“5 Things to Know” is a new, quick digest from Cure Sanfilippo Foundation of five things especially relevant to the Sanfilippo Syndrome community. We are going to send these regularly to keep you updated and put information and resources at your fingertips.
1. Your life with Sanfilippo is a goldmine of insights that can change the future
Each experience, milestone, and challenge within a life affected by Sanfilippo Syndrome holds important insight. Your journey matters, and joining SanfilippoLINK, the secure, global clinical research and patient-voice registry platform for Sanfilippo syndrome, enables you and your child’s life to play a direct role in informing researchers and clinicians working to advance meaningful treatments and improve healthcare for everyone with Sanfilippo Syndrome.
SanfilippoLINK has been designed by Cure Sanfilippo Foundation to fill the critical gaps in knowledge needed for the successful development of future treatments for all forms of Sanfilippo – and to collect data that could help support long-term access for everyone. It’s a way to turn your lived experience with Sanfilippo into a broader legacy, especially those of angel families, that directly impacts future generations of children.
We invite you to learn more about SanfilippoLINK and the easy steps to begin participating at SanfilippoLINK.org. You can also reach out to us with questions or help with creating your account at Info@SanfilippoLINK.org.
2. Positive signals and actions from interim FDA leadership
The current FDA leadership team, while an interim one, has been taking actionable steps to hold true to their promises regarding concern and attention to the rare disease population. In the past weeks, FDA has opened the door for previously-denied therapies to reapply (including an MPS II gene therapy), hosted a roundtable with rare disease leaders (in which Cure Sanfilippo Foundation was invited to participate), and just recently published “Lessons Learned from our Roundtable with Rare Disease Advocates.”
FDA’s release of its “Lessons Learned” from the roundtable is heartening. The document lists four important principles regarding development of therapies for rare diseases that we are excited to see the agency publicly acknowledge:
- The vital importance of including the rare disease patient perspective in medical product decisions. Hopefully, this will lead to reinvigoration of opportunity for patient communities to engage and provide important insights to FDA.
- Traditional drug development tools and large-scale clinical trials are infeasible or even impossible for rare diseases because the number of patients is typically small and the debilitation is rapid. “This reality demands that we think differently about rare diseases.”
- “Regulatory flexibility” does not mean lower scientific standards and rigor. It means using “a tailored regulatory approach to drugs that treat rare diseases … utilizing innovative trial designs, real-world evidence, and biomarkers to support a regulatory approach that addresses the unique nature of these diseases while maintaining standards of safety and efficacy.”
- Consistency across agency divisions matters. “Rare disease patients deserve consistency [from the FDA] whether the product is a new drug, a biological product, or a gene therapy.”
Read the entire statement by FDA:
https://www.fda.gov/news-events/fda-voices/lessons-learned-our-roundtable-rare-disease-advocates
3. Understanding important considerations about clinical trial exclusion criteria
Families affected by Sanfilippo and other neurologic diseases often explore a wide range of potential treatment options in hopes of helping their loved ones. It is important to recognize and respect the difficult decisions families make when navigating these very challenging circumstances.
Over the years, there have been many potential treatments tested in trials or preclinical research for Sanfilippo. Because the goal of clinical research is to generate clear and reliable evidence that can answer questions about the treatment’s safety and efficacy, regulatory agencies like the FDA and study sponsors put eligibility criteria in place to minimize factors that could impact patient safety, the ability to measure change over time on the trial’s selected outcome measures, and/or the interpretation of study results.
Examples of such exclusion criteria that have been or are reported for various clinical trials include:
- Use of investigational therapies within a specified time frame before enrolling the study (i.e. genistein, miglustat, ambroxol, anakinra, cannabidiol/cannabis, psychotropic meds)
- Previous Stem cell therapy / Gene therapy / Enzyme replacement therapy
- Vaccination within 30 days of enrollment
- Use of medications that may interfere with metabolism of study drug or patient safety
- Scores on cognitive testing or disease severity criteria
- Uncontrolled seizure disorder
- Inability to safely undergo anesthesia, MRI, or lumbar puncture (spinal tap)
- Specific limitations on gene variants (genetic mutations) accepted into the trial
- Viral vector antibody titers and T-cell responses
- And/or other criteria depending on the specific study
In some cases, a medication listed in exclusion criteria may be stopped for a certain time period before enrolling in a study. This is called a “wash-out” period and can differ based on the medication and trial requirements. After the medication “wash-out” period, the child may then become eligible to enroll. Some exclusion criteria are based on whether the child has ever received a particular therapy in their lifetime, such as gene therapy, stem cell therapy, and/or transplant, for which there is no “wash-out” period.
