In the first section of the 2013 annual report and industry expert panel, analysts at CPhI Worldwide and CPhI Pharma Evolution describe how they expect that antibody-drug conjugates or ADCs will become a major product group within the oncology market.[1] Their expectation is based on the recent approvals of brentuximab vedotin (Adcetris™, Seattle Genetics/Takeda/Millennium) and ado-trastuzumab emtansine (Kadcyla™, Genentech/Roche). The CPhI report will be published at the annual CPhI exhibition and conference being held from October 22  – 24, 2013 in Frankfurt, Germany. The annual report includes expert in-depth essays. Experts were given carte blanche to evaluate current industry practices and examine the future implications for the industry.

Antibody-drug conjugates have become a hot field in research and development with most pharmaceutical companies either involved or looking to get involved. The rapid growth of ADCs is primarily driven by the flexibility of the various platforms. An interesting observation is that both antibodies and cytotoxins that have previously failed in clinical trials can be given a new lease of life as ADC. Furthermore, ADC have the potential to extend the on-patent life of existing drugs. Kadcyla, for example, extends the potential of trastuzumab (Herceptin®, Genentech/Roche). Finally, the increased complexity of antibody-drug conjugates gives companies a new way in discouraging future development and competition of biosimilars.

While most analysts predict a bright future for ADCs, they also note that the extremely high price of these new therapies – currently available ADCs are priced around $100,000 per patient regimen – is one of main obstacles to the widespread uptake. Notwithstanding the fact that ado-trastuzumab emtansine, for exampleshows benefits over the current best treatment options, achieving high patient uptake at a time of squeezed healthcare budgets will likely be challenging.

Beyond oncology and hematology
But according to Vijay Shah, Executive Director and COO of Piramal Enterprises and one of the invited industry experts discussing his vision in the 2013 annual CPhI report, the outlook for the next few years is particularly optimistic for the antibody-drug conjugates market. Shah envisages increased global investments and even the arrival of a new blockbuster drug to treat a variety of solid tumors. However, beyond the current targeted use of ADCs in targeted cancer treatment, he also forecasts a new class of therapeutic ADC for the treatment of inflammation – demonstrating that antibody-drug conjugates are on the cusp of being the great break-through that many analysts have predicted.

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Unsurprisingly, in the short term the majority of ADCs will be for lymphoma treatment, butInvestigational New Drug (IND) submissions in the US for this class of drug will rise over 50% in the next five years – and ultimately the market will grow to $10 billion during the next 10 years. With such an increase in the prevalence of new targets it’s really only a matter of time before we ADCs provide therapeutic solutions to a range of conditions other than cancer.  Shah expects that this market is likely to grow enormously over the next five, 10 and even 20 years.

“In the past a major failing with antibody-drug conjugates has been that cytotoxic agents were simply not active enough to kill the target cell with such a small amount of payload (0.01%). However, new technologies that improve antibody and antigen conjugation could hold the key to really unlocking their potential. Over the next 10 years we will see ADCs with much higher penetration rates,” Shah explained.

Health based risk assessment
Fujifilm Diosynth Biotechnologies Senior Vice President of R&D and Innovation, Mark Carver, another industry expert, warned however that unless the market moves towards a health based risk assessment approach to single use technologies, innovation could be compromised. Carver expect this to be especially the cases for promising targets like ADCs that are often required to be manufactured in such facilities. According to Carver, “The problem for biologics is that single use facilities are hugely increasing the costs of development and putting at risk promising targets that are deemed unviable before their true potential has been explored. With EMA guidelines likely to exacerbate this trend, many innovative targets are likely to struggle to make it into clinical trials.”

The solution to this problem is health based approaches, so that even when there is only partial data on early phase development work and the likely doses they will be used at to support full PDE and MACO (Maximum allowable carryover) values there is still sufficient information to produce appropriate banding to evaluate risk. The cost reductions and increase in innovation will help accelerate the development of new biologics product classes and it’s now up to the regulators to implement these changes into the way assessments are conducted that maintain safety without compromising innovation.

Similarly, Vision Consulting CEO Dilip Shah has collectively examined the current regulatory environment and concludes that safety and compliance can be both increased by regulators simplifying and unifying their codes and working closer with industry. The problem, however, is that over the last few years and into the foreseeable future there is likely to be an increased number of deliberate infringements (FDA warning letters), particularly as analytical technologies increase. The result of these well publicised large industry infringements is that there is now a very real threat that increasingly restrictive regulations will prevent smaller, more innovative players entering the market. The answer, Dilip Shah believes, will ultimately lie in producing a more transparent process.  Tho be effective, it is crucial that this is a globally unified process where regulators take a more active role in working industry to evaluate procedures in a transparent and consultative manner. However, for this new outcomes-based approach to be successfully implemented, regulators around the globe will need to work together, which, according to Dilip Shah, will not happen for at least another five years.

Agnes Shanley, editor at CPhI Pharma Evolution notes that “This first part of the CPhI Phama Evolution annual report, has been produced with the help of our global expert panel, clearly highlights the growth in biologics and multiuse technologies that will help over the next five years to re-invigorate a period of innovative medicines coming to market- with much excitement and anticipation focussed on ADCs. However, from what we have seen within these first report submissions, it is clear that regulatory reform will be essential to maintaining safety whilst creating an environment that is as flexible as the marketplace to help induce increased innovation.”

For more information
[1] CPhI PhramaEvolution: Annual Industry Report and Industry Expert Panel [Report]

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