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

Sign Up for More

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

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. 

Sign up for our monthly gene therapy newsletter.

Name *

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.

Click Here to Subscribe to Our Monthly Gene Therapy Business Review

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.


  • 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.


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

Sign up for our monthly gene therapy newsletter.

Name *

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

Sign Up for More

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

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. 

Monthly Gene Therapy Business Review - November, 2017

RxC International Gene Therapy Business Review November Newsletter

November saw some important moments in gene therapy.  We have summarized the most noteworthy and included the remaining in our news and updates sections.

RxC International reviews gene therapy developments and commercialization efforts on a monthly basis.  Sign up here to have our newsletter delivered to your inbox.

1) FDA Accelerates Gene Therapy Process but Warns of Unregulated Risks

Regulators and legislators are balancing speed of approval with warnings about administering unapproved therapies that have not had testing in a regulated environment.  This shows an understanding by government entities of the potential benefit from new therapies and the harm from unregulated treatments.

This month, the FDA issued new guidelines to accelerate the approval of gene therapies.  The FDA’s announcement came less than a week before Tristan Roberts became the first person to self-inject an untested gene therapy, demonstrating the rise of unregulated gene therapy use among “biohackers” and regenerative medicine clinics. The FDA issued another statement warning against self-administering gene therapies and cautioning against unregulated treatments.  

A week prior to Roberts’ action, the Senate Health, Education, Labor and Pensions Committee convened a hearing to learn more about gene therapy and its implications.  “While CRISPR and other gene editing technologies could transform human health, it’s not hard to see how we can quickly get into societal and ethical issues,’” said Senator Lamar Alexander. Added Senator Susan Collins, “We live in a global world and it seems like the scientific advancements have outpaced policy in this area. So how do we ensure this exciting breakthrough in gene editing is to be used for good in China, Russia and the U.S.?"

2) Will Gene Therapy Replace the World’s Most Expensive Drug?

Pricing has always been one of the biggest questions in gene therapy’s broad success in the market and will certainly continue to play a significant role in the ability of patients to access treatments.  The case of AVXS-101 will test pricing models and the willingness of payers and other entities to pay for combination therapies.

While the gene therapy may carry a hefty price tag, it is a one-time treatment; Spinraza, on the other hand, costs $750,000 for the first year of treatment and hundreds of thousands of dollars for each subsequent year.  The biggest question is what an acceptable price?

Spinraza, approved last December as the first treatment for spinal muscular atrophy (SMA), may soon have competition from a gene therapy.  This month the New England Journal of Medicine published an article detailing success in early clinical trials for AVXS-101, a gene therapy that also treats SMA.  Whereas Spinraza forces a gene within the body to produce short motor neurons (SMN), a protein SMA sufferers lack enough of, the new gene therapy replaces the defective gene.  

This chart illustrates the Children’s Hospital of Philadelphia (CHOP) Infant Test of Neuromuscular Disorders (INTEND) score for patients in Cohort 1 who did not receive the gene therapy and patients in Cohort 2 who did receive the gene therapy. Source:  NEJM

This chart illustrates the Children’s Hospital of Philadelphia (CHOP) Infant Test of Neuromuscular Disorders (INTEND) score for patients in Cohort 1 who did not receive the gene therapy and patients in Cohort 2 who did receive the gene therapy. Source: NEJM


Results from the 15 patients who received the gene therapy were impressive; all were alive at 20 months without needing permanent ventilation, a milestone only 8% of untreated patients reach. Even with these promising results, researchers don’t know whether the positive effects will last and whether a second administration of the gene therapy is even possible.  

3) Global Treatment Model May Be Necessary for Commercializing Gene Therapies

Rare diseases and specialized skills will require international collaboration for gene therapy success.  As this example illustrates, commercializing gene therapies poses challenges that traditional drugs have not faced, including small disease populations, the level of physician expertise required, and special treatment facilities. Questions about where patients receive treatment, who should administer treatment, and, of course, how to pay for these treatments will continue to challenge the development of gene therapies.

Despite uncertainty surrounding internationality and commercialization, this case may be particularly valuable as a blueprint for future gene therapies.  

Two years after receiving a life-saving skin grafting procedure, a boy suffering from junctional epidermolysis bullosa (JEB) remains healthy.  To treat him, doctors grew nine square feet of new skin, enough to cover over 80% of his body.

Of particular interest is the internationality involved in this case.  The child is from Syria but was hospitalized in Germany and treated by Italian doctors granted a compassionate use exception for unapproved treatments.  The boy’s new skin was grown in Italy and transported back to Germany where it was grafted onto his body.

4) Gene Editing within the Body: A New Frontier

A breakthrough this month illustrates the potential of non-CRISPR therapies as well as the need for continuing research and development of wide-ranging gene therapy applications and capabilities.

