Unlocking the True Potential of Antibody Drug Conjugates

The success of Adcetris and Kadcyla is paving the way for more antibody drug conjugates to enter the market, especially in the treatment of solid tumors.
Oct 17, 2013

While the long-term future of antibody drug conjugates (ADC) market is difficult to predict, the outlook over the next few years is promising. The total market value of ADCs has been projected to be worth $10 billion by 2023.

The advantages of ADCs due to their ability to offer targeted delivery and therefore reduce side effects of cancer therapies have revolutionized the field of oncology, which can be seen with the recent approvals of Adcetris (brentuximab vedotin) and Kadcyla (ado-trastuzumab emtansine). Many pharma and biotech players are now investing more heavily in ADCs.

Vijay Shah, executive director and chief operating officer of Piramal Enterprises, noted in the first part of the CPhI Worldwide and CPhI Pharma Evolution annual industry report, released earlier this month, that the failures of ADCs in the past was not due to the lack of specificity but rather the lack of activity. “The cytotoxic agents were simply not active enough to kill the target cell with such a small amount of payload (i.e., o.o1%),” he said. However, Vijay Shah believes novel technologies that improve antibody and antigen conjugation could hold the key to unlocking the their potential and the next decade will see ADCs with much higher penetration rates.

There is still progress to be made in antibody selection, the payload and the linking chemistry to combine the two elements together. Target selection is crucial for a successful conjugate, and the goal is to identify one that is significantly overexpressed on cancer cells but not on healthy cells. The antigen target also needs to be expressed on the cell surface, where it is accessible to the antibody. For an ADC, the antigen needs to be internalized, said Vijay Shah, although this is not a requirement for a radioimmunoconjugate. He noted that this is a key area for research as not all antigens meet these criteria. Nevertheless, we are gradually seeing the light at the end of the tunnel. Today, there is a growing number of companies developing conjugation technologies and linker chemistries, which were once a huge hurdle in the development of ADCs.

Another major challenge lies in the manufacture of these compounds as it involves the handling of biologics and highly potent small molecule toxins. At the moment, only a few CMOs have such manufacturing capabilities. With more ADCs demonstrating positive outcomes in clinical trials, the industry will soon have to find a better solution to address the strain on ADC manufacturing capacity.

The success of the recent commercialized products has paved the way for more ADCs to enter the market. It will not only be limited to cancer treatments but extend to other indications such as inflammation as Vijay Shah pointed out. It has been projected that over the next five years, there will be a 50% increase in the number of IND submissions for ADCs, although the majority of them will be for the treatment of lymphoma for the short term.