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.

RxC International to Attend BIO International Convention 2018

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RxC International partners Jim Hoyes and Rich Tinsley will attend this year’s BIO conference in Boston, June 4-7, 2018. We are excited to have the opportunity to reconnect with our existing client base and make new connections. Please message us to set up a time to meet and discuss our current strategy consulting work in areas like portfolio optimization, life cycle managementgene therapy, launch readiness, and co-promotional partnerships.

#BIO2018, #MakingBIOHistory, #bioconvention

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

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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

Global

  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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A little earlier than expected, Spark’s announces Luxturna pricing, $850k

Spark surprised us with the early announcement of Luxturna’s $850,000 price tag, a week prior to #JPM18 when we expected it.

The company has clearly done their homework and is doing a very good job of leading the gene therapy market in the right direction – kudos to their team.

Below is a summary of what you need to know about the Luxturna clinical story and its market opportunity. We’ve also highlighted some of the questions regarding this highly watched commercial launch.

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Market Opportunity Observations

  1. Statistical Significance vs Clinical Significance vs Value: Spark has pretty clearly demonstrated the statistical significance of Luxturna.  However, the true measure of Luxturna’s commercial success will be driven by the clinically meaningful or practical significance the treatment brings in patients’ lives.  Luxturna is not a cure for blindness, but has shown improvement on a unique and practical study endpoint that needs to translate into patients’ lives to create meaningful value.  As noted below, the direct and indirect costs of low vision/blindness are surprisingly low at $17-27k per person per year (at least in our opinion). Without trying to make a direct comparison of the seriousness or importance of either condition, the urinary incontinence market provides a good example of the clinical versus statistical issue. One very commercially successful drug showed a statistically significant drop in urge incontinent episodes from 3.7/day to 1.4/day, a 60% reduction.  While this was a meaningful difference, patients still required planning and coping strategies to prepare for those remaining 1.4 episodes. The drug cost $2k-$3k/year.  For Luxturna, though vision may be partially restored, patients may need to rely upon current means of managing vision loss.  How does this continued reliance align with the $850k cost?
  2. Patient Segmentation and Prioritization: Needless to say, the above speaks to the importance of knowing who is likely to benefit and by how much. 
  3. Understanding the Forecast: We’ve provided an external consensus Luxturna forecast below although it is hard to know what the key drivers of Luxturna uptake are: is it the need for real world clinical experience/proven value, is it patient selection, is it payer access, is it innovative over time revenue recognition, is the company managing expectations, or likely a complex mixture of all of the above? It seems a little slow, but to truly grasp this new emerging market for expensive “one and done” therapies we need to understand the Patient Flow Dynamic adapted for the gene therapy market.  Gene therapies, properly forecasted, will have very different revenue curves than traditional markets – this forecast looks a little too traditional.
  4. Market Access: Spark’s contracts and payment models may offer a way forward for future gene therapies.  How the marketplace reacts (i.e. potentially and ironically delaying treatment) waiting for the CMS decision to their delayed payment proposal remains to be seen.

Efficacy

  • Spark created and validated its own clinical endpoint: Multi-Luminance Mobility Test (MLMT).  MLMT assesses participants’ ability to navigate a course at seven different levels of illumination.  It encompasses aspects of visual field, visual acuity, light perception and contrast sensitivity. The MLMT is a grid of arrows which a participant must follow, stepping over and around obstacles to reach a door at the end.
  • Luxturna Phase 3 clinical study results showed a statistically significant difference between the intervention group (n=21) and control participants (n=10) at one year in mean bilateral MLMT score change although it does appear to have some variability in response based on the confidence interval (mean difference of 1.6; 95% CI, 0.72, 2.41), but it is a small sample. 93 percent (27 of 29) of all treated Phase 3 trial participants saw a gain of functional vision as assessed by bilateral MLMT.  Furthermore, the mean MLMT improvement was sustained at 3 years (1.8 lux levels at three years, compared to 1.9 lux levels at one year).
  • No serious adverse events (SAEs) associated with Luxturna or deleterious immune responses have been observed. Two ocular SAEs were reported in the clinical program: one in Phase 1 (the treatment for bacterial endophthalmitis led to elevated intraocular pressure and subsequent optic atrophy) and one in Phase 3 where the SAE was related to the surgical procedure and resulted in foveal thinning and a sustained reduction in visual acuity (VA) in one participant.

