhD, Dorector of Commercialization at UCSD * Wendi Yagnik PhD, Global Head of Academic Partnerships and External Innovation at Novartis Institutes for BioMedical Research, NIBR * Dr. Sadhana Chitale MBA,PhD, Director of Life Sciences/Technology Transfer at Office of Industrial Liaison at NYU  

With support and recognition from senior leadership, academic institutions are revamping how they conduct technology transfer and lowering barriers for the movement of new technologies to the market. Technology Transfer offices (TTOs) are willing to commit their own resources and put skin in the game to create more robust early stage assets especially in the area of drug development. Many TTOs now work much early in the process with their partners from biotech, pharma and foundations to raise non-dilutive capital and validate assets. In this session you will hear from representatives of leading academic institution, disease foundation, pharma and biotech on how working with TTOs has been a win-win for both sides.

4) Pricing, Access & Value-Based Payments

Developing a Path to Value-Based Payment for Transformative TherapiesTuesday 11:00 AM 12:00 PM in Patient Access & Reimbursement Room 210A, Level 2

Speakers: * Paul Levesque, Global PResident, Rare Disease at Pfizer * Marianne Hamilton, Research Director at Duke-Robert J. Margolis, MD, Center for Health Policy * Dr. Michael Sherman, Chief Medical Officer & Senior Vice President, Health Services at Harvard Pilgrim Healthcare * Ms. Katrine Bosley CEO at Editas Medicine, Inc. * Dr. Gregory Daniel, Deputy Director and Clinical Professor at Duke-Robert J. Margolis MD, Center for Health Policy, Duke University

Value-based payment (VBP) arrangements, which align payments to observed value and outcome in a population, can be critical tools to improve patient outcomes and lower overall healthcare costs. VBP creates a unique approach to financing curative or transformative therapies, which are highly effective but could also impose considerable costs and uncertainties on the U.S. healthcare system. Specifically, this panel will focus on special issues in applying VBP arrangements in the transformative therapy space, with a focus on distinct issues in "single administration" therapies, distinctive barriers to implementing new payment models within the single-administration therapy context, design elements of new payment models to address these needs and identify system, policy, and cultural changes needed to facilitate new payment models in this context.

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.

If you would like to subscribe to receive RxC International’s Monthly Gene Therapy Business Review, sign up here.

Monthly Gene Therapy Business Review - March 2018

RxC International Gene Therapy Business Review March 2018

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:

  1. 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.

  2. Manufacturing and delivery: We expect to see manufacturing and delivery technology continue to evolve, which will be critical for the segment to mature.

  3. 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.

  4. 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.

  1. Gizmodo: 13-Year-Old Boy Is First Person in US to Receive Newly Approved Gene Therapy for Blindness

  2. 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.”

Reference Articles

  1. PacBio: Study Demonstrates Potential for SMRT Sequencing to Improve the Safety of Gene Therapy Protocols

  2. 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

  3. EndPoints: FDA slaps a hold on Solid Bio’s gene therapy for Duchenne MD in wake of safety alert

  4. 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.   

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.

  1. New England Journal of Medicine: Regeneron Pharmaceuticals Protection from Liver Disease

  2. 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.

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.

If you would like to subscribe to receive RxC International’s Monthly Gene Therapy Business Review, sign up here.

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Landmark Month Sees Second Gene Therapy Approved and Other Wins

RxC International Gene Therapy Newsletter

October was a landmark month for gene therapies with the approval of the second-ever gene therapy in the US, Yescarta (axicabtagene ciloleucel) from Kite and Gilead.  The prior approval of Novartis’ Kymriah is more proof that gene therapies are set to shake up the pharma industry.  Gene therapies saw other wins as Luxturna, Spark’s treatment for Leber congenital amaurosis, received the FDA’s recommendation for approval and Bluebird Bio’s interim data report for its gene therapy Lenti-D to treat cerebral adrenoleukodystrophy showed promising results.

That’s not to say it was all smooth sailing.  Pricing remains forefront in the discussion of gene therapies’ value and potential to “break the bank.”  And not all therapies are succeeding as Alnylam suspended its RNAi fitursiran trial after a patient death.

RxC International will continue to closely monitor gene therapy developments to provide readers with news and insights into this ever-evolving market.


Pricing Debate Intensifies with Approval of First Gene Therapies

The recent approvals of the first two gene therapies in the United States have intensified the debates over pricing and the financial burden these treatments may have on the healthcare system.

While gene therapies are emerging onto the commercial market, the debate surrounding affordability is not new.  Dating back to the era of Lipitor and other blockbuster PCP-driven drugs to the expansion of the oncology market to the more recent emergence of multiple rare disease treatments, the question has always been the same: “How can we afford them?”  The real question, however, is not whether we a society can afford gene therapy treatments, but whether we can afford not to pursue treatments that extend or improve people’s lives.


