Jim Cassidy, MD, PhD, chief medical officer at SpringWorks Therapeutics, talked about how the prioritization of mirdametinib, a promising treatment for both adult and pediatric patients with neurofibromatosis type 1-associated plexiform neurofibromas.
Jim Cassidy, MD, PhD
(Credit: SpringWorks Therapeutics)
Neurofibromatosis type 1 (NF1), a rare genetic disorder, stems from loss-of-function variants in the NF1 gene and manifests as a variety of symptoms across numerous organ systems. These symptoms may include abnormal skin pigmentation, skeletal deformities, tumor growth, and neurological complications such as cognitive impairment.1 Mirdametinib (SpringWorks Therapeutics) is a potent, oral, central nervous system (CNS)-penetrant, allosteric small molecule MEK inhibitor in development as treatment for patients with NF1-associated plexiform neurofibromas (NF1-PN).
In recent news, the FDA accepted and granted priority review to SpringWorks Therapeutics’ new drug application (NDA) for mirdametinib in adult and pediatric patients with NF1-PN. The agency has scheduled a PDUFA action date of February 28, 2025, and noted that it does not have current plans to hold an advisory committee meeting to discuss the application. The submission included data from the pivotal phase 2b ReNeu trial (NCT03962543), a multicenter, open-label study that featured 114 patients with NF1 PN (58 adult and 56 pediatric) who received mirdametinib for up to 24 months.2
In addition to having its NDA accepted by the FDA, the company announced that the European Medicines Agency validated the Marketing Authorization Application for mirdametinib for the treatment of adult and pediatric patients with NF1-PN. Following the news, Jim Cassidy, MD, PhD, chief medical officer at SpringWorks Therapeutics, had a conversation with NeurologyLive® to discuss what inspired the company to focus on developing mirdametinib for NF1-PN. He also talked about how mirdametinib differentiates itself from current treatments that are used for NF1-PN, especially regarding administration and safety. Furthermore, Cassidy spoke about the challenges that were faced during the ReNeu trial, and how these overcome to ensure successful patient enrollment.
SpringWorks was founded in 2017 with a mission to reignite promising science for underserved patient populations. When the company was formed, we in-licensed mirdametinib from Pfizer and quickly established the infrastructure and resources needed to prioritize and advance mirdametinib into the pivotal phase 2b ReNeu study. We’ve been working with urgency to bring mirdametinib to the NF community because NF1-PN is a devastating and lifelong disease with substantial needs that are not met by current treatment options.
There is no approved therapy for adult patients, giving mirdametinib the potential to be the first approved therapy for adults with NF1-PN. In addition, while there is an FDA-approved therapy for children, there are challenges with administration and tolerability, so there remains an unmet need among children with NF1-PN.
The results from our phase 2b ReNeu trial, recently presented in an oral presentation at the 2024 American Society of Clinical Oncology Annual Meeting, showed robust efficacy demonstrated by significant objective response rates, deep and durable responses and improvements in pain and health-related quality of life. The data from ReNeu also indicated that mirdametinib has a manageable safety profile. In addition, if approved, mirdametinib will offer convenient dosing, which we view as a potential differentiator from other treatments because the dosing regimen provides a built-in treatment holiday (3 weeks on treatment, 1 week off) and has a pediatric-friendly dispersible formulation.
Clinical trial recruitment for a rare disease can always present recruitment challenges because of the low numbers of people living with each rare disease and a geographically dispersed patient population, with some patients needing to travel significant distances to participate. An additional challenge was recruiting patients for the ReNeu trial during the peak of the Covid-19 pandemic.
That we were able to successfully enroll the study during the height of the pandemic and when the FDA had approved the first treatment for pediatric patients with NF1-PN reinforced for us the high unmet need for both children and adults in this community.
We are grateful for the support from the Neurofibromatosis Network (NF Network) and the Children’s Tumor Foundation (CTF), two patient advocacy organizations, in raising awareness of the ReNeu study, which contributed to enrolling the study in a timely manner.
Another challenge in treating NF1-PN, which was also a challenge in the clinical trial setting, is building the right multi-disciplinary care team. Because NF1-PN can affect the body in different ways, many types of healthcare professionals can help in the management of NF1-PN. In the ReNeu trial, the treating neurologist or oncologist needed to work in close coordination with other specialists, including ophthalmology, cardiology, physical therapy, and others for thorough monitoring and evaluations.
We look forward to working with regulatory authorities on their reviews of our applications for mirdametinib, both in the U.S. and Europe. We are also focused on sharing additional data from the phase 2b ReNeu trial at upcoming medical meetings and expect the data to be published in a peer-reviewed publication later this year. In parallel, we are advancing our preparations in anticipation of a potential launch in early 2025. In the U.S., we recently kicked off a disease education campaign called “Coping Isn’t Care” to educate about NF1-PN and empower patients to advocate for themselves and re-engage in ongoing care. The campaign features websites to help both HCPs and patients with the transition from pediatric to adult care, which can be challenging in this disease area, and aims to educate and empower young adult patients who frequently drop out of care to advocate for themselves and re-engage through better education.
We believe that there is a significant opportunity for mirdametinib to impact the treatment landscape for NF1-PN. There are approximately 40,000 patients with NF1-PN in the U.S. today, the majority of whom are adults who currently do not have an FDA-approved therapy. We believe mirdametinib could allow many more patients to be treated, potentially filling an unmet need that currently exists and making a meaningful impact in these patients’ lives.
Transcript edited for clarity.
