Europe Rejects Cinainu (Alopecia) & Kizfizo (Neuroblastoma)

Europe’s Committee for Medicinal Products for Human Use (CHMP) has recommended refusal of marketing authorizations for:

• Cinainu (allium/citrus/Paullinia/cacao), an herbal medicine intended to treat moderate to severe alopecia areata in children and adolescents
• Kizfizo (temozolomide) for the treatment of neuroblastoma in children older than 1 year

Herbal Extracts

Cinainu contains herbal extracts of onion, lemon, guarana, and cocoa, and was intended to be available as a solution for skin application. Its precise botanical composition is:

• Liquid ethanolic extract 30% (W/W) of Allium cepa fresh bulb and citrus limon fresh fruit
• Dry aqueous extract of Paullinia cupana seed, also known as guarana
• Dry hydroethanolic extract of Theobroma cacao seed

The applicant, Legacy Healthcare (France) S.A.S., presented results of a study in 107 children aged 2-17 with moderate to severe alopecia areata affecting between 25% and 95% of the scalp. They were treated with twice-daily sprays of Cinainu or a placebo for 24 weeks, looking for improvements in the SALT score, a standard rating score for alopecia. However, study results “did not show that the medicine was effective in treating moderate to severe alopecia areata,” the CHMP said. Moreover, the company had not shown conclusively that the medicine used in the main study was comparable to the one it intended to place on the market.

Also, while it was suggested that Cinainu could reduce cell death and scalp inflammation, and influence different phases of the hair growth cycle, the way it works “is not clear.” The CHMP had other concerns about the study, including that a relatively small proportion of participants were included in the final analysis presented to the agency. The company had not provided sufficient safety data from laboratory studies, such as toxicity studies, for the intended long-term use. Finally, there were problems related to quality control, stability of the medicine, and the risk for impurities.

Therefore, the committee’s opinion was that the benefits of Cinainu did not outweigh its risks and it recommended refusing marketing authorization. The company may ask for a re-examination within 15 days of receiving the opinion on November 14.

Neuroblastoma Treatment Refused 

The CHMP also recommended refusal of Orphelia Pharma’s application for marketing authorization for Kizfizo (temozolomide), which had been intended for the treatment of high-risk neuroblastoma in children older than 1 year, as combination therapy with either irinotecan or topotecan. The application specified use in children whose neuroblastoma had not improved with chemotherapy or had recurred after chemotherapy and stem cell transplantation.

In 2019 Kizfizo had been designated an “orphan medicine” for neuroblastoma. It was developed as a hybrid medicine, similar to a reference medicine, Temodal (Merck Sharp & Dohme), containing the same active ingredient. Temozolomide is an alkylating agent metabolized in the body to its active form monomethyl triazenoimidazole carboxamide, which is cytotoxic and thus expected to slow down tumor growth.

The CHMP explained its refusal on the basis that the proportion of patients who responded to temozolomide plus irinotecan or topotecan was “too modest to show that it is beneficial,” on account of the company’s presented clinical study, involving 102 patients up to 21 years of age with neuroblastoma, or an observational study also presented. The CHMP said it was not possible to determine the effect of temozolomide on the basis of the data from these studies. Therefore, the balance of benefits and risks of Kizfizo to treat children with neuroblastoma could not be established.

Dr Sheena Meredith is an established medical writer, editor, and consultant in healthcare communications, with extensive experience writing for medical professionals and the general public. She is qualified in medicine and in law and medical ethics.