CINARIF® is a semi synthetic antibiotic belonging to Rifamycins’ group.
CINARIF® inhibits DNA-dependent RNA polymerase of Mycobacterium tuberculosis. It kills actively multiplying extracellular organisms, intracellular mycobacteria, and semidormant mycobacteria in tissues.
It is created to cure all forms of drug susceptible TB and latent tuberculosis infection (LTBI) but it is expected also to be applicable in some drug resistant cases, and for patients with HIV co-morbidity.
Development started in late 90’s after the development of its predecessors T-9 and T-11.
T-9 and T-11 underwent in vitro and in vivo pre-clinical studies with mice, rats, rabbits and guinea pigs. Pharmacokinetics, acute, subacute and chronic toxicology, embryotoxicity, teratogenicity have been also investigated. One Phase II clinical trial with 60 people has been conducted. All the data are published in scientific magazines and specialized congresses posters. Summarized data about T-9 and T-11 studies could be seen in the article: Experimental and Clinical Studies on Rifacinna® – The New Effective Antituberculous Drug (Review), Recent Patents on Anti-Infective Drug Discovery, 2010, 5, 76-90”
CINARIF® was developed with improved stability of the chemical compound and improved antimicrobial activity as main goals.
CINARIF® showed excellent antimicrobial activity against Mycobacterium tuberculosis, atypical mycobacteria (MAC complex), as well as Gram (+) and Gram (-) bacteria including MRSA.
CINARIF® was shown to be 10 to 30 times more active than Rifampicicn against Mycobacterium tuberculosis in vitro studies.
CINARIF® toxicological profile (proven by acute oral toxicity) is similar to T-9 and T-11. CINARIF® has low acute oral toxicity according to the classification Hodge-Sterner.
CINARIF® is developed in Bulgaria, EU.
Expected advantages of the new product CINARIF® are as follows:
- Shorter treatment– up to 30% reduction of overall treatment duration (from 6 months to 4 months) for both phases which in turn reduces the total treatment cost.
- CINARIF® could be included in all the old and new investigated regimens and schemes for drug susceptible tuberculosis.
- Easy to introduce and apply – CINARIF® belongs to well-known TB drug group (Rifamycins’ group). For the medical specialists is expected be easy to introduce and apply a new therapy with CINARIF®.
- Greater intermittency of application (could be administered in two or three times weekly) compared to Rifampicin. That expected to allow the application in a standard or intermittent regimen to all TB forms and to Latent tuberculosis infection (LTBI).
- CINARIF® is more effective than Rifampicin (based on lower MICs, T-9 and T-11 studies) and as a consequence it could lead to earlier culture conversion. This means earlier stop of the transmission of the infection to healthy people.
- Fewer adverse effects (based on lower MICs data) compared to Rifampicin. The toxicology profile of CINARIF® is similar to other Rifamicines but lower MICs data could allow lower total dosage. It is well known that in Rifamicines most of the adverse effects are dose dependent.
- CINARIF® is active against some resistant TB strains. Rifamycins’ cross resistance is well known. But CINARIF® is active against some Isoniazide resistant and some Rifampicin resistant (RR) TB strains. It could suppress the disease in some of these cases. Applied with other RNAP blockers like AAPs and APYs CINARIF® could be used for wider range of DR TB cases.
- CINARIF® has a very good activity (low MICs) against atypical mycobacteria which are often found in HIV-positive TB patients.
- Price affordability. As an innovative molecule CINARIF® should not be compared with Rifampicin price-wise because Rifampicin is a generic drug produced by more than 230 entities (according to IQVIA data). But it is planned to be comparable to most of other Rifamicicnes in the market which are also generic. CINARIF® is expected to reduce substantially total treatment cost and as a consequence to compensate part of the WHO TB funding gap.
- CINARIF® is easy to produce and deliver to the market. CINARIF® belongs to the group of Rifamicines for which capsules, tablets and fixed dosage forms have been developed a long time ago and would be easily applied to CINARIF® as well.
- 5-7 years to the launch: as most of the details about CINARIF® are clear from the studies done with T-9, T-11 (MICs, PK, toxicology profile, and clinical profile) and CINARIF® (MICs and toxicology profile) all the new studies are needed only to confirm it in order to receive Marketing authorization. The low risk of the investment in CINARIF® is evidence based.
CINARIF® covers most of the WHO requirements for a new TB drug. The shorter and more effective treatment of drug susceptible TB cases is expected to improve patients’ adherence to the therapy and to reduce the number of drug resistance cases.