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Thousands years ago, we started the battle against various diseases using different modalities of medicine, including herbs, use of endangered animals, and even some magic-based medicine. With more than 200 years of history, The New England Journal of Medicine has recorded the trials and breakthroughs of modern medicine which significantly improves not only the life span but also the life quality of human beings. In the last few decades, with progress in organic and synthetic chemistry, small molecule medicine has saved thousands of hundreds of lives. More recently, notable breakthroughs in basic biology for example in the fields of Immunology and Development, have led to many blockbuster biologics medicine for cancer, autoimmune diseases and inflammation.
Looking into the future, diseases are more and more complicated and heterogeneous. Single medicine will have limited curing effects and can only treat a portion of patients. Notably, only about 25 percent patients respond to the historical anti-PD1 therapeutics. As quoted by Dr. Michael Varney, Executive Vice President, Genentech Research and Early Development, “One thing we are pretty sure in the next five years of R&D is that there will be more and more modalities of medicine.” Taking the second-most prevalent blood cancer multiple myeloma as an example, many different modalities of medicine have been developed or are under development to battle this life-threatening disease, including small molecules (e.g. bortezomib and carfilzomib), antibodies (e.g. daratumumab against CD38 and elotuzumab against CD319), antibody-drug-conjugate (e.g. GSK2857916 against B Cell Maturation Antigen), cell therapies (e.g. LCAR-B38M and bb2121 against B Cell Maturation Antigen), and many combination of those modalities.
Different modalities of medicine have distinct drug profiles and mechanism of action (MOA), which will bring specific benefits and challenges to patients, as well as to those biopharmaceutical and biotech companies who are developing these drugs. Gene therapy, the “once-for-ever” medicine, has completely reversed the deficiency of several rare genetic diseases. However, besides the world most expensive medicine, the long-term off-target safety concern of gene therapy is still to be evaluated. After the approval of two cell therapies in 2017 by FDA, they have changed the landscape of objective response rate for many blood cancer types (e.g. 91 percent of LCAR-B38M for multiple myeloma). But on the other hand, to date, cell therapy is mainly effective in blood cancer types with limited progress in solid tumor. Also, the highly personalized process development of cell therapy makes the medicine very expensive (e.g. $475K and $373K for the two approved cell therapies). Even though bispecific antibodies hit many bumps in the early days due to intrinsic toxicity of anti- CD3 effect, many breakthroughs have been achieved recently with the expansion of MOA, and technologies in making the new modalities. It is clear that for those most metastatic cancer types with poor prognosis, multiple MOAs and effector cells will be needed to battle against them, including T cells, natural killer cells, and macrophages. In this concept, multi-specific antibodies or fusion proteins will be another new modality for future medicine.
As briefly discussed above, innovative modalities are the trend of future medicine. They are not replacing but complementary to each other. In this way, we are improving the percentage of cured diseases and bring maximal benefits to patients.