Monthly Gene Therapy Business Review - Special Issue

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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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Monthly Gene Therapy Business Review - February 2018

Monthly Gene Therapy Business Review - February 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.

Top Stories:

  1. Lessons Learned from Hepatitis C: Intense Competition Requires Careful Commercial Planning for Sickle Cell Gene Therapies
  2. Gene Therapy IP, Manufacturing, and Delivery Pathways Still Evolving
  3. FDA Moving Forward with its Role in Advancing a Modern Framework for Gene Therapy

Monthly Gene Therapy Business Review - January 2018

GT Jan NL graphic.jpg

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.

1) Still Learning What We Don’t Know: Gene Therapy Market Impacted by Safety Concerns

Extreme market response to postulated gene therapy immunity and the unsettling results of research just made public by an industry pioneer remind us that the gene therapy market is still in its infancy.  We still don’t know what we don’t know, particularly when it comes to long-term outcomes and adverse events.  Inherent risk and unknowns affect both how and how quickly early therapies will be adopted and with which patients.  Effective patient segmentation and communication are key and shouldn’t be underestimated even with successful clinical results.

Two unrelated reports emerged this month questioning the safety of gene therapy treatments, one of which sent Intellia, Editas, and CRISPR stocks tumbling $500 million (temporarily).  This extreme reaction to the news that many people could be immune to CRISPR-Cas9 technology demonstrates the immaturity of the gene therapy market and how much we still don’t know.

Another report, authored by Dr. James Wilson, revealed that nerve and liver damage occurred in animals who received gene therapy treatment for SMA.  Humans have responded well to gene therapy for SMA but Dr. Wilson’s caution to carefully monitor subjects underscores the fact that we still don’t know the long-term effects of gene therapy treatment or the potential result of overdosing.

One possible solution to safety concerns comes from an unexpected source: Microsoft.  The company has developed a new tool, Elevation, that uses artificial intelligence to predict off-target effects. This tool may identify patients who would respond optimally to certain gene therapies and track patients and treatment reactions over time.

  1. BioRxiv: Identification of Pre-Existing Adaptive Immunity to Cas9 Proteins in Humans
  2. Human Gene Therapy: Severe toxicity in nonhuman primates and piglets following high‐dose intravenous administration of an AAV vector expressing human
  3. Nature: Prediction of off-target activities for the end-to-end design of CRISPR guide RNAs
  4. Genetic Engineering and Biotech News: FDA Imposes Clinical Hold on Bellicum Lead Candidate BPX-501

2) Headline “Gene Therapy Could Make Cancer Care More Unequal” Probably Not True

A recent article in MIT Technology Review used that headline to grab attention, but we maintain that gene therapy is not more unequal than other types of treatments for rare diseases, especially when other therapies cost $475,000 and many patients already travel to leading cancer centers for treatment. Access to care in the US is a system problem, not just a gene therapy problem.

Due to the cost and required expertise for effective treatment, most companies commercializing gene therapies will rely on a “centers of excellence” distribution model. An interactive map in the article demonstrates the treatment sites for Kymriah and Yescarta.

MIT Kymriah Map.jpg

In rolling out Kymriah, Novartis underscored its achievement developing a “reproducible product” after manufacturing CAR-T cells for more than 250 patients from 11 countries.  This is proof that centralized manufacturing can work for gene therapy treatments. 

  1. MIT Tech Review: Gene Therapy Could Make Cancer Care More Unequal, and This Map Shows Why
  2. Genetic Engineering and Biotech News: Cell Therapy Manufacturing: All Signs Point to Commercialization

3) China’s Quest for Gene Therapy Success

Three news articles emerged this month that paint a picture of aggressive Chinese development of gene therapy treatments and technologies.  A shorter regulatory process along with willingness to skirt potential ethical issues have made China a gene therapy hotspot.  While it is unlikely that gene therapy developers in the United States will face future commercial challenges from China, the speed with which China is advancing gene therapy will be important to monitor.

  1. The Wall Street Journal: China, Unhampered by Rules, Races Ahead in Gene-Editing Trials
  2. The Wall Street Journal: China Breaks a Cloning Barrier: Primates
  3. Washington Post: Targeting Biotech’s 1%, China Speeds Into Gene Therapy

4) Answering ICER: Spark CEO Offers Rationale for Luxturna Price

This case serves as a good reminder that gene therapy stakeholders—especially developers, investors, and payers—should adopt a broad perspective as the way we value therapies continues to evolve.

