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Market Growth, Demand, Trends and Share of Antibody-drug Conjugates (2017 – 2025)

A report published by Persistence Market Research (PMR), a U.S.-based full-service market intelligence firm specializing in syndicated research, shows that the global market for antibody-drug conjugates or ADC is expected to be driven by the advancement in medical technology.[1]

According to the report, the key drivers of the market are the increasing cases prevalence of cancer, growing ageing population and increase in obese population.

Furthermore, the increasing research activities on antibody therapies, pre-clinical research, more research on advanced drug discoveries and increasing research on oncology diseases and the growing collaboration between research institutes, biotechnology and biopharmaceuticals companies is also acting as a fuel to the market and is expected to drive the market of antibody-drug conjugates within the forecast period of 2016-2024 discussed in the report.[1]

However, the high cost of the procedures and the lack of fund can be the restraint for the growth of this market.

Three parts- an antibody specific to target
Antibody-drug conjugates or ADCs are composed of three parts- an antibody specific to the target associated antigen, antigen that has restricted expression on normal cell, a cytotoxic agent designed to kill target cancer cells and a chemical linker to attach cytotoxic agent to the antibody.

The report’s authors conform that there are 243 antibody-drug conjugates in clinical pipeline for the treatment of cancer. Majority of these agents are investigational drugs in pre-clinical development followed by a considerable agents in phase I – III clinical trials.

These unique, targeted, drugs have therapeutic potential and contains both technological and developmental challenges. ADCs are considered to be the new age of therapeutic agent. They combine the targeting ability of monoclonal antibody and the target specific cell killing ability of cytotoxic drugs.

Success as a result of Technological advances
The success of this technology has become possible only with the increasing technological advancements. Antibody drug conjugates is the new class of therapeutic agent that is gaining attention from both large and small pharmaceutical companies.

The potency of the cytotoxic drug in antibody drug conjugate is 100-1000 fold more than the potency of cytotoxic drug when it acts alone.

Though this technology provides presence to maximum large pharmaceuticals companies, the capabilities for the development of ADC still lies with very few companies. There are many products under pipeline. Most development today has been carried out under license agreements.

The major advantage of using antibody-drug conjugates is that it brings together the best characteristics of both antibodies and the cytotoxic potential of chemotherapy. This offers significant opportunity for the market in terms of targeted accumulation of drug in the tumor cell or tissue. Apart from this there are several other benefits of antibody drug conjugates which are driving the market and will be accelerating its share in the upcoming future. [2]

Approved
There are only three antibody drug conjugates that have received approval from the U.S. Food and Drug Administration (FDA).

The first antibody-drug conjugate, gemtuzumab ozogamicin (marketed by Pfizer/Wyeth as Mylotarg®; previously known as CMA-676) was granted accelerated approval by the FDA based on promising phase II data in relapsed older adults with acute myeloid leukemia (AML).

The drug held promise as a new agent that also could be efficacious in newly diagnosed AML with acceptable toxicity. Several phase III studies were designed to test gemtuzumab ozogamicin in this setting.

The results of a randomized study by the Southwest Oncology Group led in 2010 to the voluntary withdrawal by the manufacturer of this agent when improved efficacy could not be demonstrated and toxicity appeared to be excessive.

Since the withdrawal, 4 randomized studies have been completed that, in aggregate, strongly support the efficacy of this agent in newly diagnosed AML with acceptable toxicity. Based on the results of these studies, it seems that there is a very plausible explanation for this discrepancy. When confirmed, researchers believe that there is a compelling case for re-approval of gemtuzumab ozogamicin in the treatment of patients with AML.[3]

In late January 2017 Pfizer’s Biologics License Application (BLA) for gemtuzumab ozogamicin was accepted for filing by the FDA. in addition, a Marketing Authorization Application (MAA) for review by the European Medicines Agency (EMA) was validated in December 2016.[4]

Increased investments
The number of companies developing methods for antibody drug conjugates technology has not significantly changed in recent years. The increasing investment by the pharmaceutical and Biotechnology companies is expected to drive the market. Based on the product type the market is segmented to brentuximab vedotin (Adcertis®; Seattle Genetics/Takeda) and ado-trastuzumab emtansine (Kadcyla®; Genentech/Roche).