The requirements of clinical trials are different from those in expanded access programs (EAP). As defined by the FDA, expanded access stipulates that “Patient enrollment in a clinical trial is not possible.” Thus, if a child meets criteria for an open clinical trial, they would not qualify for expanded access (read more at https://www.fda.gov/news-events/public-health-focus/expanded-access).
Expanded access programs are less prescriptive in terms of inclusion or exclusion criteria and mainly focus on factors that could impact patient safety, rather than on the effectiveness of an experimental treatment. For this reason, it is less likely that patients who have taken other medications or treatments (either within a prior clinical trial or otherwise) would be excluded from expanded access programs, unless there is a significant safety concern.
The clinical trial landscape is always evolving and new studies are on the horizon. Information about study inclusion/exclusion criteria are typically not made available until the trial is officially activated; therefore, it can be difficult to precisely anticipate what medications, treatments, or other factors might affect enrollment. Looking at current or past trials to see their criteria can offer some insight, though each study may have unique safety and efficacy considerations that inform their inclusion/exclusion criteria.
It is always a good idea to talk with your medical doctors about medications and treatments your child has had or you may be considering for your child if you are interested in participating in future clinical trials. You or your doctor may also reach out to the clinical trial contact person (listed on clinicaltrials.gov) to discuss trial eligibility criteria specific to your child’s individual circumstances.
4. Announcement of new, permanent FDA leadership team expected soon
Currently, FDA has several interim leaders at the helm, including FDA Acting Commissioner, Acting Director of the Center for Drug Evaluation and Research (CDER), and Acting Director of the Center for Biologics Evaluation and Research (CBER). The person filling the FDA Commissioner role may only do so in an interim capacity for 210 days, so the administration is currently shortlisting who might be nominated to fill this position on a permanent basis.
Bloomberg has reported that White House policy aide and physician Heidi Overton and New York Cancer & Blood Specialists CEO Jeff Vacirca are among the finalists for FDA Commissioner. Axios also named Vacirca, Overton, and Principal Deputy Assistant Secretary of Defense for Health Affairs Stephen Ferrara as top candidates. Norman Sharpless and Alkermes CEO Richard Pops remain reportedly under consideration, and RBC analysts have proposed BIO CEO John Crowley as top pick.
Per a newsletter last week from The FDA Group, an entity of former FDA professionals and life science experts, “Alongside commissioner candidates, the White House is reportedly vetting candidates to lead the drug and biologics centers.” Bloomberg has reported that the administration aims to announce a senior leadership team alongside the commissioner nominee, and that former Oncology Center of Excellence Director Richard Pazdur is under consideration to return as a senior agency leader.
Once a FDA Commissioner candidate is named, the 210 day-clock for the interim/acting placeholder pauses while the nominated candidate proceeds through the confirmation process. Since the FDA Commissioner is a presidential appointment, the person must appear before the U.S. Senate Committee on Health, Education, Labor and Pensions (HELP) for a public hearing, and then receive a simple majority vote of the entire Senate to confirm them to the position. Directors for CDER and CBER are not presidential appointments and do not have to be confirmed.
5. Awaiting a first approval 🤞
While the FDA continues to review Ultragenyx’s UX111 Type A gene therapy application for accelerated approval, we are hopeful that no news is good news and they are working hard to finalize necessary steps. Many of you continue to reach out to legislators and share your stories about how meaningful timely access to UX111 is for your child. Your advocacy and voice about the lived experience with Sanfilippo continues to be important and impactful. While the planned FDA response date of Sept. 19 can’t come soon enough (and of course we hope to hear sooner!), the Cure Sanfilippo team has begun preparations to support families navigating access in hopes of a positive FDA decision. This is an exciting but still uncertain time, and we are here to walk with you every step of the way. We want to hear from you and what you’re thinking. Reach out anytime at Contact@CureSanfilippoFoundation.org.