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Experts Forecasts CMOs to Benefit from Double Digit Approvals of ADCs

The global ADC therapeutics market is expected to grow to US $ 4bn by 2023, with double digit approvals within 3-years. Novel payloads that target tumor-initiating cells on third generation antibody-drug conjugates or ADCs could come to market in the next couple of years. Driven by a healthy late stage pipeline, experts believe that the market for antibody-drug conjugates will expand at around 19%  compounded annual growth rate (CAGR) between 2017 and 2030.

These growth expectations are based on 17 drugs that are either approved or in late stages of clinical development, catalyzing growth.

Furthermore, the expectation is that outsourcing of ADC manufacturing to Contract Manufacturing and Contract Development and Manufacturers will continue, with increased co-development driven by increased needs from biotechnology companies requiring unique, specialist development expertise and facilities.

But the  most exciting aspect of growth predicted is the expansion of antibody-drug conjugates into therapeutic areas other than oncology. With the development of antibody-drug conjugates in infectious disease, experts believe this to be the next (r)evolution.

Annual Report
These predictions are based on a new analysis published in the 2018 edition of the CPhI Annual Report – the complete findings of which were released earlier this month at CPhI Worldwide in Madrid, Spain, the global pharmaceutical event held October 9 – 11, 2018.

“The last few years have seen a progressive evolution of targets from first to second and third generation antibody-drug conjugates (ADCs), which is now accelerating growth as new compounds are more targeted, more druggable and potentially have a better chance for approval,” said Vivek Sharma, Chief Executive Officer of Piramal Pharma Solutions and co-author of the 2018 CPhI Annual Report.

Better understanding
The understanding of site-specificity and homogeneously conjugated antibody-drug conjugates ADCs has accelerated the U.S. Food and Drug Administration’s (FDA) approval rate and has led to dramatic increase in the number of clinical trials, especially in solid tumors. In total there are now more than 600 clinical trials being conducted worldwide with ADCs. And a  staggering 202 antibody-drug conjugates are entering clinical trials – out of which 116 are actively progressing.

Most encouragingly, there has been an increase of 30% in the last 12 months with 23 new ADCs entering clinical trials.

The report outlines that CMO’s and CDMO’s are particularly well set to capitalise on this growing therapeutic product class, and may even lead to new business models, such as co-development partnerships, particularly among smaller and medium sized biotech companies.

“The global market for ADCs is expected to be driven by the advancement in medical technology, rising incidence of cancer, and an increasing demand for biologic therapies. In the quest for more targeted therapies and potentially more clinically efficacious drugs, biotechnology and pharma companies are increasing their research and product development in biologics” added Sharma.

Technical challenges
Due to technical challenges associated with the manufacturing of antibody-drug conjugates and the substantial investment involved on safety and hazardous material equipment, Vivek estimates that around 70% of ADC manufacturing is outsourced to CMOs. This is expected to rise, particularly for horizontally integrated CDMOs, along with co-development business models, driven by biotechs and smaller companies that need specialist development expertise and facilities.

Other therapeutic areas
In the long term, ADCs are now being utilized in other therapeutic products classes beyond oncology. Specifically, antibody-drug conjugates are projected to provide more targeted therapeutics in infectious diseases (against multi drug resistant bacteria) and chronic conditions such as autoimmune and cardiovascular diseases.[2]

Despite the relatively simple concept, taking antibody-drug conjugates outside the realm of oncology and hematology remains challenging. In contrast, to onclogical indications, non-oncological indications generally require that payloads are delivered to the target cells and modulate biological functions without affecting cell viability. Furthermore, these payloads are non-toxin-based and are largely less potent compared to toxins used in oncology and hematology. As a result, in non-oncological indications, antibody-drug conjugates have a ‘higher standard’ in terms of target selection, antibody carriers, linker chemistry, as well as conjugation approaches to achieve sufficient binding, efficient internalization, and payload release. With a better understanding of antibody-drug conjugates and the applicable chemistries, a number of researchers are currently developing novel, non-oncological ADCs. The expectation is that a larger number of these novel, investigational agents will be included in the ADC-pipeline in the next 3 – 5 years. [2][3]

Small and Large
“The findings in the full CPhI Annual Report further reinforces that there is a clear bridge now forming between small and large molecule industries, with the cross sharing of knowledge in the ADC market leading to less clinical attrition and greater approvals,” said Orhan Caglayan, CPhI Brand Director Europe.

