Gene Therapy

Part
01
of four
Part
01

RDEB Caregiver Journey

The RDEB caregiver journey starts with the proper diagnosis of RDEB disorder. Once a child is confirmed to suffer from RDEB, then the parent needs to adjust appropriately and develop an effective schedule to take care of the child. Below is a summary of the caregiver journey:

Diagnosis

  • The RDEB caregiver journey starts when a child is diagnosed with the disease. The first step is to perform an RDEB laboratory diagnosis.
  • Laboratory diagnosis is very important for RDEB patients because it identifies the correct strain of ED the child is suffering from. This also allows for the genetic profiling of the parents, personalized medication, and effective participation in trial therapy programs.
  • Genetic testing and sampling of skin samples are the main processes used for RDEB diagnosis. When diagnosing infants, sample skin sampling is recommended.
  • To rule out or confirm EB disorder, the parent and the child will undergo a series of tests for some time. Only qualified professionals working in recognized institutions with DREB specialization are recommended to carry out EB diagnosis.

Establishing a New Schedule for EB Care and Management

  • Once a child is confirmed to have RDEB, the parents embark on a difficult journey of caring for the patient and managing the disease. This is because while research on various treatment options is ongoing, there is no confirmed cure for the diseases. RDEB care and management involve:

Podiatry (Foot Care)

  • According to the EB registry, 33% of all EB patients suffered from dystrophic nails. The most prevalent foot toe disorders are EB simplex (90%), dominant dystrophic EB (83.25%), and recessive dystrophic EB (94.8%).
  • Deformed nails often get caught on things giving the patients painful experiences. Since they get abnormally hard, they are difficult to trim.
  • For proper management of dystrophic EB varieties, the parent is expected to come up with a schedule of grooming their child.
  • The recommended procedure for foot care involves making a 2-liter salt (45g) solution of lukewarm water, soaking the feet to soften the nails, and then filing them with an emery board. Nails should be trimmed straight across. This process should be done once per week for children.

Wound Care and Pain Management

  • Wounds caused by RDEM start by forming blisters. These blisters can metastasize and cause bigger wounds. This can lead to the damage of nerve endings on the skin causing a 'burning pain' to the patient.
  • When caring for these wounds, the caregiver should start the process by preparing the dressing materials, drain the blister by making entry and exit holes on it, placing a protective soft cloth on the wound, and leaving the blister roof intact. Remove any dead skin that forms around the would. Parents should consult with specialists for any topical pain relievers.
  • This is a daily routine as it is hard to predict when and where wounds will appear. Parents are encouraged to develop regular exercising schedules with their children. This helps in preventing deformity of their limbs and an altered gait among others.

Psychological Counseling

  • Both caregivers and juvenile patients of RDEB need strong psychological support. This can be given free of charge in EB centers or closed groups.
  • Usually, both the parents and children (when they get to a school-going age), need advise on a wide range of things such as financial help, education, and even bereavement support.

Joining an RDEB Support Community

  • Due to the traumatizing nature of RDEB on patients and caregivers, it is advisable for parents to join support groups in their locality on the internet.
  • Joining these groups is free as long as one is an EB caregiver, patient or supporter. The journey for joining an EB group starts by signing up on the group's website.
  • Once one becomes a member, they get infallible information on how to care for patients, details on ongoing treatment trials, counseling, and the opportunity to attend EB meetings in the area.
  • Support groups also fundraise to offer financial support to group events and trial treatment programs. For instance, the total funds used to support the direct-to-client program by DEBRA International in 2018 was $3 million. It also supports a total of 25 research programs related to EB.
  • The groups also offer special support to patients and families living with EB. For example, the U.K. based RDEB support group is offering up to 2 weeks of subsidized holidays for its members. These facilities are specially designed to give memorable holidays for patients and their families.
Part
02
of four
Part
02

Gene Therapy Solutions: RDEB Companies

Companies working on gene therapies for RDEB are communicating the value of gene therapy as a solution to potential patients by emphasizing that it is a treatment that goes beyond palliative care and that it could make a difference in the patients' lives by treating the underlying cause of RDEB.

