Global Insight Perspective | |
Significance | U.K. major GlaxoSmithKline (GSK) is evaluating the effects of Tykerb (lapatinib), Herceptin (trastuzumab) and a combination of both on the tumour of HER2-positive breast cancer patients that have not yet undergone surgery. |
Implications | If Tykerb proves at least non-inferior to Herceptin, then GSK will have a compelling case to push for the drug's approval as a first-line therapy in breast cancer. |
Outlook | The days of Herceptin's market dominance could be numbered, as Tykerb has the added convenience of an oral formulation. GSK's drug is widely expected to reach blockbuster status and fill some of the revenue gap that the company is suffering at the hand of generic competition. Nevertheless, the drug's difficulty to secure reimbursement could hamper its future sales. |
U.K. pharmaceutical company GlaxoSmithKline (GSK) has announced the initiation of the Neo-ALTO Phase III clinical trial that will evaluate the benefits of oncology treatment Tykerb/Tyverb (lapatinib) as a first line treatment in HER-2 positive breast cancer. The studies will be conducted in collaboration with the Breast International Group (BIG) and the Spanish Breast Cancer Cooperative Group (SOLTI). Tykerb is currently approved in the United States and recommended for approval in Europe for use in Her-2 positive advanced or metastatic breast cancer patients who have previously been treated for their conditions with anthracyclines, taxanes, or trastuzumab (Herceptin, Genentech; Roche, U.S./Switzerland; see United Kingdom: 25 April 2008: GSK Makes Progress on European Marketing Authorisation for Breast Cancer Drug Tyverb)
The three-arm, randomised, open-label trial will be conducted in 450 patients in 26 countries. Prior to surgery, HER2 positive breast cancer patients will receive Tykerb, Herceptin or a combination of both over six weeks. Chemotherapy agent paclitaxel (Taxol, Bristol Myers-Squibb, U.S.) will be then added to each arm of the trial for 12 weeks, after which point, patients will undergo surgery. Upon surgery, patients will receive three courses of chemotherapy, which will be followed by 34 weeks of treatment with the initial mono or combination therapy. The primary endpoint of the trial is to assess and compare the rate of complete cancer-cell eradication for all arms of the study at the time of surgery. Secondary endpoints will evaluate Tykerb's safety profile, tumour response rate as well as cancer-free and overall survival rates.
The study is part of GSK's programme to compare the benefits of its drug to that of rival drug and market leader Herceptin. Last year, GSK compared the effects of the two drugs when administered after surgery. Tykerb is the first once-daily oral dual tyrosine kinase inhibitor. Indeed, Tykerb inhibits both the ErbB1 (EGFR) and ErbB2 (HER2/neu) receptors, both involved in cell proliferation, as opposed to Herceptin, which is an injectable HER2 inhibitor. HER2-positive patients are believed to account for around 25% of all breast cancer cases.
Outlook and Implications
GSK has finally initiated the long-awaited head-to-head comparison between its drug and market leader Herceptin. The trials had been on the cards for over a year and if anything come slightly behind schedule. If Tykerb comes out on top in the study, it will support GSK's push to get the drug approved as a first-line treatment and challenge Herceptin's market dominance. The stakes are high for GSK as Herceptin, a drug licensed solely for the treatment of breast cancer, generated first-quarter sales of 1.22 billion Swiss francs (US$1.17 billion) in the first quarter of 2008, while Tykerb brought in £19 million (US$37.13 million) in revenues. The drug has the added convenience of being a once-daily oral treatment compared to Herceptin, which necessitates weekly or three-weekly injections of 30-90 minutes. Although Tykerb has a long way to go before being as profitable as its rival, it is estimated that peak sales could reach an annual US$1.35 billion by 2010 in the breast cancer indication alone. Tykerb also has potential to treat other solid tumour cancers, such as lung cancer, which is expected to boost the drug's peak sales to an annual US$4 billion.
Nevertheless, before Tykerb significantly hurts Herceptin's sales, it will need to successfully pass a few hurdles. Obviously it will need to successfully demonstrate its benefit as a first line treatment and convince regulators that those outweigh the risks associated with the uptake of the medicine (see United Kingdom: 19 March 2008: European Commission Sends GSK's Tyverb Back to CHMP Over Liver Safety Concerns). In addition, to generate significant sales, the drug will need to secure reimbursement status, which so far has not proved straightforward (see Australia: 8 April 2008: Tykerb to Be Added to Australia's PBS). The drug is not reimbursed in the United States, where it has generated over half its first-quarter sales. Failure to secure reimbursement will hamper the drug's sales potential. In the meantime, Roche is aware that it has had a good run with its oncology portfolio whose growth is expected to cool down over the next few year on the back of increased competition. The company has taken steps to offset this slowdown by boosting investment in other therapeutic segments and more specifically in inflammatory diseases (see Switzerland: 15 April 2008: Roche Snaps Up PI3-K Inhibitors Specialist Piramed for US$160 mil.)