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Medicine

Delivering clinical and commercial impact through novel monoclonal antibody cancer treatments

University of Southampton research has underpinned the clinical development of anti-cancer monoclonal antibodies. The most advanced are ofatumumab (trade name Arzerra) and obinutuzumab (trade name Gazyva), which are used to treat B cell diseases such as chronic lymphocytic leukaemia and follicular lymphoma.

Context

Genetic maps

Biologics are large biomolecular drugs, now commonly used in the treatment of human disease including cancer and autoimmune disorders. They comprise half of the top ten blockbuster pharmaceuticals and gross around $30 billion per year worldwide.

Eighty per cent of these biologics are ‘monoclonal antibodies’ (mAb). Researchers at Southampton have played a leading role in bringing two types of anti-CD20 mAb from the lab to the clinic to treat B cell disorders such as leukaemia and lymphoma. B cells are a type of white blood cell for which CD20 is a crucial marker in the diagnosis of these cancers.

Research challenge

In 2002, Professors Martin Glennie and Mark Cragg discovered two distinct types of CD20 antibodies. These shaped the pharmaceutical industry’s development of a new generation of drugs to target B cells for treating blood cancers.

In 2004, Professor Glennie joined Danish biotech firm Genmab for a six-month sabbatical, during which he led a small research team that developed a next generation CD20 mAb capable of replacing the first-in-class ‘gold standard’ therapeutic antibody rituximab.

Professor Glennie’s team at the University went on to create and patent ofatumumab, which, unlike rituximab, is a fully human antibody, and is more potent at engaging the complement system.

Professors Cragg and Glennie, alongside Professor Stephen Beers, continued to explore the relative potency of Type I and II mAbs leading to the development of a third generation anti-CD20 mAb, Roche’s type II drug, obinutuzumab.

Clinical and commercial impact of ofatumumab (Arzerra)

Ofatumumab was approved by the FDA in 2009 and the EU in 2011 for the most prevalent form of leukaemia, chronic lymphocytic leukaemia (CLL), after Southampton researchers proved it was able to kill target cells resistant to similar drugs.

In 2016, it was approved by the FDA as a treatment for recurrent or progressive CLL and for relapsed CLL in combination with Fludarabine and Cyclophosphamide.

Its ability to delete B cells has been assessed in autoimmune conditions such as rheumatoid arthritis, which affects more than 400 million patients worldwide, and multiple sclerosis, which affects more than 2 million.

Ofatumumab’s commercial impact since 2013 has been highly significant, achieving sales revenues of more than $200 million, translating to £40 million in royalties for Genmab. GSK’s rights to its use in cancer were acquired by Novartis in August 2015 in a deal worth up to $1 billion.

Clinical and commercial impact of obinutuzumab (Gazyva)

Globally, leukaemia accounts for some 300,000 new cases each year with 222,000 deaths
Monoclonal Antibody cancer treatmen

Obinutuzumab was FDA-approved for CLL in November 2013 and follicular lymphoma in November 2017, changing frontline clinical treatment of these diseases. It has also been assessed in clinical trials from post-transplant lymphoproliferative disorder and renal disease, to lupus where the FDA granted Breakthrough Therapy Designation for adults with lupus nephritis.

Sales of Gazyva have grown considerably year-on-year since its FDA approval in November 2013, reaching over £500 million in 2020.

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