Institute for Clinical and Economic Review (ICER) did not surprise anyone with their updated report on Spark Therapeutics’ $850k price tag for Luxturna, revealed before #JPMorgan18.  In its report, ICER concludes that Luxturna should be priced 75-82% less to be cost effective for a 15-year-old patient, the average patient age in Spark’s clinical trials.  The report also noted that when accounting for all savings from indirect “societal benefits,” Luxturna should be priced 50-57% less.

Spark CEO Jeff Marrazzo’s interview with Xconomy provides insight into what factors the company used to determine Luxturna’s value and to price accordingly.

  • Thinking short term: “We didn’t necessarily grab all of the value, and we went above what payers were positioning as affordability. But we came in to a point where, most importantly, I believe we can drive access for patients.”
  • Using non-traditional economic measures: “There were about 25 court cases in states that release award information for people who either partially or fully lost their sight. The awards were $250,000 on the low end and $4 million on the high end of those cases, with an average at about the $1 million mark ... I think that’s helpful in showing how our society values sight.”
  • Thinking long term: “I feel a certain responsibility to make sure we have commercial success, but I also felt we should do it in a way I think the world should look at in the future … when you start talking about hemophilia, Pompe disease, AveXis with their [spinal muscular atrophy] product, which may be replacing a chronic drug in nusinersen (Spinraza), there are cost offsets. In one of our hemophilia trials, we had 10 patients that take, on average, $406,000 per year of [blood-clotting factor replacement drugs].”
  1. ICER: Institute for Clinical and Economic Review Report on Voretigene Neparvovec Suggests Substantial Price Discount Needed to Meet Traditional Cost-Effectiveness Standards
  2. Xconomy: Spark CEO Marrazzo on Gene Therapy Pricing & Paving the Way for the Field

News and Updates


  1. Globe Newswire:  Spark Therapeutics Enters into a Licensing and Supply Agreement for Investigational Voretigene Neparvovec Outside the U.S. with Novartis

 CAR-T Updates

  1. US News: Could Gene Therapy Someday Eliminate HIV? (see also PLOS Pathogens: Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS)
  2. Genetic Engineering and Biotech News: Kite Earns Patent for Method to Increase Efficacy of CAR-T
  3. Globe Newswire: Sorrento Therapeutics to Present Potential “Game-Changer” Non-Viral CAR-T Tec hnology for Autologous and Allogeneic (off-the-shelf) CAR-T Therapies

CRISPR Updates

  1. MIT Tech Review: U.S. Doctors Plan to Treat Cancer Patients Using CRISPR
  2. G enetic Engineering and Biotech News: Nonviral Gene Therapy Platform Delivers CRISPR/Cas9 to Tumors

Funding, Launch, and Partnership News

  1. Business Wire: Kite Announces Clinical Collaboration to Evaluate Investigational Combination of Yescarta™ (Axicabtagene Ciloleucel) and Pfizer’s Utomilumab in Large B-Cell Lymphoma
  2. BioSpace: REGENXBIO Banks on Strong Gene Therapy Pipeline and Potential Partnerships
  3. Genetic Engineering and Biotech News: Sangamo, Pfizer Partner on Gene Therapy for ALS, FTLD

Clinical Stage Research Updates

  1. Singularity Hub: IONIS antisense drug advancing in Huntington’s Disease after Phase 1/2a study success

Pre-Clinical Stage Research Updates

  1. NIH: NCATS’ Pre-Clinical Collaboration Enables Gene Therapy for Rare Muscle Disease to Advance to Clinical Trial
  2. Nature: Targeted repair of heart injury by stem cells fused with platelet nanovesicles
  3. Fierce BioTech: Atlas-backed Generation Bio promises ‘druglike’ gene therapy
  4. Medical News Today: Diabetes: Can gene therapy normalize blood glucose levels?

 Interesting News

  1. MIT Tech Review: Meet the Woman Using CRISPR to Breed All-Male “Terminator Cattle”
  2. Oregon Live: Climate change might kill off chocolate by 2050, so scientists turn to CRISPR gene-editing technology

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About RxC International

RxC International is a premier life sciences management consulting firm. RxC collaborates with clients to identify and develop growth opportunities. The firm leverages consulting partners and advisers to combine strategic and operational expertise to bring multiple perspectives to every engagement. The firm has deep expertise in corporate strategy, new product strategy, and commercial excellence. 

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