NEW MAB APPROVALS
In August 2012, the earlier approval of the drug was expanded by FDA to include diabetic macular edema. This anti-angiogenic
Fab fragment blocks VEGF-A in the eye, aimed at preventing vision loss caused by wet macular degeneration.
As a HER-2/neu receptor antagonist, Perjeta was approved for combined use with trastuzumab and docetaxel for patients suffering
from metastatic breast cancer. When used as a first line treatment, the combination significantly prolonged progression-free
The antibody was approved for the treatment of inhalational anthrax, a form of this infectious disease caused by breathing
in the spores of the bacterium Bacillus anthracis. According to the FDA website, it is the first mAb approved under the Animal Efficacy Rule, which allows findings from well-controlled
animal studies to support FDA approval when it is not possible to conduct trials in humans. Clearly, inhalational anthrax,
being a rare and lethal disease, fits these criteria.
A glyco-engineered, defucosylated, humanized mAb, this innovative product was approved in Japan for the treatment of relapsed
or refractory adult T-cell leukemia/lymphoma. It has also been licensed to Amgen for development as a therapy for asthma.
Adcetris (brentuximab vedotin)
Adcetris was approved by FDA in August 2011 and granted conditional marketing authorization by the European Commission in
October 2012 for relapsed Hodgkin lymphoma and relapsed systemic anaplastic large-cell lymphoma.
BUSINESS AND MARKET
More than 30 approved antibody therapeutics are currently in the worldwide markets, as detailed in Figure 2. The antibodies generated in excess of $45 billion in sales in 2011. More than 40% of this revenue came from anticancer mAbs
such as Rituxan, Erbitux, Herceptin, and Avastin. Remicade and Humira, two of the prominent mAbs for the treatment of inflammatory
diseases such as rheumatoid arthritis and inflammatory bowel conditions, added another $14 billion, or 30% of the total sales.
Figure 2: List of FDA-approved antibody therapeutics.
Humira, the first fully human mAb, developed and marketed by Abbott Laboratories, accounted for $7.9 billion of 2011 sales,
up from $6.5 billion in 2010 and $5.5 billion the year before, a remarkable increase of 44% in just two years. The drug is
poised to become the top-selling therapeutic in the world within the next two years, because it has been approved for use
of as many as seven inflammatory disease indications.
Some analysts predict that with the rate of current revenue growth and with the potential new approvals, the global market
could reach $58 billion by 2016. But as always in the biotech sector, the situation is fluid and extremely difficult to forecast.
Several of the antibodies that were approved during the past decades are still generating multibillion dollars in sales, while
some have been withdrawn from the market due to either severe side effects (Raptiva approved in 2003, withdrawn in 2009)
or lack of sales (Mylotarg approved in 2000, withdrawn in 2010).
Avastin and Lucentis, two anti-angiogenesis mAbs, generated more than $7 billion in sales in 2010. However, Avastin's performance
was mixed. It does not extend lifespan and triggers side effects including high blood pressure and bleeding in metastatic
breast cancer patients. While FDA revoked approval of Avastin for metastatic breast cancer, it still remains approved for
colon, lung, kidney, and brain cancer.
Significant success has been achieved by several ADC companies, including Seattle Genetics and Immunogen, in building partnerships
with pharmaceutical companies. And because of potential benefits expected from ADCs, not only pharmaceutical companies are
generating business deals with new developers of ADCs but even venture investors are putting money into ADC startups. In March
2011, for instance, biotech investor Celtic Therapeutics committed $50 million to back ADC Therapeutics, a next-generation
developer of the products. Additionally, Sutro Biopharma and Celgene struck a deal that could be worth as much as $500 million
plus in milestones and royalties to Sutro.
In some circles, Sutro ADC technology is regarded as "next generation" compared with that of Seattle Genetics and Immunogen.
This assessment is based on its ability to identify optimal sites in antibodies to design a site-specific insertion of non-natural
amino acids for conjugation of linker and payload. Sutro has been on a roll, signing other partnerships with the likes of
pharma giants, such as Pfizer. These as well as investments include investments from Lilly and Amgen venture groups among
The most recent deal completed between Seattle Genetics and Abbott Laboratories could be worth approximately $250 million
when upfront, milestone payments, and royalties are taken into account. The list of Seattle Genetics' collaborators is legion:
Genentech, Bayer, Celldex Therapeutics, Progenics Pharmaceuticals, AstellasPharma, Daiichi Sankyo, Millennium, GlaxoSmithKline,
Genmab, Pfizer, and Abbott Laboratories. Their ADCs or "smart bombs" continue to be one of the hottest new technologies in
the treatment of cancers, given their ability to destroy tumors while minimizing collateral damage to normal cells. The company
has already generated nearly $150 million in sales in the US since Adcetris' approval in 2011.
Immunogen, not to be outdone, has established liaisons with Eli Lilly, Novartis, Amgen, Genentech, Biotest, Bayer, and Sanofi,
among others. Roche/Immunogen's T-DM1 is expected to be approved in February of 2013 as the second ADC in the market. The
drug is a potential blockbuster with projected sales of $5 billion, according to some of the industry analysts.
One of the largest deals involving ADC technology was consummated recently by Italy's Menarini Group. The company has embarked
upon a $1 billion cancer ADC partnership with Oxford BioTherapeutics comprised of fivenew ADC programs.
Although, up till now, ADC programs have been geared to the treatment of various cancers, a recent deal between Merck and
Ambrx focuses on other disease indications, including autoimmune conditions and diabetes. Merck will pay $15 million upfront
with a great deal more (possibly as high as $288 million) in back-end incentives to partner with Ambrx on its ADC technology,
based on proprietary binding methods for linking antibodies to toxins to better control the ratio of toxin molecules to antibodies.