Market Opportunity

Worldwide prevalence is 6,000 individuals with biallelic RPE65 mutations (1,000-2,000 people in the U.S.), although not all patients are candidates for Luxturna.

Luxturna_Forecast (1).jpg

Assuming no price inflation and full $850k price, the cumulative global sales are $2.4 billion and represent 2,800+ treated patients. More realistically, these forecasts probably assume treatment of 3,000-4,000 patients with rebates and discounts around the world.

Contracting and Access

At launch, Spark is offering two contracting alternatives:

  1. An outcomes-based rebate arrangement with a long-term durability measure: Spark Therapeutics will share risk by paying rebates if patient outcomes fail to meet specified thresholds for both short-term efficacy (30-90 days) and longer-term durability (30 months) measures.
  2. An innovative contracting mode under which the payer or payer’s specialty pharmacy will purchase Luxturna, agree to provide coverage for its members consistent with the product label, expedite benefits processing and cap patient out-of-pocket amounts at in-network limits.

Spark Therapeutics is seeking additional solutions to allow customers to pay for LUXTURNA in installments over several years.  Currently, government price reporting requirements make such solutions infeasible. Offering outcomes-based rebates above a certain threshold may also provide government price hurdles. Spark CEO Jeffrey D. Marrazzo has said, “We are committed to finding a novel solution to providing an installment payment option to payers” and are “eager to work with CMS to enable more meaningful rebates as part of the pay-for-performance model.”

Interesting HEOR Fact

According to a 2013 evaluation of the Economic Burden of Vision Loss completed by NORC at the University of Chicago, the direct and indirect costs of low vision is $15,900 per person with vision loss. It turns out to be very difficult to allocate costs between those who are blind versus those with impairment, but the study conservatively estimated that low vision costs are $26,900 per year for each person blind.

Another great resource to delve into the HEOR and other market dynamics can be found in the draft ICER report released in November 2017 (link to document below).

RxC International will continue to monitor the market implications of Luxturna’s price as well as other gene therapies as they are approved.

Connect with Us at #JPM18

RxC International will be at the JP Morgan conference and surrounding events.  To schedule 20 minutes discussing gene therapy commercialization and access issues, contact us here.

References

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.

Visit our Gene Therapy Resource Center to sign up for our monthly newsletter or to explore other posts and resources on launching and commercializing gene therapies

Monthly Gene Therapy Business Review - December 2017

RxC onthly Gene Therapy Business Review - December 2017

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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.

Connect with Us at #JPM18

RxC International will be at the JP Morgan conference and surrounding events.  To schedule 20 minutes discussing gene therapy commercialization and access issues, contact us here.

We are expecting a few gene therapy points of interest to emerge from JMP 2018, including:

  • Pricing discussions
  • Regulatory Approval issues and timing
  • Commercialization challenges and market access strategies

1) First Mover Advantage? Gilead Blazes Trail for Competition

While having the first-mover advantage is traditionally considered a boon in the pharmaceutical industry, in Yescarta’s case, any advantage is disappearing with delays in access as Gilead builds reimbursement infrastructure that benefits the competition and allows increased time for competitors to launch.

Conservative Wall Street uptake forecasts that revenues would exceed $9 million in 2017, the equivalent of treating roughly 25 patients, weren’t met.  Gilead is a highly capable commercial organization that has faced access and pricing challenges before but this case demonstrates the importance of careful commercial planning when developing high cost gene therapies both for realizing returns on investments and ensuring that patients who desperately need these treatments receive them in time to make a difference.

Hundreds of cancer patients sit on waiting lists to receive Yescarta but only 5 have been treated since this potentially life-saving gene therapy’s approval in October. The new treatment has no billing code for Medicare/Medicaid recipients, forcing hospitals to choose between leaving dying patients untreated or risking millions of dollars that may not be reimbursed.  Insurance companies have also been slow to adopt the treatment.

 2) Newly-Published Yescarta Study Raises Safety Concerns

Gene therapy companies must develop a distribution model that addresses safety concerns while supporting commercialization efforts.  Since many gene therapy products could require specialized capabilities, treatment centers of excellence are likely to be an important element to commercial planning.