Communicating the Problems Gene Therapy Can Solve

  • Companies working on RDEB gene therapies bring the incurable, painful, and fatal nature of this disease to the fore when presenting the problems gene therapy can solve for RDEB patients.
  • The website of Fibrocell describes RDEB as a devastating and painful disease that causes severe blistering on a patient's skin due to a mutation in a collagen-producing gene. The company states that its gene therapy could help a patient's cells produce enough collagen for the layers of their skin to hold together.
  • Krystal Biotech's website explains that RDEB is an incurable and often fatal skin disease. The company also states that current treatment for this disease is limited to palliative care. Krystal Biotech notes that it is developing KB103 gene therapy for the treatment of RDEB.
  • Krystal Biotech presents gene therapy as a technology that can make a difference in the lives of underserved patient populations with debilitating skin diseases.
  • Abeona Therapeutics's website describes gene therapy as potentially offering a cure for serious illnesses. The company's patient and family web page notes that it is developing gene therapy for RDEB after describing the difficulties of this disease such as blistering, wounds, and cancer.

Communicating Gene Therapy as a Solution

  • Fibrocell, Krystal Biotech, and Abeona Therapeutics all used web pages specifically designed for patients and their families to communicate gene therapy as a solution for RDEB. These companies also emphasized that gene therapy is an alternative to palliative care.
  • The Fibrocell website has a web page designed for RDEB patients and their families. On the right side of this page, there is a prominent link that encourages patients to learn more about the use of FCX-007 gene therapy as a treatment for RDEB. Following this link leads to a clinical trials page that uses text, patient photos, and diagrams to communicate gene therapy as a solution.
  • The Fibrocell website notes that current treatments for RDEB, such as bandaging, antibiotics, feeding tubes, and surgeries, only address the disease's symptoms rather than its underlying cause. Fibrocell asserts that its therapy can treat the underlying cause of RDEB by providing high levels of a collagen gene to the patient's fibroblast cells, which are then injected into the affected areas of the patient's skin. It also notes that its gene therapy process avoids systemic treatment.
  • Krystal Biotech lists its gene therapy as an alternative to the current standard of care for RDEB, which is palliative treatment. Krystal Biotech also notes the value of its gene therapy over other viral gene therapy systems because it is topical, can accommodate large genes, may transfer genes more efficiently, is non-replicating, can be re-administered, and does not disrupt a patient's genome.
  • Abeona Therapeutics has a patient and family section on its website. The company emphasizes the value of gene therapy as a solution by noting that the only treatment currently available for RDEB is bandaging the patient's wounds and that the average cost of bandaging is $120,000 per year. On the clinical trial page for RDEB gene therapy, Abeona Therapeutics lists endpoints such as 50% healing in treated wounds and decreased pain for patients with the disease.

Communicating the Promises, Capabilities, and Science of Gene Therapy

  • Companies working on RDEB gene therapies describe the promise of gene therapy as offering hope and relief to patients who are suffering from rare skin conditions. These organizations claim that their therapies can heal patients' wounded skin. The science of gene therapy is generally explained to potential patients using diagrams and text which describe the process of reprogramming cells with a vector so the cells can produce normal collagen proteins.
  • Fibrocell's website describes the science of gene therapy to potential patients through text and diagrams showing how a patient's fibroblast cells will be collected, altered with a virus to express a new collagen gene, and then delivered topically back onto the patient's skin. The company also includes a brief video explaining how its process was optimized to reduce the chances of rejection.
  • Fibrocell describes its gene therapy as having the capability to be a localized therapy for RDEB that is uniquely compatible with each patient's biology. The company's website states that the promise of gene therapy offers hope and relief to patients suffering from rare skin and connective tissue diseases. Fibrocell also believes gene therapies have the potential to transform patients' lives and the future of medicine.
  • The Krystal Biotech website explains the general science of gene therapy to patients in short articles about its viral vector system that include text and simple diagrams. The company notes that gene therapy has the promise to introduce therapeutic genes into patients' cells and can be used to develop topical treatments for rare dermatological conditions.
  • Krystal Biotech describes the science of RDEB gene therapy to potential patients in the patients and families section of its website. The company uses paragraphs of text and detailed diagrams to explain how its therapy inserts collagen genes directly into a patient's cells by topical application onto wounds. Krystal Biotech notes that this process has the capability to stabilize a patient's otherwise fragile skin.
  • Abeona Therapeutics explains on its website that gene therapy is the use of DNA to potentially treat a disease, usually by delivering a correct copy of a gene into a patient's cells. The company describes the promise of gene therapy as transformative for patient care and potentially offering a cure for serious illnesses.
  • Abeona Therapeutics communicates the science of gene therapy to potential patients who may enroll in the company's RDEB clinical trials via a paragraph explaining how a new collagen gene will be inserted into the patient's cells and the patient will receive transplants of new patches of skin cells. This web page also describes the potential capabilities of this treatment to heal wounds.

