Smart bomb ADCs home in on the orphan drug industry

In Clinical Development by Tim Peplow

antibody-drug conjugates orphan drug (sonofgroucho

Antibody-drug conjugates (ADCs) are a tremendously exciting emergent class of targeted cancer therapies, and their presence in the orphan drug industry is becoming ever more noticeable. A monoclonal antibody linked to a biologically active cytotoxic gives ADCs their unique ability to be both specific yet highly potent, as like tiny guided missiles they home in on their target cancer cells to deliver their cytotoxic payload while leaving the healthy cells alone.

ADCs – akin to ‘smartbombs’ – are now cropping up in the orphan drug industry. Indeed, one of the very few ADCs to have received approval is Seattle Genetics’ orphan drug Adcetris (brentuximab vedotin), which gained FDA approval in 2011 to treat two rare forms of lymphoma – Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL).

And there are other ADCs with orphan drug designation also working their way through trials. Immunogen’s lorvotuzumab mertansine (IMGN-901) was granted orphan drug designation by the FDA for the treatment of small-cell lung cancer in 2010, while Bayer’s investigational ADC BAY-94-9343 was granted orphan drug designation by the FDA for the treatment of mesothelioma. Pfizer’s inotuzumab ozogamicin has European orphan drug status for the treatment of acute lymphoblastic leukaemia (ALL), and is currently being evaluated in the phase 3 INO-VATE ALL Study.

However, a second phase 3 trial of inotuzumab ozogamicin was discontinued in May, after the ADC failed to improve overall survival in patients suffering from non-Hodgkin lymphoma. And the first ADC to have ever been approved, Wyeth’s Mylotarg (gemtuzumab ozogamicin), was withdrawn from the market following its groundbreaking debut in 2000. The orphan drug, approved for the treatment of acute myeloid leukaemia, was questioned for its safety and efficacy – and eventually removed from the US market in 2010. This might not be the end of the road for Mylotarg, though, for in late 2011 it was reported that the ADC was shown to help a different group of patients.

ADCs are certain to be a fascinating class of drug to watch, especially as linking technologies improve and off-target effects are reduced. Whether these drugs are treating orphan indications or more common cancers, they have the potential to reduce treatment side effects and revolutionise cancer therapy as we know it.

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Download the brochure for the World Orphan Drug Congress Europe 2013, 14-15 November 2013, Geneva.