Brentuximab vedotin
Brentuximab vedotin is indicated for patients suffering with classical Hodgkin lymphoma (HL) after failure from at least two multi-agent chemotherapy regimen in patient who are not auto-HSCT candidates or patient with failure of autologous hematopoietic stem cell transplantation, HL patients at high risk of relapse or progression as post- auto- HSCT consolidation and lymphoma patient after failure of at least one prior multi-agent chemotherapy.

Drugs was granted accelerated approval for Biologics License Application (BLA) by the U.S. Food and Drug Administration (FDA) for its usage in relapsed and refractory Hodgkin’s lymphoma and large cell lymphoma.

Ado-trastuzumab emtansine
Ado-trastuzumab emtansine it is the first HER2-targeted treatment of its own kind for metastatic breast cancer. It contains two cancer- fighting drugs in one. It contains monoclonal antibody trastuzumab, which the same monoclonal antibody in Herceptin® (Genentech/Roche) and a chemotherapy called DM1.

Ado-trastuzumab emtansine is indicated as a single agent for treatment of HER2-positive, metastatic breast cancer in patients who previously received trastuzumab and a taxane, separately or in combination.

Unprecedented tumor response and clinical benefit
A different report, Global Cancer Antibody Drug Conjugates Market & Clinical Pipeline Insight 2022, published earlier this year by Kuick Research, shows that for a number of cancers where validated predictive biomarkers are available, administration of targeted therapies such as antibody-drug conjugates, PD-1s and others, have been associated with unprecedented tumor response and clinical benefit. [2]

The authors of the report confirm that efforts to design tolerable combination therapies involving antibody-drug conjugate, cancer vaccine, immune checkpoint and kinase inhibition are rational means of maximizing clinical benefit in the targeted delivery of anticancer therapies. [2]

ADC-market
By end user, the global antibody-drug conjugates market has been segmented into Hospitals, Specialized Cancer Centers, Academic Research Institutes, Biotechnology Companies, Biopharmaceutical Companies and others.

By regional presence, antibody drug conjugates market is segmented into five key regions viz. North America, Latin America, Europe, Asia-Pacific, and the Middle East & Africa. North America will continue to dominate the antibody drug conjugates market as it has high experienced professionals and better healthcare facilities. Europe is expected to hold second largest market share in global antibody drug conjugates market.

The growing government initiatives and increasing number of biotechnology and biopharmaceutical companies in the Asia-Pacific region is also driving the market of Antibody-drug Conjugates.

According to Visiongain Ltd, the global next-generation antibody therapies market, which includes antibody-drug conjugates, is expected to grow at a CAGR of 35.9% in the first half of the forecast period. The market is expected to grow at a CAGR of 22.4% from 2016-2027.

The market is estimated at $3.1bn in 2016 and $14.1bn in 2021.


Last editorial review: June 30, 2017

Featured Image: Display of Stock market quotes. Courtesy: © 2017. Fotolia. Used with permission. Photo 1.0: Packaging/vial gemtuzumab ozogamicin (Mylotarg®; Pfizer/Wyeth). Courtesy: © 2017. Pfizer. Used with permission. Photo 2.0: Packaging/vial  brentuximab vedotin (Adcertis®; Seattle Genetics/Takeda). Courtesy: © 2017. Seattle Genetics. Used with permission. Photo 3.0: ado-trastuzumab emtansine (Kadcyla®; Genentech/Roche). Courtesy: © 2017. Genentech/Roche. Used with permission.

Copyright © 2017 InPress Media Group, LLC. 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.

