Roche's new sub cutaneous formulation of Herceptin (trastuzumab) to offer increased benefit to early stage breast cancer patients

Herceptin was initially launched in 1999 for the treatment of HER2 positive metastatic breast cancer. Since that time lifecycle management has been stepped up and revenue for this leading monoclonal antibody hit 2.6 billion Swiss francs ($2.5 billion) during H1 2009. LCM activity has included the broadening of breast cancer indications; expansion to evaluate Herceptin as a gastric cancer therapy; and now the reformulation of Herceptin to allow subcutaneous administration.

Having received approval for the treatment of metastatic HER2 positive breast cancer, Roche soon after received expanded EU approval in June 2004 to include use in combination with docetaxel as a first-line therapy in patients who have not yet received chemotherapy. The 2006 approval was granted for the use in early-stage HER2 positive breast cancer following surgery and standard chemotherapy. The FDA granted approval for use in early stage breast cancer in 2008. Recent data reports that at least 80% of women with early stage HER2 positive breast cancer receiving one year of Herceptin were alive free of the disease at 5 years follow-up [press release].

LCM activity has also involved the development of Herceptin for the treatment of stomach cancer, with patients demonstrating improved survival when Herceptin was added to standard chemotherapy in the ToGA trial. This was particularly impressive in HER2 positive gastric cancers. The drug is in pre-registration in Europe for this indication and is expected to be filed soon in the US (for further information see Gastric Cancer - Targeted Therapies Home In On a Neglected Tumor Type)

Improving delivery of oncology therapies has received and will continue to receive considerable attention (see Drug Delivery in Cancer - Technologies markets and companies). In addition to broadening its indications, Roche hopes to draw on optimization through drug delivery development to encourage uptake of a more convenient formulation of Herceptin. This strategy could help to conserve its share of an increasingly competitive market, but may be challenging to implement due to concerns over compliance and financial incentives to prescribe intravenous cancer drugs.

Roche has invested roughly CHF190m ($183m) at two production sites to manufacture devices that will allow patients to self-administer a subcutaneous formulation of Herceptin (trastuzumab; Roche/Genentech/Chugai).

One site will supply the devices for a Phase III study which could support approval of the subcutaneous formulation. In this study, 552 patients with stage I-IIIc breast cancer will receive chemotherapy in combination with either subcutaneous or intravenous Herceptin before surgery, followed by 10 three-weekly infusions of subcutaneous or intravenous Herceptin. The study opened in October 2009 [Press release]

Herceptin's current intravenous formulation requires patients to receive the drug in hospital via a one-hour infusion. The subcutaneous formulation (developed in partnership with Halozyme Therapeutics) would increase convenience, allowing patients to self-administer the drug at home via a five-minute infusion. This is important given that Herceptin is administered for up to a year in early-stage breast cancer. Additionally, this would help to reduce costs associated with patient hospitalization and could improve the drug's side-effect profile by reducing infusion reactions.

Roche will hope that these factors increase brand loyalty and protect Herceptin's market share against potentially fierce competition from GlaxoSmithKline's oral HER-2 inhibitor, Tykerb (lapatinib), which is approved for metastatic breast cancer and is currently in Phase III trials for early-stage HER-2-positive breast cancer. Furthermore, switching patients to a subcutaneous formulation could help insulate against potential competition from biosimilar versions of intravenous Herceptin. As the lucrative monoclonal antibody market approaches maturity, such lifecycle management activities are likely to become increasingly common.

However, Roche could find it challenging to encourage uptake of subcutaneous Herceptin because it will make it more difficult for physicians to ensure patient compliance. Indeed, patient compliance can be a problem for some orally administered anticancer drugs. In the US, financial incentives for oncologists to prescribe intravenous drugs could further restrict uptake of the subcutaneous formulation. The ongoing Phase III study may therefore have to show that the more convenient subcutaneous formulation also has superior efficacy in order to drive appreciable uptake.

For further information on antibody therapeutics in oncology see Monoclonal Antibodies in Cancer Therapy 2009-2024