“[This is] clearly extremely promising for CDMOs, and the wider outsourcing industry with over 70% of future manufacturing set to be contracted to specialist providers,” Caglayan concluded.

Note: Download the full findings published in the CPhI Annual Report 2018, which includes 11 in-depth expert contributions as well as the CPhI Manufacturing and Bio leagues tables.

Last Editorial Review: October 23, 2018

Featured Image: IFEMA Feria de Madrid. Courtesy: © 2018 Sunvalley Communication / Evan Wendt. Used with permission.

Copyright © 2018 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.



CPhI Worldwide Attracts a Record of 42,000 Attendees

CPhI Worldwide, organised by UBM EMEA, closed its 27th edition with pre-audit figures indicating a record-breaking attendance of over 42,000 visitors and 2,550+ exhibitors. Held for the first time in Barcelona, Spain (October 4 – 6, 2016), CPhI Worldwide saw participation from 156 countries, an expanded exhibition platform, a revamped industry awards, bespoke content programmes, vast networking opportunities, along with key industry analysis.

The world’s largest Pharma event is a mecca of new trends, industry deals and insights – over 80% of attendance is international, with over 7,000 people travelling from China and India alone. This year, CPhI Worldwide delegates were in a confident mood, with growth looking strong in all segments of the industry. In particular, big Pharma delegates emphasised the need to be first to market in order to maximise profit opportunities – now a key consideration when selecting a CMO. In generics and APIs, Western players reported undertaking high-margin products with complex chemistries, with India and China showing accelerated growth thanks to the continued rise in global use and universal healthcare systems.

“In the last few years… in response to the changes in the pharma industry… we have brought … enriched content …  which was appreciated by more than 42,000 attendees…”

The management of CPhI Worldwide attributes the impressive increase in attendance to its enhanced reputation as a meeting ground for Pharma businesses, inclusive of new market segments – the event had over 120,000 connections within its unique Live Pharma Connect (meet and match) service, with over 12,000 perfect matches being made ahead of the event – and its commitment to delivering high-quality content and knowledge-sharing initiatives, alongside its established trade exhibition.

This year, the event became a five-in-one show, with the first ever Finished Dosage Formulation (FDF) event launched. An impressive 30% of the visitors attended this part of the event alone. FDF was designed to be dedicated to every aspect of the finished dosage supply chain, from Big Pharma and CMO to in/out-licensing and dossier specialists. Advanced formulations, licensing and drug delivery methods across different parts of the supply chain, have seen this part of CPhI grow quickly. Next year, in 2017, it is anticipated that CPhI Worldwide will attract increasing numbers of biopharm players, as companies invest in new technologies and biosimilars – with the US market now opening up and interchangeability gradually being established.

Another major factor in the event’s continued success is its zonal layout – with outsourcing, machinery, and packaging represented by co-located ICSE, P-MEC, and Innopack respectively – all supported by Live Pharma Connect and other networking programmes that facilitated high quality meetings for all attendees. In total, CPhI Worldwide featured 19 different zones covering the entire supply chain, with bio exhibitors becoming increasingly prominent, and a further 22 country pavilions.

The Pharma Forum returned as the dedicated content hub, offering a wealth of information on trends, innovations, developments, and the latest regulatory insights; as well as providing access to the Innovation Galleries, Exhibitor Showcase, Knowledge Hub and Pharma Insights Briefings.

Pre-Connect Congress: ADCs and Personalized Medicine
Complementing this, the iconic Pre-Connect Congress celebrated its 8th edition with sessions on contract services, drug-delivery and design, packaging, FDF, global API production, biosimilars and high potent APIs amongst those featured. The Pre-Connect Congress, held a day before the opening of CPhI Worldwide also included a panel discussion covering antibody-drug conjugates and personalized medicine (biologics and biosimilars).

For many types of cancer, chemotherapy still remains the standard of care. However, chemotherapy is delivered in a way that damages not only cancer cells but also healthy ones. During the panel discussion, attendees heard how antibody-drug conjugates or ADC are changing how cancer cells are targeted and killed. But the process targeted killing via a ‘simple concept’ of delivering a cytotoxic agent linked to an antibody to specifically target a certain tumor marker and kill only cancer cells while sparing healthy cells and reducing side effects, is not as ‘easy’ as it sounds.

