Kizfizo® / Kimozo® (non-approved product)

    Kizfizo® (code names: Ped-TMZ or Kimozo)

    Temozolomide oral suspension, 40mg/ml
    Product under registration dossier review in the EU for the treatment of relapsed or refractory neuroblastoma.

    Kimozo® was the intended trademark, however it was rejected by the European Medicines Agency which identified a risk of confusion in speech, print or handwriting with some products locally approved in certain European countries. Then, Kizfizo® was selected by Orphelia Pharma and approved by the EMA as a suitable trademark for the product. Kizfizo® will be used when the product is approved, whereas early access programs of the product will keep the name Kimozo® untill final regulatory approval. Ped-TMZ was the code name of the product during its development.

    Kizfizo 40 mg/ml is a ready-to-use and taste-masked oral suspension of temozolomide.

    Kizfizo is bioequivalent to temozolomide capsules (Temodal®) as demonstrated by Ducray et al., ASCO 2022 (Abstract, Poster).

    Pharmaceutical form

    Kizfizo is presented in a kit containing 1 bottle filled with 18 ml of temozolomide oral suspension (40mg/ml) and 1 dosing oral syringe graduated up to 5 ml with a 0.1 ml dosing increment.

     

    Targeted indication

    Kizfizo is not approved yet.

    ORPHELIA Pharma is developing Kizfizo in monotherapy or in combination with a specific DNA inhibitor topoisomerase I (irinotecan or topotecan) for the treatment of patients aged 12 months and above with:

    • refractory neuroblastoma or presenting an insufficient response to induction chemotherapy,
    • recurrent neuroblastoma after at least partial response to induction chemotherapy followed by myeloablative therapy and stem cell transplantation

    Unmet medical need in pediatric patients

    Kizfizo is intended for the treatment of relapsed and refractory neuroblastoma, a pediatric cancer of dismal prognosis. Kizfizo is an oral suspension of temozolomide, which is part of the EU and US standard salvage therapy for these highly vulnerable patients(1-3).

    Given the very young age of the neuroblastoma patients (the median age at diagnosis is 18 months), Kizfizo has been specifically developed as a liquid, ready-to-use and taste-masked oral suspension to fully address the needs of this patient population in line with EMA recommendations(4,5).

    Orphan designation

    Kizfizo has received orphan designation for the treatment of neuroblastoma in Europe(6) and in the US(7).

    Clinical development

    Kizfizo(Ped-TMZ/Kimozo) has completed its clinical development program, which includes:

    1. The “Bioequivalence Study Between Temozolomide Oral Suspension (Ped-TMZ) and Temodal® Capsules” is an open label, randomized, crossover, multi center, 2-period study in 30 male/female adult patients with primary CNS malignancies. The study demonstrated bioequivalence between Kizfizo and Temodal® (NCT04467346, completed).
    2. TEMOkids is a pharmacokinetic, acceptability and safety study in pediatric patients aged 1 to less than 18 years, in need of temozolomide. It is an international open-label, non-randomized, prospective, single-arm phase 1 study to determine the pharmacokinetic (PK), the acceptability and the safety of Kizfizo/Kimozo in the pediatric population. You can visit the platform clinicaltrials.gov for more details (NTC04610736).

    In addition, the clinical evidence of safety and efficacy of temozolomide in relapsed or refractory neuroblastoma as part of the registration dossier, is supported in particular by:

    1. Beacon-chemo, a sub-analysis of the chemotherapy arms (temozolomide monotherapy or in combination with irinotecan or topotecan) of the randomized, prospective, BEACON phase 2 study (NCT02308527), assessing efficacy and tolerability of TMZ in 80 pediatric patients.
    2. RetroTMZ, a retrospective study in 6 centers in 3 countries (France, Spain, Switzerland) with 196 children with refractory or relapsed high-risk neuroblastoma diagnosed between 2004 and 2017, followed-up to 02/02/2021, and receiving single-agent or combined TMZ, assessing efficacy and tolerability of TMZ (MR004 N° 2207313).

    Expanded access program (under the name Kimozo)

    France:

    Kimozo received an Autorisation d’Accès Précoce (AAP) for the treatment of
    patients aged 1 to 6 years of age and in patients older than 6 years of age,
    who are unable to swallow temozolomide in capsule form suffering with
    relapsed or refractory neuroblastoma in March 2022.

    Kimozo may also be available upon named patient approvals from French Authorities (ANSM) for other rare solid pediatric cancers under the Autorisation d’Accès Compassionnel (AAC) scheme, in patients aged 1 to 6 years of age and in patients older than 6 years of age, who are unable to swallow temozolomide in capsule form.

    Please visit ansm.sante.fr for more information.

    Europe:

    ORPHELIA has partnered with Tanner Pharma Group to facilitate named patient access to Kimozo in Europe. Please refer to KIMOZO Flyer or ask for more information at: kimozo@tannerpharma.com

    Bibliography

    • Ducray et al., A bioequivalence study of a novel liquid and ready-to-use temozolomide oral suspension and temozolomide capsules inpatients with primary central nervous system malignancies, ASCO 2022 congress: Abstract and Poster
    • Lemarchand et al., Dispensing oral temozolomide in children: precision and stability of a novel and ready-to-use liquid formulation in comparison with capsule-derived mixtures, SIOP 2022 congress: Abstract and Poster
    • Annereau et al., Development of a Hospital Compounded, Taste-Masked, Temozolomide Oral Suspension and 5-Year Real-Life Experience in Treating Paediatric Patients, Pharmaceuticals, 2022.
    • Metayer et al., SIOP 2019 Abstract (Temozolomide as a single agent or in combination for patients with high-risk refractory or relapsed neuroblastoma: excellent tolerance and sustained disease responses)

    References

    1. Children’s Cancer and Leukaemia Group, Options for the Treatment of Patients with Relapsed/Progressive High-Risk Neuroblastoma, March 2015 (accessible online)
    2. Parikh, N.S., et al., Pediatr Blood Cancer, 2015
    3. Moreno, L., et al., Pediatr Blood Cancer, 2017
    4. Formulations of choice for the paediatric population (EMEA/CHMP/PEG/194810/2005)
    5. Draft inventory of paediatric therapeutic needs: Paediatric oncology (EMA/PDCO/381728/2014)
    6. Orphan Drug Designation EU
    7. Orphan Drug Designation US