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Andrew Huang: “ADC’s Are Among the most Powerful Options to Increase Drugability of a mAb”

With a population of 1.4 billion [*] and a rapidly expanding economy, China has become a manufacturing powerhouse. In addition, China is pursuing a goal of becoming a major hub for international bio-pharmaceutical product research, development and manufacturing. In realizing the first steps in this ambitious goal, China has, over the past decade, become a major destination for the global pharmaceutical industry to conduct R&D activities. This growth has drastically changed the pharmaceutical landscape, challenging Chinese companies in raising the quality of their products, while, at the same time, challenging them in expanding their development and manufacturing capacity to serve both global and national markets. [1]

Partly the results of China’s population growth and increasing domestic medical needs, the country has, according to a recent report published by UBM’s CPhI China, become the world’s biggest producer and exporter of active pharmaceutical ingredients or APIs.  Today, the country is responsible for nearly 40% of global API production. But the Chinese pharmaceutical market has still huge opportunities for growth. 

With government’s increasing investment in healthcare and R&D, China offers unique opportunities for innovative products and technologies, and collaboration between global and domestic pharmaceutical companies.

According to the China Food and Drug Administration (CFDA), the government’s significant investment in healthcare led to an increased – and more innovative – R&D pipeline and a growing importance of China as center of bio-pharmaceutical development and manufacturing.  The government’s investment has also cultivated companies with capabilities that are comparable – and competitive – with North American and European R&D, putting high-cost, global-centric R&D models at a real disadvantage.

Eliminating Concern
The growth of China’s bio-pharmaceutical industry is also the result of effectively securing Intellectual Property (IP) rights.  IP rights are among the most valuable resources for pharmaceutical and biotech companies, and their  protection often dictates the future success of the companies involved. While poor IP protection and enforcement have often been cited as limiting factors in the growth of pharmaceutical companies’ drive to carry out R&D in China, recently revised patent laws have increased overall global trust and are expected to effectively deter copycat drug makers.  And while, according to the US-China Business Council, some concern remains, China’s IP laws and regulations increasingly reflect international standards, allowing Chinese authorities to better protect and enforce IP rights.[2]

According to a study about the business of life sciences, pharmaceuticals and healthcare sector in China, published by Deloitte China Life Sciences and Health Care in Shanghai, the increased IP protection and enforcement has resulted in a growing number of global pharmaceutical companies being increasingly attracted to the idea of having a R&D center in China or, alternatively, partnering with Chinese partners.[3]

Furthermore, a general low cost base, a large pool of highly qualified research subjects, increasing scientific capabilities, the local industry’s knowledge, a general lack of regulatory and cultural impediments often found in other countries and insight into the country’s growing drug markets have made China an attractive country for R&D.

Ambitious Plans
In China, regulatory approval for pharmaceutical agents is based on clinical trials that have been carried out in the country. This requirement has also contributed to the global pharmaceutical industry’s interest in conducting clinical trials in China – and, as a result, work with a Chinese contract research organization (CRO) and contract (development) and manufacturing organizations (C(D)MO).

The regulatory environment has, no doubt, boosted China’s ambitions plans to be a primary market for CROs and CDMOs. Most of the top 20 multinational pharmaceutical companies have been expanding their footprint in China by setting up R&D facilities through various enterprise structures. Large companies including Bristol-Myers Squibb (BMS), Pfizer, Roche, GlaxoSmithKline (GSK), Johnson & Johnson and Novo Nordisk continue to develop partnerships with Chinese companies.

This approach mitigates traditional development risks but also leverageg local efficiencies, allowing companies to add operational value due to familiarity with the market and regulatory requirements, leading to shortened approval times and reduced development costs. In turn, Chinese CROs are recruiting expert Chinese nationals with research experienced nurtured at top Western pharmaceuticals companies to staff domestic CROs.

Moreover, global pharmaceutical companies are starting to conduct R&D activity specifically related to Asian markets. The specificity is linked to the environmental, cultural and genetic factors, liver disease, certain cancers, and some communicable diseases that are more common in Asian countries, such as China and Thailand than in other countries around the world.

