Mirdametinib's approval worldwide: When is the new NF1 treatment coming to you?

Neurofibromatosis Type 1 (NF1) affects about one in every 3,000 people. It can be inherited and symptoms can start as early as childhood. While there is no cure for NF1 (yet), the condition has been managed with a variety of therapies, none of which specifically designed for it. The first FDA-approved treatment specifically for NF1 was Koselugo (selumetinib). The next one is expected to be mirdametinib. These developments offer hope for better and more targeted management of the disease in the future.

While mirdametinib's approval is not a fact yet, it seems to be a matter of time. Here's what you should know about the timelines for FDA, EMA, MHRA approval, and more. 

What is mirdametinib?

Mirdametinib is an investigational medicine that inhibits MEK1 and MEK2 - proteins involved in cell growth. It's being studied for treating neurofibromatosis type 1 (NF1) and low-grade glioma (LGG), especially with overactive MAPK/ERK signaling. The medicine is being tested for use in both adults and children ¹. 

Does mirdametinib cross the blood brain barrier?

Yes, mirdametinib has been shown to cross the blood-brain barrier. This makes it potentially applicable to treating brain metastases ². 

Mirdametinib vs selumetinib: What's the difference?

The recently approved Koselugo (selumetinib) is a similar medicine to mirdametinib. Both are MEK inhibitors. However, they are not identical in administration, efficacy or safety. Some of the differences between them are:

• Ease of administration: Patients taking selumetinib must not eat for 2 hours before and 1 hour after taking a dose. In contrast, mirdametinib's formulation is independent of food intake. Studies on mirdametinib also include a formulation for children who cannot swallow a capsule, making it overall potentially easier to take ³. 
• Applicability: While selumetinib is only approved for use in children, mirdametinib is seeking approval for use in both pediatric and adult patients ⁴. 

Mirdametinib vs trametinib: What's the difference?

Trametinib is another MEK inhibitor that works in a similar way to mirdametinib and selumetinib. However, the main difference between the two medicines is that trametinib is approved for treating melanoma and non-small cell lung cancer. 

A meta-analysis published in 2022 indicates a good potential for trametinib in controlling tumor progression in NF1-related plexiform neurofibromas (pNFs) and low-grade gliomas (LGGs) ⁵. However, trametinib is not currently approved anywhere for this indication. 

What is mirdametinib's success rate in clinical trials?

When the FDA granted priority review to mirdametinib in August 2024, it did so on the basis of the Phase 2 ReNeu trial [6]. The main reported results from this trial include:

• 41% of adult patients and 52% of pediatric patients responded to the treatment (either partially or completely);
• The median time to response was 7.8 months in adults and 7.9 months in children;
• 62% of adults and 52% of children who responded to the treatment achieved a >50% reduction in tumor volume;
• The median best change in tumor volume was -41% in adults and -42% in children;
• Mirdametinib was well tolerated, with most adverse events being mild ⁷.

When will mirdametinib get FDA approval?

When granting mirdametinib priority review, the FDA set a decision date for February 28, 2025 ⁶. Of course, there is no guarantee that the decision will be positive. However, given the clinical trial data available so far, FDA approval appears to be the most likely outcome. 

When will mirdametinib get EMA approval?

In September 2024, the EMA accepted mirdametinib's application for marketing authorization ⁸. Typically, a decision for EMA approval can take up to 210 days. If it results in a positive recommendation, the approval becomes official within 67 days later. In other words, we're looking at a potential European approval for mirdametinib around July 2025. 

When will mirdametinib be available in the UK?

As of September 2024, there is no active application for the MHRA approval of mirdametinib. However, this doesn't have to mean that patients in the UK will have to wait longer for approval than those in the USA or the EU. After Brexit, UK legislation allows for almost simultaneous approval of medicines after another trusted agency (e.g. the FDA or EMA) has given them the green light. It's theoretically possible that the MHRA uses this legislation to move fast on mirdametinib's approval in the UK. However, only time will tell if this is indeed the MHRA's intention. 

How to access mirdametinib before it's available in your country

Even with potential approvals coming to the EU and UK in 2025, mirdametinib will not be available to all patients at the same time. If your treatment cannot wait, you should know that you don't have to. There are ways to access mirdametinib before it's officially available in your country. One option is to find and join a clinical trial. Another is to purchase mirdametinib for personal use as soon as it is approved somewhere in the world (and you have a prescription for it). 

Join a clinical trial

To get quick access to the newest NF1 treatment, you can try joining an ongoing clinical trial. To do so, you must meet the eligibility criteria. You will also need your treating doctor's support. Good to keep in mind is that a trial doesn't guarantee you will be assigned to the treatment group. You may receive placebo instead.

Here are some good places to start looking for ongoing clinical trials:

1. ClinicalTrials.gov: This is a database with all clinical trials in the USA. However, some of the trials are also open to international participants as well. At the moment, these mirdametinib trials are recruiting patients worldwide. They may be worth keeping an eye on.
2. EUClinicaltrials.eu: This database contains all clinical trials in the European Union. Currently, it contains limited information on trials launched before 31 January 2022. For those trials, you can refer to the EU Clinical Trials Register.
3. myTomorrows: This organization supports patients in finding treatment options in clinical trials.

Buy mirdametinib for personal use

Patients worldwide are legally allowed to buy and import medicines for personal use, if they could improve their lives or address life-threatening conditions. Specifically if these medicines are not approved or available locally yet.

If you want to access mirdametinib before it's approved in the USA, Europe and the UK (or where you are located), this might be an option for you and your doctor. The regulation that makes this possible is known as Named Patient Import. Under this regulation, patients can import a medication not yet approved or available in their country if:

• it is approved elsewhere;
• it has no local alternatives, and
• it is for personal use.

This process requires a prescription from your treating doctor. And you can only make use of it after mirdametinib has approval somewhere in the world (wherever that may be). Other documentation requirements may apply, depending on your country.

Do you want to use the Named Patient Import regulation to get mirdametinib before its FDA, MHRA or EMA approval? You will first need to consult your treating doctor and get a suitable prescription.

Already have a prescription? Share it with our team at Everyone.org, so we can support you with buying mirdametinib as soon as it gets its first global approval. Wherever that may be.

References:

1. Stewart, Judith. Mirdametinib: What is it and is it FDA approved?, Drugs.com, Accessed 17 September 2024.
2. What is Mirdametinib used for?, Synapse, Accessed 17 September 2024. 
3. Update on NF1 Research from SpringWorks Therapeutics. Children's Tumor Foundation, 25 May 2021.
4. Adams, Ben. SpringWorks kicks off 'Coping isn't Care' campaign ahead of potential new drug approval. Fierce Pharma, 16 May 2024.
5. Efficacy and Safety of Trametinib in Neurofibromatosis Type 1-Associated Plexiform Neurofibroma and Low-Grade Glioma: A Systematic Review and Meta-Analysis. NCBI, 31 July 2022.
6. Mirdametinib Scores FDA Priority Review in Neurofibromatosis Type 1 With PN. Targeted Oncology, Accessed 17 September 2024. 
7. SpringWorks Therapeutics Announces Data to be Presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. SpringWorks Therapeutics, 23 May 2024.
8. FDA grants Priority Review to NDA for mirdametinib for the treatment of adults and children with neurofibromatosis type 1-associated plexiform neurofibromas. Springworks Therapeutics, Accessed 17 September 2024.