LONZA AT CPhI in Barcelona
Photo 1.0: The Lonza Booth at CPhI Worldwide in Barcelona Spain.

“Don’t  believe that you can ‘conjugate’  just any antibody, linker and cytotoxin and expect great results,” noted  Laurent Ducry, Group Leader Bioconjugation R&D at Lonza. “For each drug we have to optimize these three elements.  The right ‘combination’ is not ‘obvious,’ Ducry added.

Antibody-drug conjugates are complex – the antibody, which targets a particular protein, a cytotoxin, which is meant to attack the diseased tissue and a chemical that connects the two, called a linker.

But the complexity reaches beyond the actual ADC. “Some of the target proteins reside on both cancer and healthy cells. As a result, it can be challenging to make these target proteins specific enough to only target cancer cells,” noted Ramesh Dixit, Vice President & Global Head at MedImmune.  “And while most ADCs will get into the targeted tumor cells they will also get in some ‘healthy’ or normal cells. This is not an easy to control,” Dixit further noted.

“Given the complexity of ADCs, we should not be discouraged when the early and preclinical data are not immediately stellar,” David Rabuka, Global Head of R&D Chemical Biology at Catalent Biologics noted. “We should simply follow a stepwise process and strive towards incremental improvement in how we develop novel ADCs,” Rabuka explained.  “… that’s why it is important to choose the right target, linker and cytotoxin,” Mark Wright, Site Lead at Piramal added.

The manufacturing of ADC also requires proper attention.  “One of the key aspects in the manufacturing process is containment,” Richard Denk ar Skan AG, concluded.

Comprehensive market analysis
For more than 4-years, CPhI Worldwide has also delivered comprehensive analysis on a selection of different pharmaceutical markets, ranging from the United States to China. CPhI Worldwide 2016 saw the publication of the 4th CPhI Annual Report: Prospects, Analysis and Trends in Global Pharma, which prophesised the emergence of 3D printed formulations, patented products in China and need to properly define continuous processing methods.

Celebrating the global pharmaceutical industry
Finally, in the celebration of global pharmaceutical industry, the revamped CPhI Pharma Awards took on a new focus, bestowing recognition to companies and innovative products through the 13 awards presented this year, five more than in 2015.

Women in Leadership
Bringing together female executives from across pharma, including Dorene Lynch, Commercial Accounts & Global Marketing Lead at Pfizer  CenterOnem Claire D’Abreu-Hayling, Global Sterile Manager – Global Generics R&D at Teva Pharmaceuticals, Claudia Lin, General manager at AlphaMab and Sarah Hauer, Vice President Business Development, Softgel US & Europe at Catalent Pharma Solutions,  the CPhI Women in Leadership Forum provided an opportunity to exchange knowledge, network, and learn from the experiences of female pharma executives .

Exceeding expectations
“CPhI Worldwide in Barcelona, Spain, has exceeded all expectations, the event was a massive success with the launch of FDF and achieved a record-breaking attendance overall. It’s a real magnet of everything Pharma, and key indicator of the industry’s overall strength,” noted Rutger Oudejans, Brand Director Pharma at UBM EMEA.

“Having over 42,000 attendees is a great achievement and shows the esteemed regard with which it is held globally. In the last few years, we have brought in an increased and enriched content, and more parts of the supply chain in response to the changes in the pharma industry. With the Women’s Leadership Forum, the Pre-Connect and new events we are helping provide a vital platform for global industry to meet, learn and do business. What gives us most pride is that the meetings that take place at Worldwide are integral to the industry’s growth and future innovation. Next year, CPhI Worldwide will visit Europe’s biggest Pharma market once again, and we remain committed to the continuous improvement of our platforms, programmes and initiatives.” Oudejans, added.

Last Editorial Review: October 25, 2016

Featured Image: Guell park in Barcelona, Spain. Courtesy: © Fotolia. Used with permission. Photo 1.o: The Lonza Booth at CPhI Worldwide in Barcelona Spain and Photo 2.0: Celebrating Pharma during the CPhI Pharma Award Ceremony. Courtesy: © Sunvalley Communication. Used with permission.

Copyright © 2016 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.


CPhI Report Sees ADCs as a Key Driver of Tomorrow’s Healthcare

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.

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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