This decade has witnessed significant advances in new cancer treatments, especially via targeted therapeutic pathways. Antibody–drug conjugates (ADCs) present such an approach: the antibody component provides specificity for a tumor target antigen, and the drug confers the cytotoxicity. ADCs or bio-conjugates are also active in many other therapy areas.
Growth in the ADC Market
ADCs have evolved, and the recent third-generation wave has offered reasons for optimism. The technological advances have accelerated the development of ADCs, leading to a drastic increase in the number of clinical trials, especially in solid tumors.
Nearly 202 ADCs and other bio-conjugates have entered clinical trials, of which more than 100 are actively progressing.1 Over 20 new ADCs have been introduced over the last year, a 30% increase. Around 70% of these drugs are in the preclinical/discovery stages. Of the clinical stage candidates, over 12% are being developed for breast cancer, while ~10% target non-Hodgkin’s lymphoma. Candidates targeting AML and multiple myeloma each represent 7% of the clinical pipeline.
With four approved drugs and nearly 13 in late stages of clinical development,1 the ADC therapeutics market is anticipated to grow at a CAGR of 15% between 2018 and 2021 and 19.4% between 2017 and 2030.2,3
Need for Integrated CMOs in the ADC Space
ADCs present technical challenges as they move from discovery through development and into commercialization, including conjugation chemistry, limited linkers and cytotoxic agents and changes in the biological activity of cytotoxic drugs after conjugation. ADC manufacturing requires a cGMP facility designed with the proper engineering controls to provide product and personnel protection from highly potent compounds. This includes isolators capable of operating at very low occupational exposure levels (OELs). For ADC fill/finish, a fill line with lyophilization capability enclosed in a separate isolator may be an additional requirement. Containment at this level is also required to maintain an aseptic biological manufacturing environment to avoid contamination — a challenge given the potent toxins currently under development.
An ADC manufacturing and fill/finish facility is a substantial investment. Additionally, the supply chain for manufacturing ADCs is complex, including linker/ toxin manufacture, antibody manufacture, conjugation/QC/stability testing and fill/finish. The more operations a CMO can combine as an integrated service, the better for the client, as they provide some clear advantages: (1) technical expertise in conjugation with robust platforms and processes; (2) reduction in time to market by integrating multiple steps, including conjugation, scale-up, commercial manufacturing and fill/finish; (3) reduced sponsor effort associated with management of inventory and logistics by the CMO; (4) flexibility, with changes made during the process coordinated by adept program managers; and (5) lower risk associated with transfers if the different units are co-located. As a result, most pharmaceutical companies continue to outsource manufacturing of their ADCs, with approximately 70% of all ADC manufacturing activities conducted by CMOs.4
The Piramal Advantage
Piramal Pharma Solutions is a global leader in providing integrated ADC manufacturing solutions from development through clinical and commercial GMP batch manufacturing and fill/finish. Our facility in Grangemouth, UK is dedicated to process and analytical development, scale-up and manufacturing of bio-conjugates and is forward integrated with our Lexington, Kentucky facility for fill/finish activities. Our Riverview, Michigan facility provides API for cytotoxic payloads and linkers. We are pioneers in the field of GMP manufacturing of ADCs and have partnered with leading ADC technology companies for 15 years. Our experience is reflected in our record of 880 ADC (lab scale and above) and 440 GMP batches manufactured, 118 development programs completed, 180 different conjugates using over 110 antibodies, 55 different toxin/ toxin-linker systems and six integrated ADC programs across Piramal sites.
Better ADCs for the Future
Wisely chosen target antigens, novel linker technologies and the mode of drug action continue to be investigated to fully optimize ADC-based targeted therapy, not only in oncology but also in other therapy areas, such as infectious, autoimmune and cardiovascular diseases, as pharma companies seek to find wider uses for ADCs.
References
- Sharma, Vivek. “CPhI Annual Report 2018: ADCs Growth Driven by Lack of In-House Facilities, Oncology and Integrated CDMOs.” Pharmaceutical Outsourcing. 10 Oct. 2018. Web.
- “ADC Market to Reach US$ 3 Billion by 2018.” ADC Review.14 Nov. 2017. Web.
- Antibody Drug Conjugates Market (4th Edition) 2017–2030. Rep. MarketsandMarkets. Oct. 2017. Web.
- “Antibody–Drug Conjugates: Manufacturing Challenges and Trends.” ADC Review. 21 Mar. 2017. Web.