monthly gene therapy business review

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. 

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. 

Landmark Month Sees Second Gene Therapy Approved and Other Wins

RxC International Gene Therapy Newsletter

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

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

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


Pricing Debate Intensifies with Approval of First Gene Therapies

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

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


Gene Therapy Pricing and Target Patient Population


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

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


Harvard Scientists Reveal New Gene Editor

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

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


Research Updates

Second Gene Therapy Treatment Approved

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


Fitusiran's Recent Failure Opens Door for Additional Therapies

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


Gene Therapy Receives Unanimous Recommendation for Approval

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


Encouraging Results for Gene Therapy Treatment of Fatal Neurodegenerative Disease

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

About RxC International

Understanding the subtleties of the gene therapies is critical for bringing these treatments to market. RxC International has extensive experience successfully commercializing and launching new drug products, developing innovative solutions, realizing a product’s best potential, and working across organizations to achieve common goals.

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

About the Author

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