The European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) has recommended refusing marketing authorization for three investigational therapies for cancer and transplant-related conditions: Tacquell (autologous melanoma-derived tumor infiltrating lymphocytes, ex vivo-expanded; Netherlands Cancer Institute), Yartemlea (narsoplimab; Omeros Ireland Limited), and Xervyteg (allogeneic fecal microbiota, pooled; MaaT Pharma).

All three applications were reviewed during the June 2026 CHMP meeting, with the committee concluding that the benefit-risk balance could not be established for any of the products based on the submitted clinical and manufacturing data. Their intended indications were:

• Tacquell for advanced, metastatic melanoma
• Yartemlea for adults and children aged 2 years or older with hematopoietic stem cell transplant-associated thrombotic microangiopathy
• Xervyteg for acute graft-vs-host disease

The applicants may request reexamination within 15 days of receiving the opinions.

Tacquell 

Tacquell, an advanced therapy medicinal product consisting of ex vivo-expanded autologous melanoma-derived tumor infiltrating lymphocytes, was intended for adults with unresectable stage IIIC-IV melanoma previously treated with a PD-1-blocking medicine. The treatment involves collecting white blood cells from a metastasis removed from the patient, expanding them in the laboratory, and reinfusing them as a single intravenous dose following preparatory chemotherapy and subsequent interleukin-2 administration.

The pivotal study included 168 patients and compared Tacquell with ipilimumab, using progression-free survival as the primary endpoint. However, the CHMP identified critical concerns regarding data integrity following a good clinical practice inspection, including deficiencies in traceability and reliability of clinical data. 

Additional issues were noted with the study design, statistical interpretation, and incomplete safety datasets. The manufacturing review also identified concerns related to quality control strategy, batch comparability across production sites, and incomplete documentation of good manufacturing practice. As a result, the CHMP concluded that the efficacy and safety evidence were not sufficiently robust to support authorization.

Yartemlea 

Yartemlea, a monoclonal antibody targeting MASP-2 in the complement pathway, was developed for high-risk hematopoietic stem cell transplant-associated thrombotic microangiopathy in adults and children aged 2 years or older. This serious complication occurs when transplant-related treatments damage small blood vessels, causing blood clots and organ damage.

The company submitted results from a study involving 28 adults without placebo or an active comparator, measuring platelet levels and lactate dehydrogenase changes as markers of disease activity. Additional data came from an expanded access program involving 27 adults and 16 children.

The agency concluded that the evidence was insufficient because the uncontrolled study design prevented assessment of whether observed benefits resulted from Yartemlea, concurrent medications, or other factors. Study conduct concerns included protocol modifications, measurement issues, and dose selection problems. Pediatric data were inadequate for dose assessment and safety evaluation. The study results also did not confirm how the medicine is expected to work in this condition.

Xervyteg 

Xervyteg, an allogeneic fecal microbiota product derived from pooled healthy donors, was intended for patients with acute graft-vs-host disease of the gastrointestinal tract in whom corticosteroids and ruxolitinib had not worked well enough. The therapy aimed to restore gut microbiota balance, reducing inflammation and symptoms such as diarrhea. A 67-patient study examined response rates after treatment but lacked a control group. The agency found that the open-label, uncontrolled design made it impossible to distinguish treatment effects from natural disease progression or concurrent therapies, preventing reliable safety and effectiveness evaluation. In addition, safety attribution remained uncertain, particularly regarding infectious complications. The data also did not clearly show how the medicine works in relation to the observed effects.

The CHMP concluded that neither efficacy nor safety could be reliably determined.

Next Steps 

For Tacquell, the EMA said patients in hospital exemption programs should continue to be managed by their treating clinicians. For Yartemlea and Xervyteg, the applicants informed the agency that the refusals have no consequences for patients in clinical trials or in compassionate, expanded, or other access programs.

Each application remains eligible for reexamination upon request by the respective applicants before a final European Commission decision is issued.