Author: Jean-Claude Muller, 穆卓Executive Editor at BtoBioInnovation  jcm9144@gmail.com

SPECIAL REPORT #4

Immuno-Oncology in Adjuvant/Neoadjuvant Settings

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According to a Crédit Suisse analysis, the adjuvant immuno-oncology (I-O) market could reach $29 billion in peak sales.

The study considers the various I-O therapies intended to reduce the risk of relapse in patients and analyses eight cancer types: neoadjuvant lung cancer, oesophageal, gastric and liver cancer, muscle-invasive bladder, renal cell carcinoma (RCC), head and neck cancers as well as breast cancers.  Most breast cancer patients are diagnosed early, which means more eligible patients for neoadjuvant and adjuvant treatment, in sharp contrast with lung cancer patients.

The Crédit Suisse team lead by Vamil Divan, M.D., predicts than Bristol-Myers Squibb’s PD-1 inhibitor Opdivo could become the front runner in the adjuvant I-O market with peak sales reaching $9.6 billion, followed by Roche’s PD-L1 inhibitor, Tecentriq with a potential sales of $7.0 billion, Merck’s PD-1 inhibitor Keytruda with adjuvant sales expected at $6 billion and AstraZeneca’s own PD-L1 inhibitor, Imfinzi with projected sales of $4.1 billion in this setting. These forecasts are surprising given the fact that, except for breast cancer, there are only sporadic positive results for other tumors. “There are more than 30 late stage studies ongoing in various tumor types, but results [in the I-O adjuvant settings] are still missing.  Results must be good enough to create new therapy standards and to balance drug toxicity, quite important in adjuvant treatment” according to Bruno Pagliara, Principal at On-Kòs Pharma.

Divan’s team makes a very interesting analysis in stating that “while there is still much room for I-O growth in the metastatic market for the foreseeable future, in the long run, adjuvant therapy could “cannibalize” the metastatic market. The expanded use of I-O drugs in the adjuvant setting could lead to a substantial reduction in relapse rates thus shrinking the metastatic market over time. For instance, patients who failed in an I-O adjuvant setting may not be eligible for a I-O metastatic treatment.”

Most pharmaceutical companies involved in the development of PD-1, PD-L1 and CTLA-4 products are shifting their current focus from metastatic cancer therapies in the adjuvant, neo-adjuvant, maintenance settings not just because of the fear of “cannibalising” the metastatic market, which is anyway almost fully exploited by the existing and incoming I-O products,  but clearly to expand the current market and gain market share for the new comers to the field. And this goes without mentioning the many I-O combinations with a variety of other accessible treatments under clinical investigation in the metastatic as well as the adjuvant settings.

These considerations and previous ones (see special report #3) contribute to explain the rise in oncology approvals over the years.  They represented 17% of all New Active Substance (NAS) in the 2004-2008 period, 23% in the 2009-2013 period, 25% in the 2014-2018 period and are expected to reach 30% (between 70 and 90 new entities) of all new launches in the 2019-2023 period according to a recent IQVIA report. Many of these new launches will be labelled as precision medicines with the use of biomarkers to segment and best treat appropriate patients. The direct consequence of this strategy will be a substantial increase of price per patient, while the number of patients treated by each selected therapy will be decreasing. These same considerations underly the impressive forecasts made by the Crédit Suisse team for the I-O market in the adjuvant settings.

The median annual cost for these new medicines has risen to tens or hundreds of thousands of dollars or euros and is expected to be more and more challenged by payors. Biopharmaceutical companies will clearly have to propose alternative outcomes-based payment models which support these high prices.

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