Research Strategy

Information concerning Abeona Therapeutics's RDEB gene therapy was sourced from the Abeona Therapeutics website. Information about Krystal Biotech's RDEB gene therapy system was gathered from the company's website. Notes about Fibrocell's RDEB gene therapy program were collected from Fibrocell's website. Fibrocell, Abeona Therapeutics, and Krystal Biotech were selected as examples for analysis because of their location within the United States and because of the companies' ongoing clinical trials for RDEB gene therapy.



Part
03
of four
Part
03

Gene Therapy Solutions: Gene Therapy Companies

Companies working on gene therapies are communicating the value of gene therapy as a solution to potential patients by emphasizing it as a novel, personalized treatment and explaining its potential to treat patients who have few other options.

Communicating Problems Gene Therapy Can Solve

  • Companies are communicating with potential patients about which problems gene therapy can solve through specially designed patient websites, brochures, and discussion guides.

Communicating Gene Therapy as a Solution

  • Communicating gene therapy as a solution to potential patients' diseases may take the form of simplified written explanations, patient stories, or patient discussion guides. These materials note the benefits of specific gene therapy treatments and tout their potential to provide health improvements for patients who have few other options.
  • Patient communications on the Kymriah patient website note that this treatment is individualized, uses the patient's own immune cells, and may put the patient's cancer into lasting remission. On the page about pediatric leukemia treatment, there are also some simplified versions of these statements for children which explain that Kymriah has helped treat other children with cancer. The patient websites also feature the stories of patients who used this gene therapy for treatment.
  • On the Kymriah patient website, stem cell therapy and chemotherapy are listed as other potential treatment options. Kymriah is presented as an alternative to these without making specific statements as to how it is more effective or beneficial than other treatment options. Since the therapy is marketed those with relapsing or refractory cancers, having another chance for treatment is an important selling point.
  • The patient website for Luxturna emphasizes that treatment can restore normal RPE65 protein production in the patient's retinal cells and that this will improve vision. The website also notes that improvements in functional vision increased patients' abilities to do their daily tasks and to navigate in low light settings.
  • Luxturna's patient website does not indicate how Luxturna compares to other treatment options for inherited retinal disease because it is currently the only treatment available.
  • Novartis's Yescarta patient website notes that gene therapy is different from other treatments because it uses a patient's own reprogrammed white blood cells to destroy cancer. The therapy offers cancer patients a chance for complete remission.
  • The Yescarta patient website features stories of patients who turned to Yescarta after other treatments failed. A discussion guide about Yescarta shows alternative treatment options such as participating in a clinical trial, pursuing other second line therapies like chemotherapy and radiation, and supportive care. The guide notes that different choices may be made based on the patient's cancer type, preferences, and overall health.