Expanding facilities
Among the growing CRO/CDMOs in China is MabPlex International. Based in Yantai, a port city in Shandong province, China, and founded in 2013, the company specializes in the development and GMP manufacturing of recombinant proteins, antibody therapeutics and antibody-drug conjugates for its global customers. To accommodate growing demand, MabPlex, in October 2016,  broke ground on the expansion of its bio-manufacturing facilities.

The construction of company’s new 428,000 sq. ft. facility is expected to be completed by August of 2017, with utility and HVAC validation finished by December 2017.  The fill/finish facility will be completely validated by March of 2018.

Earlier this year we interviewed Andrew C. Huang, MabPlex’ Senior Vice President of R&D. Huang has developed a robust and proprietary technology platform for the manufacturing antibody-drug conjugates based on covalent thiol conjugation Technology. The resulting Hertuzumab Vedotin, the first ADC being developed in China, has entered Phase I and Phase II clinical trials.

Prior to joining MabPlex International, Huang served for more than 17 years as a biomedical researcher at the University of California, Los Angeles (UCLA), a public research university in the Westwood district of Los Angeles, engaging in molecular medicine, including brain aging, diabetes, stem cells and protein folding research. He has published near 100 research articles, journal reviews and book chapters. During our interview we asked him about his company, the role his company plays in global bio-pharmaceutical development and manufacturing, the current expansion, the potential for antibody-drug conjugates and the regulatory env

Question/Peter Hofland: What excites you the most about the potential of ADCs?

Answer/Andrew Huang: Antibody drug conjugates are one form of combinatorial therapy that uses tumor-targeting antibodies and high-potency chemical drugs. Most antibodies alone have limited efficacy against malignant cancers. The efficacy of an antibody often increases synergistically when conjugated to a high-potency chemical drug. In addition to the enhancement efficacy, the ADC platform can rescue some  cytotoxic drugs, which are too toxic or have poor bioavailability on their own.

PH: What are your company’s major accomplishments over the past 12 months?

AH: We have completed several ADC projects, including providing ADCs for phase II clinical trials and one successful IND with better than expected results.

PH: … and what are your expectations for the next 12 months?

AH: Our ADC projects from US-based clients gradually increased over the last 12 months. And we expect that this will continue in the foreseeable future. That’s why we are expanding our ADC manufacturing capacity to accommodate [the doubling of the number of ADC projects].

PH: As a CDMO, what are the top three things that sets your company’s next-generation ADC platform apart?

AH: I think that there are three things that set us apart. The first thing includes our cysteine conjugate platform and our product quality in terms of conjugation efficiency and fraction of DAR4. The second differentiator is our proprietary thiol covalent conjugation technology and finally, our faster speed and efficiency of completing client’s task as compared to (other) leaders in the field.

Pharma/Industry Questions
PH: MabPlex International is based in China. How big is the role of Chinese CDMOs in the world?

AH: The Chinese are gradually increasing their role as a worldwide CDMO family. However, right now, Chinese CDMO companies are limited in capacity because most Chinese companies focus mainly on Chinese business and they are not familiar with rules and business outside China. But that’s changing. Currently, more and more Chinese companies are starting (representative) offices in the United States and Europe to explore opportunities.

PH: How is the approach of Chinese companies different (or similar) to the approach of CDMOs in North America and Europe?

AH: Most CDMO companies in China are led by US/Europe “returnees” so most approaches are likely to be the same or (very) similar. The significant difference will be to fit Chinese “culture” and how to bridge the Eastern culture to Western one.

Regulatory landscape
PH: The unique properties of ADCs create technical challenges that require careful CMC considerations. Based on your experience in the development of ADCs what are some of the current regulatory challenges (with special focus on CMC)?

