Giorgio Bertolini , senior VP of R & D at Olon Group , looks back at how oncology drug technology has developed
Oncology : From cytotoxic compounds to highly selective approaches
Giorgio Bertolini , senior VP of R & D at Olon Group , looks back at how oncology drug technology has developed
Oncology is one of the most important growth markets for the pharmaceuticals industry , partly because of the increasing prevalence of cancer in a world population that is growing and living longer . As some have remarked with grim humour , cancer and cardiovascular diseases are the two most common killers in the developed world “ because we live long enough to get them ”.
However , they are also becoming increasingly common in the parts of the less developed world where lifespans are lengthening the fastest . By some estimates , cancer drugs now account for 30 % of the global pharmaceutical pipeline and 25 % of industry revenues .
Estimates of the size of the global oncology drugs market size by market research companies vary considerably , depending in large part on definitions , but all agree that the market has massive growth potential for the foreseeable future .
Allied Market Research puts it at $ 135.5 billion in 2020 , with a compound annual growth rate ( CAGR ) of 7.5 % to reach $ 274.4 billion by 2030.1 Fortune Business Insights puts it at a basically similar $ 144.3 billion in 2019 , but with a CAGR of 11.6 % taking it to $ 394.4 billion by 2027.2 Precedence Research , whose definition includes diagnostics , basically doubles the market size to $ 286.0 billion in 2021 , with a CAGR of 8.2 %, taking it to $ 581.2 billion in 2030.3
Historical background
One of the first anti-cancer drugs was characterised in the 1950s by Farmitalia Research Laboratories , an Italian research company that identified , from a soil samples , a new strain of Streptomyces peucetius that produced a red pigment . This , after isolation , was demonstrated to be very effective against tumours in mice .
The compound was named Daunorubicin . Clinical trials using this product began in the 1960s , and the drug was successful in treating acute leukaemia and lymphoma . However , its development was stopped in 1967 due to its fatal cardiac toxicity .
By strain mutagenesis , the researchers of Farmitalia were able to isolate a modified strain that was able to produce a new Daunorubicin analogue , later called Doxorubicin . This showed better activity than Daunorubicin against mouse tumours , especially solid tumours . It also showed a higher therapeutic index ( also referred to as therapeutic ratio ), even if the cardiotoxicity remained .
After approval by health authorities , Daunorubicin was commercialised in 1974 as the first approved member of the anthracycline class . To guarantee
New high-containment facility for ADCs under installation at Rodano site its availability , a semi-synthetic process was developed . Commercial production began in the Farmitalia plants with the development of one of the first industrial containment strategies for the handling and production of cytotoxic highly potent APIs HPAPIs .
Olon takes over
With the acquisition of the former Farmitalia sites in 2003 , Olon inherited all the know-how and experience that were developed in these sites over the course of decades . It thus became one of the major players in the manufacture of HPAPIs , integrating every level of containment from initial API development to commercial manufacturing , from a few grams to hundreds of kilos .
Subsequent research has led to many other anthracycline anticancers , or analogues , and there are now over 2,000 known analogues of doxorubicin . This class of drug is still used in the treatment of some specific neoplastic disease .
However , these drugs have many side effects , such as hair loss , bone marrow suppression , vomiting and particularly cardiotoxicity . To reduce these side effects , new , more selective classes were developed , following two alternative strategies :
• Increasing the selectivity of the small molecule itself
• Guiding the highly cytotoxic drugs toward the target cancer cells using an antibody as a seeker , producing a new class of drugs called antibodydrug conjugates ( ADCs ) The first strategy leads to the development of precision medicine , where small molecules were designed
24 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981