A Review of Leukemia Targeting Drugs in 2016: Small Molecule Drugs and Monoclonal Antibody Drugs Par

Leukemia is a clonal disease caused due to mutation of human hematopoietic stem cells, can cause symptoms like bleeding, anemia, organ infiltration and intestinal function failure of patients, and is a human disease of great harm. There is also a big leukemia patient group in China, growing by 30-40 thousand patients every year; the leukemia incidence even tops various tumor diseases among children. It is very urgent that leukemia be effectively treated.

Table 1 Global leukemia targeting drugs

Novartis started early among the leukemia drug developing companies and has been leading in the field. Both the two small molecule drugs against leukemia under Novartis: Imatinib and Nilotinib have been marketed in China. As an oral leukemia drug, Imatinib can be used to treat adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the blast phase and accelerated phase and treat the chronic-phase patients after failure of the interferon therapy. This drug entered the Chinese market early in 2002 and kept growing within more than 10 years, being the preferred drug of most leukemia patients, however, Imatinib’s share has been on a downward trend for Novartis in recent years due to the patent expiration in each country (including China). China approved the marketing of Novartis’ another small molecule drug against leukemia: Nilotinib in 2009, which was approved in the U.S. to go to market in 2007 to mainly treat the newly diagnosed chronic-phase adult patients with Ph+ CML and adult patients resisting to Imatinib.

Besides small molecule drugs, Novartis entered the leukemia biological drug market through acquisition in 2015. Novartis acquired the biological drug Ofatumumab under GSK for USD 1 billion in August 2015, which is a monoclonal antibody (mAb) that can be used in combination with chlorambucil, as a first-line therapy for chronic lymphocytic leukemia patients not suitable for fludarabine.

But Ofatumumab is subject to large competition in sales, as affected by the leukemia mAb drug Rituximab under Roche. As the only biological drug against leukemia in the Chinese market to date, Rituximab has the same target with Ofatumumab, and can have specific binding with CD20 antigen; it was originally a blockbuster mAb drug under Genentech, and became to belong to Roche together with the other two blockbuster mAb drugs: bevacizumab and trastuzumab under Genentech after Roche acquired all equity of Genentech for a price of USD 95 per share in 2009. Those drugs have enabled Roche to come out first in the mAb drug market and take a large market share. Besides, Roche also developed the mAb drug Obinutuzumab and co-developed BCL2 inhibitor Venetociax with AbbVie, in aspect of leukemia drugs. As the first drug that obtained FDA’s breakthrough therapy designation, Obinutuzumab also has obtained the orphan drug designation granted by FDA, and is considered to be better than Rituximab, with very considerable market prospects.

Overall, the current situation of the leukemia drugs is that the small molecule drugs and mAb drugs are paralleling and the two basically have the same quantity. The small molecule chemotherapeutics are mainly "tinib" drugs, wherein, those having entered China include Novartis’ Imatinib and Nilotinib, and BMS’ Dasatinib, while regarding mAb drugs, there is only Rituximab under Roche that has successfully entered the Chinese market, which is possibly because China’s mAb drug market is not mature enough and China is still a developing country where the expensive mAb drugs are difficult to open the market. However, it is certain that there will be more leukemia mAb drugs entering Chinese market, with the rapid development of the bio-medicine of China and the improvement of people’s consumption capacity.