Tovorafenib's approval in Europe and around the world: How long will you have to wait?

Low-grade gliomas (LGG) account for about two-thirds of all tumors in children. In most cases, they are highly treatable and curable - either with surgery or with chemotherapy. However, about 20% of patients with LGG have a BRAF gene mutation, which can make the tumor more aggressive and stubborn.

With the FDA's recent approval of Ojemda (tovorafenib), a milestone was reached for LGG patients. Tovorafenib is the first treatment to date that is specifically focused on pediatric low-grade gliomas with BRAF mutations. 

While this is good news, what does it mean for patients outside the USA? Here's everything you need to know about tovorafenib's EMA approval, MHRA approval, and its expected availability in other countries. 

What is tovorafenib used for?

Ojemda (tovorafenib) is indicated for the treatment of relapsed or refractory pediatric low-grade glioma (GLL) in patients who are at least 6 months old. The medicine is specifically designed for LGG cases where a BRAF fusion, rearrangement, or the BRAF V600 mutation are present ¹. 

Tovorafenib is a type II RAF inhibitor. It penetrates the central nervous system and inhibits a protein called BRAF. BRAF is involved in cell signaling, in both its single and double forms. Unlike some other drugs in its class, tovorafenib does not accidentally activate a key signaling pathway known as MAPK ². 

What is tovorafenib's success rate in clinical trials?

Tovorafenib's accelerated FDA approval was based on the results of the Phase 2 FIREFLY-1 trial. The trial is still ongoing and includes patients across 11 countires, aged 6 months to 25 years, and with pretreated LGGs that are growing ³.

The trial's key reported results were:

• 51% of patients had their tumors decrease in size;
• The median time to response was 5.3 months;
• The median duration of response was 13.8 months;
• The most common adverse effects were hair color changes, tiredness, rashes, and dry skin;
• The most common serious adverse effects included decreased growth rate, decreased appetite, vomiting, and tumor hemorrhage ³.

A further, phase 3 trial (LOGGIC/FIREFLY-2) is ongoing and is comparing tovorafenib with chemotherapy in the treatment of newly diagnosed patients with LGG and a RAF mutation. 

Is tovorafenib approved somewhere?

Yes, the medicine was granted accelerated FDA approval in April 2024. As of June 2024, tovorafeib isn't approved anywhere else in the world.

When will tovorafenib get EMA approval?

As of June 2024, there is no marketing authorization application submitted to the EMA for tovorafenib. That makes it difficult to provide an approval timeline estimate. Typically, EMA approval decisions take up to 210 days. Therefore, if an approval application for Ojemda is submitted soon, we would be looking at a possible EMA approval around mid-2025. However, this is only a theoretical possibility, as no application has been filed yet. 

When will tovorafenib be available in Europe?

Approval and availability are two separate topics. Even in the best-case scenario, where tovorafenib gets EMA approval around mid-2025, it still won't be available across Europe immediately. 

Each EU member state launches EMA-approved medicines at their own pace. Some, like Germany, are relatively quick, with an average launch time of 100 days for oncological treatments. At the other end of the spectrum is Romania, where it takes an average of 964 days for a new cancer treatment to become available ⁴.

In other words, tovorafenib could theoretically become available in some EU coutries towards the end of 2025. That's all depending on a marketing authorization application being submitted within the second half of 2024. Other countries in Europe may be facing an additional couple of years of waiting time. 

When will tovorafenib get approval in the UK?

As of June 2024, there is no marketing authorization application submitted to the MHRA for Ojemda (tovorafenib).

However, this doesn't have to mean it will take longer for the medicine to get MHRA approval than approval elsewhere. According to post-Brexit regulations, the MHRA can approve medicines locally as soon as they get the green light from another trusted regulatory body (such as the EMA or FDA). This is known as the International Reliance Procedure ⁵. The MHRA could decide to take this road for approving tovorafenib.

When will tovorafenib be available to UK patients?

If the MHRA approves Ojemda soon, on the basis of its FDA approval, the medicine will then require a NICE assessment before becoming available on the NHS. If approved, the medicine should be available to UK patients within three months of the NICE's decision date.

Assuming a best-case scenario, where the MHRA adopts tovorafenib's FDA approval by the end of 2024, and NICE makes a positive decision soon after, Ojemda could be available in the UK by mid-2025. However, note that this is only a theoretical timeline and the MHRA's actions in the next months will determine whether it's realistic.

How to get tovorafenib before it's approved in your country

If you're based outside the USA, having to wait for tovorafenib's local approval may be discouraging. Fortunately, you may have options other than waiting. Instead, your child's doctor and you could consider a clinical trial. Or, buying and accessing Ojemda via Named Patient Import.

Join a tovorafenib clinical trial

One way to access Ojemda quickly is to enroll in a clinical trial. This can often be easier said than done, as you and your child's doctor would need to find a trial that is currently recruiting participants in your country. Your child would also have to meet their eligibility criteria and accept the risk that they may be assigned to the control group in the trial.

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

• ClinicalTrials.gov: This is a database with all clinical trials in the USA. Some of the trials are also open to international participants. An example is the LOGGIC/​FIREFLY-2 clinical trial, which is open to patients in multiple countries ⁶.
• EUClinicaltrials.eu: This is a database with 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.
• myTomorrows: This organization supports patients in finding treatment options in clinical trials.

Tovorafenib expanded access

Ojemda (tovorafenib) may be available to patients outside the USA under specific conditions, according to Day One's expanded access program. To find out if your child is eligible, get in touch with Day One directly. 

Buy tovorafenib via Named Patient Import

Are clinical trials or the manufacturer's expanded access program not an option? Then there is more way to get the medicine your child needs before it's approved locally.

In most countries, patients are legally allowed to buy and import medicines that could enhance their quality of life or address life-threatening conditions. The regulation making this possible is known as Named Patient Import.

There may be variations across countries in terms of the specific administrative requirements. However, in all cases these criteria must be met:

• The medicine in question has market approval in another country and is not (yet) approved or available in the patient's country;
• There is no alternative on the local market;
• The medicine is for personal use;
• The patient has a prescription from their treating doctor;
• The doctor takes responsibility for the treatment. This might require different documentation from country to country.

Do you want to use the Named Patient Import regulation to get Ojemda before its EU approval (or its approval in the UK or elsewhere)? You will first need to consult your child's treating doctor and get a suitable prescription.

Already have a prescription? Our team can support you with buying tovorafenib immediately. Get in touch with us for more information.

References:

1. HIGHLIGHTS OF PRESCRIBING INFORMATION. Accessdata.fda.gov, Accessed 25 June 2024.
2. Tovorafenib Presents Opportunity for Tumor Reduction in Pediatric Low-Grade Glioma. OncLive, 4 June 2023.
3. Study to evaluate the safety and efficacy of tovorafenib in pediatric patients with relapsed/recurrent low-grade glioma: updated results from the FIREFLY-1 study. Day One Clinical trials, Accessed 25 June 2024.
4. EFPIA Patients W.A.I.T. Indicator 2021 Survey. EFPIA, Accessed 25 June 2024.
5. Fast-Tracking Approval of Medicines - UK Publishes Detailed Guidance on its New International Recognition Procedure. Inside EU Life Sciences, 11 September 2023.
6. DAY101 vs. Standard of Care Chemotherapy in Pediatric Patients With Low-Grade Glioma Requiring First-Line Systemic Therapy (LOGGIC/​FIREFLY-2). ClinicalTrials.gov, Accessed 25 June 2024.