Communicating the Promises, Capabilities, and Science of Gene Therapy

  • Scientific explanations about gene therapy which are targeted to potential patients are usually very simple and focus on the involvement of the patient's own cells. Patient websites focus on the capabilities of a specific therapy without making statements on gene therapy in general.
  • The Kymriah patient website explains the science of gene therapy with simplified pictures of reprogrammed immune cells and a 12-minute video. The capabilities of the treatment are also described on the Kymriah website. This website does not make any statements about the promise of gene therapy in general but does tout Kymriah specifically as a treatment with the potential to treat relapsing and refractory cancers.
  • The Luxturna website explains the science of gene therapy via a simple digital flowchart describing how the therapy will deliver a functional gene into the patient's retinal cells. The website notes Luxturna's capability to treat specific inherited retinal diseases. This website does not make any statements about the promise of gene therapy in general but does advertise Luxturna specifically as a treatment with the potential to improve vision in those with retinal diseases caused RPE65 mutations.
  • A brochure for potential Yescarta patients explains the science of gene therapy using simple drawings of immune cells and a description about how T-cells are reprogrammed to better recognize cancer cells. A discussion guide also explains the process of Yescarta gene therapy to potential patients.
  • While the Yescarta website does not comment on the promise of gene therapy as a whole, it describes Yescarta as a treatment with the capability to offer complete cancer remission to patients for whom other therapies have failed.

Research Strategy

Information about Kymriah was sourced from Novartis's Kymriah patient website. Information about Luxturna was sourced from Spark Therapeutic's Luxturna patient website. Information about Yescarta was gathered from Novartis's Yescarta patient website. The current treatment landscape for patients with inherited retinal diseases was gleaned from a scholarly review article. This brief focused on Kymriah, Luxturna, and Yescarta because these treatments were among the first FDA-approved gene therapies on the US market.
Part
04
of four
Part
04

Gene Therapy Solutions: Insurance Companies / Advocacy Groups

Insurance providers such as CVS Health and Cigna, along with advocacy groups such as The National Organization for Rare Disorders (NORD), Alliance for Cancer Gene Therapy (ACGT) Foundation, and the EB Research Partnership, all communicate the value of gene therapy to their patients and customers in a variety of ways. From touting the potential from initial clinical trials and drug approvals, reiterating the promise of gene therapy and research into the genome, and talking about the promises ahead, based on a general description and break down of the scientific principles that make these therapies so effective for a vast array of illnesses.

CVS Health Insurance

  • CVS Health states that gene therapy will provide novel therapies for aggressive cancers, as well as hereditary conditions like ocular disorders, hemophilia, and cystic fibrosis. Gene therapies will provide new hope to patients with a vast array of conditions that once had few or no treatment options, and required a lifetime of management.
  • These treatments utilize genetic engineering to replace or repair mutated and damaged genes, effectively treating the patient’s medical condition from a genetic level. Using viruses to deliver new genetic material, CVS Health states that these vector-based gene therapies are also in development for the treatment of immune disorders, certain forms of brain cancer, and sickle cell disease, among others.
  • Gene therapies work by utilizing different means and mechanisms to alter and change an individual’s genes or to modify the expression of a gene product, in order to prevent, treat, or cure disease. Gene therapies are highly personalized, and there are several other therapies in the pipeline that could be approved and launched in the near future, with even more treatments are in earlier stages of development which could be launched in later years. The pipeline for gene therapies and their potential is robust and set to grow and flourish.
  • Gene therapies insert DNA containing a functioning gene into a cell, to replace a faulty or missing one, thereby correcting the effects of a disease-causing mutation in the genome. In order for the therapy to work, the new DNA must reach the damaged cell and enter it, and either express or disrupt a particular protein. This same genetic disease process applies to thousands of diseases, and so there is great potential for gene therapy to help many people and relieve tremendous suffering for countless patients with varying genetic disorders, providing the promise of a potential cure.
  • CVS Health states that in ex vivo gene therapy, the target cells containing the faulty or missing genes are extracted from the patient and re-engineered in a lab to integrate a new and functioning gene into the chromosome. The newly reprogrammed cells are then put back into the patient, with the new gene being distributed through the patient’s system as these cells multiply.
  • In addition to those already approved by the FDA, many other gene therapies are in currently in development, which could help and even cure other previously untreatable life-threatening conditions. Some gene therapies target relatively rare illnesses, such as Sanfilippo syndrome, cerebral adrenoleukodystrophy, and adenosine deaminase deficiency, while other treatments with potential approval by 2021 include more common genetic disorders, such as hemophilia A and B. Both sickle cell disease and muscular dystrophy could also have gene therapies available by 2023.
  • CVS Health states, "The age of the genome, and gene therapies, is upon us and we should all applaud and support the promise it brings to alleviate a tremendous amount of human suffering."