AH: A few years ago, during the Cambridge Healthtech Institute’s inaugural CMC Strategies for Antibody-Drug Conjugates meeting in Boston, Massachusetts, someone answered the same question by saying that antibody-drug conjugates are conceptually, very simple, but in practice, extremely complicated.  And I must agree with that. In it’s ‘simple’ complexity ADCs combine a monoclonal antibody, a chemical linker and a cytotoxic drug. Simply stated, as a result of the complex nature of an ADC, we need triple the amount of control and characterization to achieve the right formulation, stability and consistency for effective scale up and manufacturing if we want to meet the regulatory requirements.

And with the increased number of ADCs coming down the pipeline, it becomes imperative for pharmaceutical and biotechnology companies to consider the manufacturability of the ADCs. This means that they have to incorporate process design and CMC strategies early on in the development stage of an ADC.

Looking at our experience, some of the technical challenges require careful CMC considerations include homogeneous drug distribution, the highest possible fraction of DAR4 and the lowest possible fraction of DAR6 or higher with cysteine conjugation.

PH: Overall…What do you see is the biggest challenge in the development of ADCs?

AH: That’s the degree of homogeneous drug distribution.

But manufacturing ADCs not only involves technical challenges but also challenges in the areas of externalization of manufacturing, supply chain management and new technology considerations. That’s why regulators, looking at the highly toxic nature of ADC payloads, as well as the monoclonal antibody and linker chemistry thta make up an ADC, are concerned about the safety, potency and stability of the product and the workers involved in manufacturing it.

Regulatory implications
PH: How is the regulatory landscape in China different than the European of North American regulatory landscape?

AH: A few years ago, regulations in China for CDMOs were significantly different when compared to Western regulations. At that time the drug license and MFG (Drug Manufacturing) license had to be the same. This greatly limited Chinese CDMO development. However, after November 2015, China adopted a new policy for Marketing Authorization Holders (MAH). This new policy is similar to policies in the United States and Europe: the licenses for marketing authorization and manufacturing are separate.

PH: How has the creation of the China Food and Drug Administration (CFDA) and a restructuring of its regulatory system benefited Chinese CDMOs and in particular, your company?

AH: As mentioned, starting in November 2015, China enforced a new policy for Marketing Authorization Holders similar to policies in the United States and Europe. Prior to 2015, all bio-pharmaceutical companies were required by the China Food and Drug Administration (SFDA) to complete the biologic drug CMC and formulation-fill-finish by themselves. Only a chemical drug could be outsourced or contracted out to CRO/CDMOs. Now, biologics, like any chemical drugs, can be outsourced to CRO-CDMO, like MabPlex.  This includes  R&D and CMC, formulation, fill-finish and even IND submissions.

PH: One often heard concern from companies in North America and Europe is that despite vast improvements, concerns still persist about enforcement of intellectual property (IP) and patent laws in China. How does that impact CDMO business in China?

AH: These concerns have a deep impact on CDMO’s in China. We believe the only thing we can do is to continuously improve our IP enforcement, which is already at Western standards. In addition to our secure enforcement of IP protection, MabPlex has a morning meeting each day to emphasize to all our employees three things: IP, GMP and Safety!

PH: … and how does this, specifically, impact your business?

AH: Companies, especially North American and European companies, are still a little hesitant in dealing with new companies like us. However, we see more and more companies from the United States starting ADC business with us. We are confident that we will prove to our US and European colleagues that we are a trustful and reliable partner.

PH: Your company is experienced in ADC development and manufacturing. Are you planning to expand with additional development and manufacturing facilities in North America and Europe?

AH: We already established a branch (MabPlex Inc. USA) in USA last year. But our US branch will not include manufacturing.


[*] 2017

Last Editorial Review: May 24, 2017

Photo 1.0: Andrew C. Huang, MabPlex International’s Senior Vice President of R&D. Courtesy: © 2017 MabPlex  Featured Image: MabPlex headquarters, Yantai, Shandong, China. Courtesy: © 2017 MabPlex. Used with permission.

Copyright © 2017 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.

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