Brian Madeux made history by being the first person to have his genes edited within his body.  Madeux, suffering from a genetic disorder called Hunter syndrome, received an injection of zinc-finger nucleases to cut and paste a missing gene into his DNA.  If successful, the treatment will enable Madeux’s liver to break down certain molecules and halt the progression of his disease.

While animal testing of this gene therapy were encouraging, the results of Madeux’s treatment will not be known for several months.

5) Gene Therapy May Treat Meth Addiction

Unlike cancer gene therapies that turn off defective genes or other therapies that replace faulty genes, the anti-meth therapy introduces a new gene in the body that produces antibodies to assist with warding off chemical addiction. This application of gene therapy technology demonstrates that these therapies are not a uniform group of CRISPR opportunities but are varied and capable of broad application.

A team at the University of Arkansas for Medical Sciences has created a gene that codes an anti-methamphetamine antibody to prevent meth particles from traveling to the brain and creating euphoria.  Researchers hope that this breakthrough, combined with behavior therapies, will help meth addicts to overcome the addiction.

6) Virus Shortage Threatens Gene Therapy Success

A virus shortage highlights the need for companies to have a comprehensive commercial roadmap very early in a new gene therapy’s development or risk being shut out of the industry entirely.  With so many companies focused on clinical trials and approval pathways, commercialization issues may fall by the wayside to the detriment of efforts to get much-needed treatments into the hands (or genes) of patients.  

The biggest roadblock to successfully developing a gene therapy may not be regulatory or fiscal.  The New York Times reports that few companies have the production capability to create viruses necessary for gene therapy delivery and even fewer drug companies have these capabilities in-house.  “The result is a logjam. Firms exploring new gene therapies may wait for years in line for bespoke viruses.”

To avoid development delays, forward-thinking gene therapy companies are buying one or more virus production slots years in advance. One biotech company has gone so far as to invest hundreds of millions of dollars to make its own plant for manufacturing viruses. “‘We don’t want to be in a queue, that’s for sure,” said Robert Baffi, head of technical operations at BioMarin.

Research Updates

1) Encouraging Results for Gene Therapy Treating Heart Failure

A recent study of 13 pigs showed the potential of gene therapy to treat heart failure.  Of the 6 pigs who received the gene therapy, heart failure in the left ventricle was reduced by 25% and heart failure in the right ventricle was reduced by 20%; the pigs’ heart sizes were reduced by 10%.

2) Gene Therapy May Treat Rett Syndrome

Researchers have come closer to treating Rett Syndrome, a disease that causes acute impairments affecting speech, mobility, and breathing.  

3) Novartis partners with Homology Medicines to Evolve Genome Editing Technology

Novartis and Homology Medicines have teamed up to explore the therapeutic potential of adeno-associated viruses (AAVs) as an alternative to CRISPR for some diseases.

4) Canavan Disease Breakthrough Illustrates Complexity of Bringing Gene Therapies to Market

While gene therapy may offer hope for sufferers of Canavan disease, a disorder that damages nerve cells in the brain, the development of a treatment remains a lengthy and complex process.

5) Gene Therapy for Young-Onset Parkinson’s in Development

Synpromics and UCL are partnering to develop a gene therapy for young-onset Parkinson’s that focuses on higher-level gene expression using “novel, purpose-designed sequences tailored to different gene expression profiles.”

6) Researchers Discover Key to Regenerating Blood Vessels

Researchers have identified a signal pathway critical to growing new blood vessels from existing ones (angiogenesis).  

7) Phase 1 Parkinson’s Trial Announced

Voyager Therapeutics announced that it is recruiting for Phase 1 trials for VY-AADC01, a gene therapy that codes for the enzyme l-amino acid decarboxylase.

8) Gene Therapy Shows Promise for Treating Cystic Fibrosis Bacterial Lung Infections

Gene therapy delivery to airways may greatly enhance the treatment success of bacterial lung infections due to cystic fibrosis.

9) Nanoparticles for Death-Induced Gene Therapy to Treat Cancer

A new study indicates tolymeric or inorganic nanoparticles may be the key to gene therapies that kill tumor cells.

10) Study Offers Hope for Relapsed Leukemia Patients

According to trial results published by Stanford, 73% of patients who received a new gene therapy for treatment-resistant B-cell leukemia entered remission.  

Other Gene Therapy News

1) Farming Industry Embraces Gene Therapy to Speed Breeding

Gene therapy is extending beyond the pharma industry as a tool used in agriculture to breed for certain traits. Using CRISPR will allow the breeding process to be expedited. “We can do in six months now what used to take us six or seven years,” says James C. Collins Jr., chief operating officer of the agriculture division at DowDuPont.

2) World’s Smallest Tape Recorder

Scientists have modified the bacterium Escherichia coli into a micro tape recorder. “By responding to chemical changes in the surroundings and then 'time-stamping' them in DNA, the technology paves the way for living monitoring devices that could be used in health screens or to analyse pollutants in ecosystems.”

To receive RxC International’s monthly newsletter on gene therapy advancements and commercialization efforts, sign up here.

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.