Cigna Insurance

  • Cigna Insurance believes and communicates to customers the promise of gene therapy of curing deadly diseases by administering a one-time therapy that rewrites a patient’s genetic code. They believe in the therapy's potentially curative medicines and life-altering cures, offering great promise for patients and families.
  • Cigna allows two gene therapy treatments as of now in their insurance coverage, Luxturna, the first FDA-approved gene therapy for inherited retinal disease, and Zolgensma®, a gene therapy for children under 2 years old with spinal muscular atrophy. They state that additional therapies will most likely be added in the future as they are developed, as they recognize that these are the first two in a long lineup of gene therapy drugs being developed in the future with the potential to treat a vast variety of illnesses.
  • Steve Miller, M.D., Cigna's Executive Vice President and Chief Clinical Officer said, “We are leveraging our collective capabilities to deliver on the true promise of modern medicine. No cure should be out of reach of any patient, and they should receive the best quality care.”
  • Cigna states that gene therapy offers innovative treatments for devastating conditions, along with long term health and positive life changing results, "allowing families to hope for a cure and a brighter future.

The National Organization for Rare Disorders (NORD)

  • NORD states that gene therapy offers great promise for those with genetic diseases that once had no cure or effective ways to relieve suffering.
  • Gene therapy can be given systemically (to the whole bodily system) or applied locally to the affected area. Systemic treatment has the potential to reach all somatic cells in the human body, though gene therapy is more often targeted toward only the diseased cells.
  • Although having great promise, NORD says that every person has different DNA so that some gene therapy may work better with some patients over others, with variability in the success of the drug, especially in these early trial stages.
  • NORD states that the effectiveness of gene therapy may reduce other medical symptoms besides those targeted, thus reducing medical costs.

Alliance for Cancer Gene Therapy (ACGT) Foundation

  • The ACGT Foundation helps research and develop innovative and groundbreaking gene therapies for patients with rare diseases, especially cancer.
  • ACGT's genetic therapy for solid state tumors "represents the next generation of gene therapies," says the executive director of the advocacy group. They are using gene therapy for the development of cancer vaccines, one of the most promising forms of gene therapy.
  • ACGT states that "cancer gene therapy science is proving to be life-changing for patients and we are proud to be a part of it."
  • With gene therapy, they have created tumor-targeted, active herpes viruses to infiltrate cancers and thus stimulate an immune system attack on those cancer cells. Dr. Joseph Glorioso says that compared to other conventional treatments that kill everything this gene therapy is like a "heat-seeking missile that targets metastatic cancer for destruction." Even when the cancer is eliminated, the vaccine creates an immunity in the body to protect against disease recurrence. Melanoma is among the most deadly cancers and this treatment offers patients new hope for the future.

EB Research Partnership

  • Patient advocacy group EB Research Partnership says that perhaps the greatest promise for treatment of RDEB or recessive dystrophic epidermolysis bullosa, is gene therapy. Scientists have successfully been able to correct a patient's cells on a genetic level and then graft those cells back on to the patient.
  • EB Research believes that for RDEB we are on the precipice of a cure. By fixing a single mutation, we can change the lives of many. They state that the methodology that they pioneered to develop a cure holds the key to helping millions suffering from other rare diseases as well.
  • They state that of the 7,000 known orphan diseases, 5,400 of them are genetic in origin like RDEB, and so breakthrough gene therapy for RDEB alone could potentially affect 10% of the population, or 30 million people.
Sources
Sources