Appendix 2: Other key drugs in the pipeline
Another product that SGEN has in advanced development with a collaborator is tisotumab vedotin. This an ADC which arose out of a joint ADC research collaboration agreement that SGEN entered into with Genmab AS, a Danish biotechnology company, in September 2010, to develop a drug to target the Tissue Factor, or TF antigen, which is expressed on many solid tumors, including cervical, ovarian, prostate and bladder. By 2018 the drug was being tested in patients with recurrent metastatic cervical cancer in a pivotal phase II trial. It was also being evaluated in a phase II trial with patients with colorectal, non-small cell lung, pancreatic or head and neck cancers. The two companies are sharing the costs for the development and commercialization of tisotumab vedotin and potential future profits equally. SGEN is responsible for its commercialization in the US, Canada and Mexico and Genmab for all other countries.
Another promising targeted therapy that SGEN has in its pipeline is tucatinib. The company paid $614.1 million to acquire the global rights to this drug in March 2018. It did this through an acquisition of Cascadian Therapeutics, a local Seattle biotechnology company. Prior to its acquisition of Cascadian Therapeutics, SGEN had unsuccessfully attempted to buy Immunomedics, a biotechnology company that was developing sacituzumab govitecan (IMMU-132), an ADC candidate that was in late stage development for metastatic triple negative breast cancer. Unlike SGEN's other products, tucatinib is a small molecule drug. First discovered by Array Biopharma and then licensed to Cascadian Therapeutics, tucatinib is designed to target HER2 (human epidermal growth factor receptor 2) ‘tyrosine kinase inhibitor’ (TKI), an enzyme that helps to promote the growth of tumors in HER2 positive cancers. HER2 positive cancers are generally very aggressive and have a poor prognosis for patients. Tucatinib aims to block the TKI wrapped on the inside of the cell. This cannot be done with an antibody because it is too large to penetrate the cell wall (Adams).
SGEN’s decision to purchase tucatinib came after spending many years following the field of HER2 targeted therapy. The company’s executives had studied many different drugs in the area and were particularly impressed with tucatinib. While it is not a new first-in-class molecule, like Adcetris® or enfortumab vedotin, it has several advantages. The first was that, unlike all other similar products on the market, it came in a simple-to use tablet form. Another factor in tucatinib favour was the fact that it did not bind to the EGF receptor, also known as HER1, which some other products do. This was important because any binding to HER1 can cause adverse reactions including skin rashes and diarrhoea, which makes it difficult for women to stay on the therapy for any length of time (Siegall; A/R 2018, p.9).
Tucatinib had already gone through phase I trials by the time it arrived at SGEN and the FDA had granted it orphan drug designation for the treatment of patients with breast cancer whose disease had metastasized to the brain. Such metastases develop in 50 per cent of women with late-stage HER2 positive cancer. One of the major problems for such patients is that many of the breast cancer therapies on the market cannot penetrate the blood-brain barrier (FDA; Array Biopharma). A pivotal phase II trial, called HER2 CLIMB, is also underway for HER2-positive metastatic breast cancer patients who have previously been treated with HER2 targeted drugs. This includes patients with or without brain metastases. Tucatinib is also being evaluated in combination with chemotherapy and other HER2 drugs like Herceptin® and Kadcyla® (SGEN). Data from the pivotal phase II trial is due to be unblinded later this year. The company is also pursuing future trials to test out the drug in other types of HER2 positive cancers, including colorectal and gastric cancer (Siegall; A/R 2018, p.4).
B Adams, 'Seattle Genetics sets $614M buyout of Cascadian and its breast cancer program', Fierce Biotech, 31 Jan 2018, https://www.fiercebiotech.com.Back.
Array Biopharma, https://www.arraybiopharma.com.Back
FDA News, 'FDA grants orphan drug designation to tucatinib for brain metastases', June 13 2017, https://www.healio.com.
Lara V Marks, Lock and Key of Medicine: Monoclonal antibodies and the transformation of medicine (2015).Back
SGEN press release, 'Seattle Genetics to acquire Cascadian Therapeutics, adding late-stage breast cancer program to Its oncology pipeline', 31 Jan 2018, http://investor.seattlegenetics.com.Back
Interview with Clay Siegall by Lara Marks, 12 Feb 2018, notes.Back