Cardiovascular Disease

HanAll has developed an innovative approach in the development of cardiovascular Fixed Dose Combination (FDC) products capitalizing the concept of time release formulation and chronotherapy. The concept is to maximize the pharmacological properties of the individual therapies but avoiding metabolic hurdles in developing new combination products. Taking advantage of the PK characteristics of each product, the key to HanAll’s “XC” hybrid combination technology is to avoid unwanted side-effects by reducing/avoiding drug-drug interactions and maximize efficacy by regulating the order and time of release and absorption of each combined drug. The potential superiority of “XC” hybrid formulation technology over simple combination or concurrent cardiovascular therapy has been studied in preclinical and pilot, proof of concept studies in human conducted by HanAll.

Current combination products are the simple fixed combination of more than two different products in one tablet or capsule and, thus, have the limitations of dosage inflexibility, possible drug-drug interactions due to simultaneous release and absorption, reduced efficacy and side effects, and other shortcomings compared to monotherapy. Moreover, the pharmacological characteristics of combined drugs which undergo liver metabolism (Cytochrome P450) may compete for the same enzyme, thus altering the desired and optimal PK/PD profile for each agent. Furthermore, drug-drug interactions at various transporters may also affect PK/PD profile.

HL040 (Atorvastatin + Losartan)

HL040 combination product is composed of atorvastatin and losartan for the treatment of Hyperlipidemia and hypertension. Atorvastatin is CYP450 3A4/3A5 substrate whereas losartan in this case is CYP3A4/3A5 inhibitor relative to atorvastatin. Thus, atorvastatin will be released first followed by losartan to minimize the drug-drug interactions. HanAll recently completed phase I trial (4x4 crossover) in Korea comparing against co-administration of two single drugs and its results showed that HL040 exhibited lower atorvastatin level compared to the co-administration, indicating that it reduced the drug-drug interactions. Moreover, its atorvastatin concentration was close to monotherapy level, indicating that HL040 almost avoided drug-drug interactions. Thus, it is anticipated that HL040 will reduce adverse drug events of atorvastatin such as myalgia and myopathy with long term use.

HL040 project is also partly supported by the Korean Government and HanAll has completed phase I trial and completed phase III patient recruitments. Moreover, phase II trial is initiated in the US.

Other FDCs in Development

Code Drug A Drug B Development Status
HL063B Chlorthalidone Telmisartan P3 on-going
HL068 Candesartan Amlodipine P3 on-going
HL172 Metformin HCl Candesartan P1 completed