Nidlegy's approval (FDA, EMA, MHRA and more): How long will you have to wait?

Melanoma is a type of skin cancer that affects about 3.4 in every 100,000 people worldwide ¹. Australia and New Zealand have the highest melanoma incidence rate. Right after them on the list are countries in northern and western Europe ².

Currently, if melanoma is locally advanced and can be surgically removed, surgery is the only approved treatment route. However, Nidlegy (daromun) is an investigational neoadjuvant treatment that may help patients get better outcomes after surgery.

As Nidlegy is still in development, here's what you need to know about its reported efficacy, including when its approval is expected around the world.

Nidlegy: the newest treatment for melanoma in 2024

Currently, patients with melanoma that can be surgically removed are treated with surgery, possibly followed by additional approved systemic therapies. However, there is no approved treatment of locally advanced, fully resectable melanoma in the neoadjuvant setting (before surgery).

If approved, Nidlegy (daromun) will be the first neoadjuvant treatment for resectable melanoma, which can be applied before surgery to enhance its outcomes.

How does Nidlegy work for skin cancer?

Nidlegy (daromun) contains two components, L19IL2 and L19TNF, that work together to kill tumor cells and trigger an immune response against the tumor. It's the first cancer treatment approved by the EMA for development as a combination therapy.

Because Nidlegy is intended for administration directly to the tumor site, it may be able to maximize its impact on the cancer cells with minimal systemic side effects. Daromun aims to reduce tumor size and improve outcomes for patients with skin cancers like melanoma.

In addition to melanoma, Nidlegy is also being studied in patients with non-melanoma skin cancers (e.g. basal cell carcinoma and cutaneous squamous cell carcinoma).

How effective is Nidlegy in clinical trials?

In June 2024, Nidlegy's manufacturer, Philogen, announced the initial results from its Phase 3 pivotal study ⁴. In this study, patients were either given Nidlegy followed by surgery, or underwent surgery alone.

The key reporings were:

• Nidlegy reduced the risk of relapse or death by 41% compared to surgery alone;
• The median recurrence free survival was more than doubled with Nidlegy;

• After surgery, adjuvant therapies were required by 29.8% of patients in the Nidlegy group and by 40.5% of the group in the surgery group;

• Nidlegy's safety profile was mostly favorable, with most adverse events being low-grade and localized ⁴.

Shortly after announcing these results, Philogen submitted its application for Nidlegy's EMA approval ³.

In addition to the above trial, there are also other ongoing clinical studies involving daromun, including:Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB/​C Melanoma Patients (NeoDREAM)

• INTACT/MeRCI: This Phase 2 trial focuses on patients with stage III-IV melanoma that cannot be surgically removed and has not responded to previous anti-PD1 therapy. In the study, Nidlegy or each of its active components alone are combined with anti-PD1 therapy. The aim is to establish whether adding (a component of) Nidlegy to existing anti-PD1 treatments may work better than anti-PD1 treatments alone. The study is expected to conclude in 2028 ¹¹.

• DUNCAN: This Phase 2 trial aims to test the effectiveness of injecting daromun directly into tumors in patients with high-risk basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC). The patients involved in the study are either ineligible for surgery or have opted out of it. The study is expected to conclude in September 2024 ⁵.

Is Nidlegy approved somewhere?

As of June 2024, no. The medicine's manufacturer, Philogen, submitted an EMA approval application in June 2024 ³.

Philogen signed an exclusive distribution agreement for Europe, Australia and New Zealand with Sun Pharma in 2023 ⁶. However, the medicine is not yet approved in Australia or New Zealand.

When will Nidlegy get FDA approval?

It's difficult to say, as there is no official approval application submitted as of June 2024. Typically, reviewing an application once it's submitted takes up to 10 months.

When will Nidlegy get EMA approval?

Since Nidlegy's EMA approval application was only submitted in June 2024, there's still some time to go until approval.

First, the EMA needs to validate the application. From that moment on, a review process that can last up to 210 days starts. This timeline may be extended if the manufacturer needs to provide additional information.

With this in mind, Nidlegy (doruman) can theoretically expect to get EMA approval by early 2025.

When will Nidlegy become available in Europe?

