Zynyz

The medicine can only be obtained with a prescription and treatment should be started and monitored by a doctor experienced in the treatment of cancer.

Zynyz is given once every 4 weeks by infusion (drip) into a vein, which lasts around 30 minutes. Treatment should continue for a maximum of 2 years or until the cancer gets worse. The doctor may interrupt treatment if certain side effects occur or stop it altogether if the side effects are severe.

For more information about using Zynyz, see the package leaflet or contact your doctor or pharmacist.

Zynyz was shown to be effective at clearing the cancer in an ongoing study involving 101 patients with metastatic or locally advanced MCC that came back and could not be cured by surgery or radiation. The study did not compare Zynyz with other medicines or placebo (a dummy treatment).

In the study, around 54% of patients responded to treatment, including around 17% who had a complete response (no signs of cancer) and around 37% who had a partial response (decrease in the extent of cancer). Within the study the patients’ response to treatment lasted on average for 25 months before the disease worsened.

Zynyz received a marketing authorisation valid throughout the EU on 19 April 2024.

For the full list of side effects and restrictions with Zynyz, see the package leaflet.

The most common side effects with Zynyz (which may affect more than 1 in 10 people) include tiredness, rash, diarrhoea, anaemia (low levels of red blood cells), itching, joint pain, constipation, nausea (feeling sick), fever and reduced appetite.

Most of the serious side effects are related to the medicine’s effect on the immune system, such as inflammation in various body organs and tissues, and rash.

At the time of approval there were limited treatment options for patients with metastatic or advanced MCC who cannot have treatment to cure their cancer. In particular, there were no approved therapies for locally advanced MCC that came back. Despite some uncertainties associated with the design of the main study, such as the lack of a comparator medicine, Zynyz was shown to be effective in the treatment of metastatic or locally advanced MCC that has come back and cannot be cured by surgery or radiation therapy.

The side effects seen with Zynyz are mainly related to its effects on the immune system. Overall, the medicine’s safety profile, which is comparable to that of other cancer medicines from the same class, is considered acceptable.

The European Medicines Agency therefore decided that Zynyz’s benefits are greater than its risks and it can be authorised for use in the EU.

The company that markets Zynyz will provide a patient card about side effects affecting the immune system and when and where to seek help if these occur. This card will also inform healthcare professionals that the patient is being treated with Zynyz.

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Zynyz have also been included in the summary of product characteristics and the package leaflet.

As for all medicines, data on the use of Zynyz are continuously monitored. Suspected side effects reported with Zynyz are carefully evaluated and any necessary action taken to protect patients.

The active substance in Zynyz, retifanlimab, is a monoclonal antibody. This is a protein that has been designed to block a target called PD-1 found on certain cells of the immune system (the body’s natural defences). Some cancers can make a protein that attaches to PD-1 and switches off the immune cells’ ability to attack the cancer. By blocking PD-1, retifanlimab was expected to stop the cancer switching off these immune cells, thereby increasing the immune system’s ability to kill the cancer cells.

Zynyz was developed as a medicine to treat adults with squamous carcinoma of the anal canal that had spread beyond the original site. It was intended for use when the cancer had got worse during treatment with platinum-based cancer medicines or when this treatment was not suitable.

Zynyz contains the active substance retifanlimab and was to be available as a concentrate to be made up into a solution for infusion (drip) into a vein.

Retifanlimab was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 19 October 2020 for the treatment of anal cancer.

The company presented results from a main study involving 94 previously treated patients with squamous carcinoma of the anal canal that had spread beyond the original site and whose cancer had got worse on platinum-based therapy or who could not be given this treatment. The main measure of effectiveness was the number of patients who responded to treatment. The study did not compare Zynyz with any other cancer medicine.

The application was withdrawn after the European Medicines Agency had evaluated the initial information from the company and had prepared questions for the company. The company had not responded to the questions at the time of the withdrawal.

Based on the review of the data, at the time of the withdrawal, the Agency had major concerns and its provisional opinion was that Zynyz could not have been authorised for the treatment of squamous carcinoma of the anal canal.

In terms of the main study, the Agency considered that it was not clear whether the number and duration of the responses seen in the study would lead to meaningful benefits for patients such as improvement in survival or living longer without the disease getting worse.

In addition, the Agency noted that the wording of the indication proposed for Zynyz might allow use in previously untreated patients who cannot be given platinum-based therapy, while this group of people was not represented in the study.

Therefore, at the time of the withdrawal, the Agency’s opinion was that the company had not provided enough data to support the application for conditional marketing authorisation of Zynyz.

In its Withdrawal letter: Zynyz notifying the Agency of the withdrawal of the application, the company stated that they were not able to satisfactorily address the Agency’s concerns at this time.

The company informed the Agency that there are no consequences for patients in clinical trials using Zynyz.

If you are in a clinical trial and need more information about your treatment, speak with your clinical trial doctor.