Gene Therapy Pricing and Target Patient Population


The article offers some important insight into the pricing debate, but at the same time makes the fundamental mistake of grouping all gene therapies into a single category.  Gene therapies are far from a homogeneous group so must be thoughtfully segmented to fully understand the different dynamics at play for each product.

The chart seems to purport an overall correlation between pricing and target patient population, however it doesn’t take into account the basic HEOR measure of cost per year of life saved.  While gene therapies targeting rare diseases may have a smaller patient pools, they often target childhood diseases with the potential to add decades to each patient’s life. Oncology is a very different dynamic.


Harvard Scientists Reveal New Gene Editor

Using CRISPR-Cas9 technology, scientists can now change a single DNA letter.  This advancement expands the capabilities of the first base editor, created last year, by converting additional bases.

While CRISPR continues to make strides for gene therapy advancement, it is still a long way from creating commercial therapies.


Research Updates

Second Gene Therapy Treatment Approved

The October 18th approval of Yescarta (axicabtagene ciloleucel), a CAR-T treatment for adults with relapsed or refractory large B-cell lymphoma, places Kite and Gilead in the new market of approved US gene therapies. Novartis’ Kymriah, the first gene therapy to gain approval in the US, is also a CAR-T therapy.  While currently aimed at different oncology segments, the two CAR-T treatments could become competitors as both brands seek to expand product labels. 


Fitusiran's Recent Failure Opens Door for Additional Therapies

The September suspension of trials for RNAi fitursiran following the death of a patient in one of the studies has opened the door for two competing gene therapies that offer long-term benefit from one administration.


Gene Therapy Receives Unanimous Recommendation for Approval

Luxturna, a treatment for a hereditary form of blindness, received recommendation for approval from an FDA advisory committee.  Spark Therapeutics, the treatment’s developer, is expected to receive a decision from the FDA by January.


Encouraging Results for Gene Therapy Treatment of Fatal Neurodegenerative Disease

Interim data for Bluebird Bio’s gene therapy treatment Lenti-D for boys suffering from cerebral adrenoleukodystrophy (CALD) showed encouraging results.  Of the 17 boys who received treatment as part of Bluebird’s trial, 15 were alive and stable after 24 months. "The clinical experience with Lenti-D demonstrates the potential for gene therapy to benefit patients with CALD," said David Davidson, MD, chief medical officer of Bluebird Bio.  The company is currently considering its plans for FDA approval.

About RxC International

Understanding the subtleties of the 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.

To receive updates from RxC International, follow us on LinkedIn. Visit our Gene Therapy Resource Center for other posts and resources on launching and commercializing gene therapies.

About the Author

Richard Tinsley is a Strategy Partner at RxC International with over 20 years of life sciences consulting experience. He is a recognized leader in strategy, commercialization, life cycle management, and sophisticated forecast modeling. Rich has deep expertise in specialty markets such as rare diseases, HIV, oncology, neurology, and diagnostics.

Gene Therapies: Pathways for Commercial Success

RxC Gene Therapy Pathways for Commercial Success

Gene therapies are poised to enter the US healthcare system within the next 1-2 years as viable treatment options for a variety of diseases. In response to this burgeoning opportunity, the Institute for Clinical and Economic Review (ICER) convened a policy summit and recently released a report on the potential value and challenges of gene therapy treatments, GENE THERAPY: Understanding the Science, Assessing the Evidence, and Paying for Value.

Developing Pathways for Commercial Success

The pathway to commercial success is just as vital as the pathway to regulatory approval. RxC International has drawn key insights in conversation with ICER’s white paper for the commercial entrance of gene therapies.

Value Assessment for Gene Therapies:  Pricing and innovative payment mechanisms have received much attention as significant concerns for gene therapy stakeholders. A more pressing issue, however, is that gene therapies will not have the robust data generated by clinical trials. The reliance on abbreviated data sets coupled with the fact that gene therapies are not a homogenous group mean that market sizes, target populations and clinical trial evidence will vary greatly.  Thus, the plan for gene therapy commercial success must be integrated with the clinical development strategy. At RxC we have modified the typical Target Product Profile into the Target Value Profile that better reflects the market dynamics of gene therapies.

Identifying partners and alliances for commercialization: Due to the complexity of gene therapy commercialization, persuading providers to use gene therapy treatments may require the resources of a partner with commercial expertise. To assist companies in identifying partners and alliances, RxC has the experience and models for forging the strategic partnerships necessary for commercial success.

RxC International Advantage

RxC International, a premier life sciences consulting firm, has created proprietary, cross-functional frameworks for aiding life sciences companies with commercialization and go-to-market strategies for new treatments.  We have adapted our models to assist clients with navigating the unchartered waters of planning and commercializing gene therapies. If you are interested in keeping abreast of our expert work in the gene therapy market, please follow RxC International on Linkedin for updates.