Additional resources for patients and families

Gene therapy is the use of genetic material (DNA or RNA) designed to treat or prevent illness. It is a way to treat inherited conditions that are caused by changes in a person’s genes. Genes are like the blueprints for our body, and gene therapy aims to help fill in missing parts or correct errors in the plans.

Genes provide instructions on how the body makes proteins that are needed for proper function. A change (mutation) in a gene is a small difference in DNA that can change the instructions and change how proteins are made and how they work. This can affect things such as how well a person is able to walk, breathe, and digest food.

Gene therapy is designed to treat the root causes of rare conditions, such as changes in certain genes. The goal is to deliver genetic material (DNA or RNA) to correct the way that cells produce proteins. If gene therapy is received early, it may be able to stop serious damage before it happens. However, this is still being researched. More information needs to be gathered in order to learn about the long-term safety and efficacy of gene therapies.

There are 3 main approaches to the use of genetic material to treat rare conditions.

• Gene addition, also known as gene replacement, is a one-time procedure that adds a new gene that contains the instructions for a cell to make the kind of protein that is needed
• Gene silencing tells cells to decrease the amount of a protein that is being made
• Gene editing uses very precise technology to change or remove information within a particular gene

Exons are segments of genes that are linked together in a string to provide the instructions for making proteins. If a mutation occurs, such as when one or more exons in the string are missing, the body can’t read the genetic instructions correctly. By “skipping” over certain exons, new connections can be made that enable the body to make a shortened version of the needed protein.

Clinical studies measure the way an investigational product will act within the human body, and will evaluate if it is safe and effective. Clinical studies are performed in several phases, each of which gathers additional information.

There are several different stages an investigational product goes through along its path of development to treat rare conditions.

• RESEARCH 
  Scientists in the laboratory discover a new compound.
• PRE-CLINICAL 
  Researchers test the investigational product’s safety and the effect it has in animals.
• EARLY-STAGE CLINICAL 
  Investigators study the dosage and effect of the investigational product in small groups of people. Safety and side effects are also recorded.
• LATE-STAGE CLINICAL 
  Larger groups of people who have the condition being studied receive the investigational product. These studies help to confirm whether the product is effective and establish its safety profile (including side effects). These studies may also compare the product with a placebo or with current or similar treatments.
• APPROVAL 
  After FDA review, the new product may receive approval for doctors to prescribe it.
• REAL WORLD EVIDENCE (RWE) STUDIES 
  After approval, studies continue to follow participants over time, gathering real-world, evidence-based information.

Each study has specific rules for who is eligible to take part. Your doctor can help you identify a study that may be a good fit for you or your child. If you think you may be eligible, contact the study organizers to learn more. You may also contact us at advocacy@sarepta.com for information about how to find and join a study.

If you and your doctor find a study that you might qualify for, the organizers will help determine if you or your child meets the requirements for joining (this is called the screening process). They will also take you through the informed consent process to make sure you have the information you need before you participate.

When you enroll in a study, you’ll receive information about costs, reimbursement, and if compensation is available. In general, clinical studies use unpaid volunteers, but you would receive the investigational product(s) at no cost. Some studies may also help with out-of-pocket expenses like travel, and some are able to provide stipends. Every study is different, and it is best to discuss this with the investigators before you make any decisions.

Many clinical studies have sites in different locations and countries, to ensure that the largest number of people can participate. Most studies require regular medical procedures, tests, examinations, and sometimes a stay in a hospital. It may be hard for you to keep up with the trial requirements if you live far away from a study site. Your doctor and the study organizers can help you decide if the trial location and travel needs would be a hardship for you or your loved one.

No. The efficacy and/or safety of a new product is not really known until after clinical studies have been performed. Not all investigational medicines are found to be effective or safe, so your decision to participate is a personal one you should make with advice from your doctor and the study organizers.

Yes. The study organizers always strive to ensure that no one is at high risk for harm. While clinical studies offer you a chance to try an investigational product, you should be aware that:

• the product may cause side effects, including serious ones
• the product may not work for everyone
• you may not receive the product being studied but may be given an inactive treatment such as a sugar pill, or another type of treatment that is already approved; there will be no way for you to know which treatment you are receiving
• the time and effort that are needed may become a hardship for you if you have to visit the study site often, stay in a hospital, have regular tests, or follow very strict directions

The U.S. FDA and the regulatory agencies in other countries are responsible for safeguarding public health by ensuring that current and new medical products are safe and effective. These agencies define the standards and structures for the clinical trial process, especially around informing and protecting participants.

Researchers need to provide information about the clinical trial so that potential study participants understand the risks, potential benefits, and alternatives to the study.

Before a clinical trial is started, its design must be reviewed and approved by an Institutional Review Board (IRB) made up of doctors, researchers, and members of the community. At all stages of the trial, the IRB helps ensure that the research is ethical and the rights and welfare of participants are protected.

During a trial, results may also be reviewed by an independent team of experts called a Data Monitoring Committee (DMC) or Data Safety and Monitoring Board (DSMB), who check for any concerns related to drug safety. The DMC or DSMB can recommend to regulatory authorities or the researchers that the trial be stopped at any time if the study is not effective, is harming participants, or is unlikely to serve its scientific purpose.

Clinical trials are designed to measure specific goals called endpoints. These endpoints help the investigators understand how the investigational product performs, and its potential benefits and risks to participants. There are 2 types of endpoints:

• Clinical endpoints directly measure whether you feel better, function better, or live longer with the treatment.
• Surrogate endpoints may be used instead of clinical endpoints in some studies, as they are a measure that is reasonably likely to predict clinical benefit. They use biomarkers—a physical, biochemical, or genetic characteristic that can be objectively measured.