Approval is unfortunately not the same as availability. If Nidlegy gets EU marketing authorization in early 2025, it will take each EU member state a different amount of time to launch the medicine locally. Timelines for market launch vary greatly across Europe. Germany tends to be the fastest (100 days on average for oncological medicines) and Romania - the slowest (964 days on average) ⁷.

In other words, Nidlegy may be available in some European countries towards mid-2025, and in others - around 2028.

When will Nidlegy get MHRA approval?

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

However, this doesn't have to mean it will take longer for Nidlegy 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 ⁸. It wouldn't be surprising if the MHRA decides to take this road for approving daromun.

When will Nidlegy become available in the UK?

If the MHRA approves daromun simultaneously with the EMA, expected in early 2025, 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 follows a potential EMA approval in early 2025, and NICE makes a positive decision soon after, Nidlegy could be available in the UK by mid-2025. Only time will tell if such a timeline is indeed realistic.

When will Nidlegy become available in Australia and New Zealand?

As the countries with the highest incidence of melanoma worldwide, it's especially important for patients to know when Nidlegy might be coming to Australia and New Zealand.

As of June 2024, there is no TGA approval application submitted for Nidlegy. As soon as one is submitted, the process of approval and registration can take up to 330 days ⁹.

The situation is similar in New Zealand, but the standard approval process there is a bit shorter - up to 100 days ¹⁰.

Based on the current situation, it seems unlikely that Nidlegy (doruman) will be available to melanoma patients in Australia or New Zealand at least until mid-2025.

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

Depending on where you're based, waiting for Nidlegy to be approved may be a matter of months or years. The prospect of waiting this long may not be an option for all patients. Luckily, you don't have to wait until the medicine is approved in your country. You only need to wait until it's approved somewhere. Then you can access it anywhere else via Named Patient Import (expanded access).

Nidlegy (doruman) expanded access

Even if a medicine is not yet approved or available in your country, you can legally access it. A regulation known as Named Patient Import (expanded access) allows you to buy and import a medicine, as long as it meets these conditions:

• it is approved somewhere;
• it is not approved or available in your country (yet);
• it has no local alternatives, and
• it is for personal use.

This process requires a prescription from your treating doctor. As in all other cases, the doctor assumes responsibility for the treatment. Per country, specific documentation requirements can vary.

Do you want to start your treatment with Nidlegy as soon as possible, using the Named Patient Import regulation? 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. We can support you with buying doruman as soon as it's approved somewhere in the world.

References:

1.  Global Incidence, Mortality, Risk Factors and Trends of Melanoma: A Systematic Analysis of Registries. American Journal of Clinical Dermatology, 10 June 2023.
2. Skin cancer statistics. World Cancer Research Fund, Accessed 18 June 2024.
3. Nidlegy™ Marketing Authorization Application Submitted to EMA. Philogen, 17 February 2021.
4. Efficacy of Daromun Neoadjuvant Intratumoral Treatment in Clinical Stage IIIB/​C Melanoma Patients (NeoDREAM). ClinicalTrials.gov, Accessed 18 June 2024. 
5. Intratumoral Administration of Daromun in Non-melanoma Skin Cancer Patients (DUNCAN). ClinicalTrials.gov, Accessed 18 June 2024.
6. Sun Pharma and Philogen enter into an Exclusive Distribution, License, and Supply Agreement for Commercializing specialty product, NIDLEGY™ in Europe, Australia and New Zealand. BioSpace, Accessed 18 June 2024.
7. EFPIA Patients W.A.I.T. Indicator 2021 Survey. EFPIA, Accessed 18 June 2024.
8. Fast-Tracking Approval of Medicines - UK Publishes Detailed Guidance on its New International Recognition Procedure. Inside EU Life Sciences, 11 September 2023.
9. Prescription medicines registration process. Therapeutic Goods Administration (TGA), 12 August 2021.
10. Evaluation Timeframes and Registration Situation. Medsafe, 7 September 2023.
11. Study of the Efficacy of Intratumoral L19IL2 or L19TNF or L19IL2/L19TNF, in Combination With Pembrolizumab, in Unresectable Melanoma Patients (INTACT/MeRCI). ClinicalTrials.gov, Accessed 18 June 2024.