Last week the FDA approved Roche/Genentech's T-DM1 for recurrent, metastatic HER2-positive breast cancer (BC) patients who have previously received Herceptin and a taxane1. T-DM1 (trastuzumab emtansine) is an antibody-drug conjugate (ADC) made up of the antibody, trastuzumab, and the chemotherapy agent DM1. It functions by combining the cytotoxic effect of chemotherapy with the specificity of antibody mediated targeted therapy, to provide a better efficacy and safety profile. In fact, T-DM1 increased median overall survival by almost 6 months, a significant gain to the current standard of care, in a large head to head clinical trial1. Approval of T-DM1, which will be marketed as Kadcyla, was eagerly awaited by patients and physicians; and we expect rapid uptake of T-DM1.

T-DM1 is the fourth to market for HER2 positive BC, following Herceptin, Tykerb and Perjeta.  The BC market is expected to grow to $10.9B by 2018 (from $8.7B in 2011). Share of HER2 targeting agents is expected to increase to 55%2, even though HER2 positive cancers comprise 20% of all BC. T-DM1, priced at $9800/month, and $94,000 for a typical regimen lasting 9.6 months, is poised to be a blockbuster with peak sales projected in the $2 to $5 billion range3 and to drive the increase in market share of HER2 targeting therapies.

This is good news for Roche: Roche group sales (totaling $48.5B in 2012) are currently driven by cancer therapeutics such as Rituxan, Herceptin, Avastin, which together comprise about 38% of its overall sales4. Future growth will be driven by T-DM1. However, Roche also faces imminent revenue loss owing to a cheaper Herceptin biosimilar expected to hit the market in the coming years. In fact, Roche's Genentech unit, which will be marketing T-DM1, plans to make it available to patients within a matter of weeks, to maximize T-DM1 generated revenues. Besides, T-DM1 itself could cannibalize Herceptin sales in the near future, as late stage clinical trials comparing T-DM1 with Herceptin as first line mBC therapy and as adjuvant therapy for early stage BC are currently underway5. Roche licenses technology for T-DM1 under an agreement with ImmunoGen, Inc., which will receive royalties on sales of up to 3-5%.

Besides bolstering Roche's strong cancer portfolio and bringing hope for thousands of patients with mBC, FDA-approval of T-DM1 has another significant implication: it is an important victory for the concept of ADC, for both Roche and ImmunoGen. Although an area of active research, development of ADCs has been challenging and until now has been met with limited fruition. Only one other ADC, brentuximab vedotin, is currently FDA-approved (for relapsing and refractory Hodgkin's lymphoma and systemic anaplastic large cell lymphoma)6. Another ADC, Mylotarg was withdrawn from the market in 2010 when a post approval clinical trial showed that the drug increased fatality7. T-DM1 is the first FDA-approved ADC for treating HER2-positive mBC, making it suitable for a large patient base for the first time. Its approval validates ImmunoGen's ADC technology, on which many of its remaining assets are based, and bodes hope for the rest of its pipeline. Roche currently has 25 ADCs in its pipeline targeting different types of cancer, including eight in clinical trials, and approval of T-DM1 is no ordinary encouragement for these ADCs in development. However, post launch safety studies for T-DM1, required by the FDA, will be closely followed.

Mandrita Bagchi is an Associate Consultant with the DRG Consulting group.
 

Sources:
1Roche Media Release Feb. 22, 2013 - FDA approves Roche's Kadcyla (trastuzumab emtansine), the first antibody-drug conjugate for treating HER2-positive metastatic breast cancer (New personalised medicine helped people in Phase III study live longer, compared to standard treatment)
2Decision Resources Pharmacor Report - Breast Cancer;  Jan. 2013
3FDA Approves Breast-Cancer Drug ? Wall Street Journal and Fierce Biotech Report : http://online.wsj.com/article/SB10001424127887324503204578320150153795188.html and http://www.fiercebiotech.com/story/rochegenentechs-breakthrough-t-dm1-wins-blockbuster-ok-breast-cancer/2013-02-22?utm_medium=nl&utm_source=internal
4Roche Annual Report 2012 http://www.roche.com/about_roche/at_a_glance/key_facts_and_figures.htm?tab=2)
5NCT01120184 (MARIANNE) and NCT01745965- http://www.clinicaltrials.gov
6http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails
7Mylotarg Market Withdrawal - http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm216458.htm

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