A study published this month in the New England Journal of Medicine highlights the success of Yescarta (axicabtagene ciloleucel) in treating diffuse large B-cell lymphoma but also reveals that 95% of those who received Yescarta experienced severe effects and that 13% of those side effects were classified as life-threatening.  The FDA’s approval of Yescarta included a risk evaluation and mitigation strategy (REMS) that requires hospitals and staff to be specially certified to dispense or administer Yescarta.

While safety needs demand additional research, the study indicated that even after 15 months 42% of patients who received Yescarta are still responding to treatment.

3) Results from Hemophilia Gene Therapy Studies Prompt Pricing Questions...Again

While certainly to be priced extremely high, a gene therapy that cures Hemophilia offers significant savings over the lifetime of a hemophilia sufferer given that hemophilia patients require lifelong treatments that on average cost $155,136, but a patient using inhibitors can cost $400,000+ a year.

Pricing a cure for Hemophilia raises the question of if there’s a maximum that health systems are willing to pay for a treatment. Depending on assumptions, the present value of a lifetime worth of therapy can easily exceed $3 million and be as high as $7 million. How much is a cure worth for a patient? Should therapy cost differ based on patient age?

The absence of long-term data throws another wrench into pricing considerations. Without information on the longevity of a Hemophilia gene therapy, payers won’t even know if treatments truly are lifelong.

One important aspect of commercializing a Hemophilia cure, no matter what the final price might be, is communicating its value to stakeholders and ensuring that there is transparency around pricing.

The recent success of two Hemophilia studies offers hope to patients who undergo frequent infusions.  Results from BioMarin’s study for a gene therapy to treat Hemophilia A, the most common type of Hemophilia, showed that all 9 patients stopped using clotting factors; bleeding events also fell dramatically. “[Patients’] bleeding rates collapsed to zero or nearly zero and we’ve improved their quality of life beyond recognition.”

Research Updates

1) FDA Approves Spark Therapeutics’ Blindness Treatment

The FDA approved the third ever gene therapy, Luxturna (voretigene neparvovec-rzyl), to treat children and adults with hereditary retinal dystrophy.  The disease causes vision loss and may lead to blindness.

2) Genetic Differences Could Impact Efficacy and Safety of CRISPR

Gene editing technology may need to be tailored to each patient’s specific genome sequence to maximize treatment effectiveness and prevent side effects.

3) CRISPR may Treat Hearing Loss

Scientists successfully restored hearing in animals by injecting CRISPR-Cas9 into mice cochlear hairs.

4) Gene Therapy Restores Functional Hemoglobin for Sufferers of Sickle Cell Disease

LentiGlobin gene therapy may enable those with sickle cell disease to forego transfusion, potentially outperforming the yet-to-be-approved drug therapies crizanlizumab (Novartis) and voxelotor (Global Blood).

5) From Hospice to Hope: Encouraging Results for Myeloma Gene Therapy Treatment

Bluebird Bio announced encouraging Phase 1 dose-escalation study results for patients suffering from advanced multiple myeloma.  After receiving bb2121, 94% responded to the treatment and 56% remained in remission. Some patients were headed to hospice before receiving treatment.  "This is unheard of, something that we haven't seen with any drugs approved for myeloma in this type of population. The excitement among all the myeloma providers is crazy."

6) Bypassing the Blood-Brain Barrier for Neurological Diseases

Genetically engineered microglia, brain immune cells, inserted into brain ventricles may regenerate brain tissue and treat brain diseases, say researchers.  Injecting cells directly into the brain allows them to more quickly multiply and begin repairing damaged tissue.

7) Clinical Trials in Sight for Duchenne Muscular Dystrophy Gene Therapy

By replacing a faulty gene with an engineered one, a researcher believes he can treat Duchenne muscular dystrophy.  Solid Biosciences licensed SGT-001 and has begun clinical trials for the treatment.

8) CAR-T Therapy Updates

9) New Viral Vectors May Prevent Immune Response to Gene Therapy

Recent research has shown promise in using new viral vectors to prevent gene therapy immune responses, which may neutralize vectors and pose other hazards to patients.

Other News

1) Gilead Buys Cell Design

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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.