2019 has been an outstanding year for biotechnology companies developing anti-cancer drugs, as seen from the large number of approvals given by the Food and Drug Administration (FDA) (approximately 25% of all drug approvals for 2019 were for oncology drugs). These rapid approvals are paving the road for new anti-cancer drug launches, with a total of 27 drugs across 20 indications expected to occur in 2020.
The three most relevant anti-cancer drugs expected to be launched this year are listed below. Two of these three expected releases of approved anti-cancer drugs are for antibody-drug conjugates (ADCs), a class of compounds that seemed to have lost the interest of biotech companies following some prominent clinical trial failures, but have apparently made a strong comeback last year. ADCs are monoclonal antibodies attached by chemical linkers to biologically active compounds, such as chemotherapeutics. By combining the unique targeting properties of monoclonal antibodies with the cancer-killing ability of cytotoxic compounds, ADCs allow sensitive discrimination between diseased and healthy tissue. This type of therapy brings innovations from chemistry and biotechnology together in a new class of highly potent biopharmaceutical compounds.
The first anti-cancer ADC approval of 2019 was given by the FDA in the last month of the year to Padcev®, a first-in-class ADC directed against the cellular adhesion molecule nectin-4 overexpressed in bladder cancer. The accelerated approval was given 3 months ahead of schedule, for the treatment of patients with locally advanced/metastatic bladder cancer who previously received a programmed cell death protein-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy in the neoadjuvant/adjuvant. During the pivotal Phase II trial that was the basis for its approval, enfortumab vedotin-ejfv led to an overall response rate (ORR) of 44%, and a median response duration of 7.6 months. Overall, 2019 was a very good year for Seattle Genetics, whose first approved cancer drug, Adcetris® (brentuximab vedotin), was responsible for 30-42% growth/quarter compared with the same periods in 2018. Adcetris® is also an ADC, which selectively targets tumor cells expressing the CD30 antigen and is used for treatment of relapsed/refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Once Padcev® is released, the cost-per-patient for a full course of treatment is approximated to be $110,000-$120,000, which places the drug’s estimated revenue value at $2.7 billion in 2024.
Enhertu®, another ADC, received accelerated approval (4 months ahead of schedule) only two days after Padcev®, for the treatment of patients with unresectable/metastatic human epidermal growth factor 2 (HER2)-positive breast cancer who received ≥2 prior anti-HER2-based regimens in the metastatic setting. Due to its composition, Enhertu® has exerts two types of anti-cancer activities. The antibody component, trastuzumab, attaches itself to the HER2 receptors on the surface of cancer cells and blocks them from receiving growth signals. The topoisomerase I inhibitor deruxtecan exerts its mechanism of action by interfering with the cell cycle and generating single and double-stranded DNA breaks that harm genome integrity, ultimately leading to cell death.
In a pivotal Phase II trial, this anticancer therapy led to an ORR of 60.3%, and a median response duration >1 year (14.8 months). These are quite remarkable results in a patient population with few remaining treatment options. Enhertu® is planned to be launched in Feb2020 at a cost-per-patient of approximately $13.300/month, which is estimated to lead to $68 million in US sales by the end of 2020 and to an estimated revenue value of $2.4 billion in 2024. The drug is currently under review in Japan.
The last of the three approved anti-cancer drugs expected to be a blockbuster launch in 2020 is Brukinsa®, a Bruton’s tyrosine kinase (BTK) inhibitor that decreases the endurance of malignant B cells by binding to the active site of BTK and thus inhibiting cell proliferation and survival. Brukinsa® was approved by the FDA in November 2019 for the treatment of adult patients with relapsed/refractory mantle cell lymphoma who have received at least one prior therapy. Similar to the previous two drugs, Brukinsa® also received an accelerated approval, the first for a drug of a Chinese biotechnology company to be used in the US population. In the pivotal Phase I/II clinical trial leading to its approval, zanubrutinib led to an 84% response rate (tumor shrinkage), with a median response duration of 19.5 months in a difficult-to-treat patient population. These results compare well with those of Imbruvica (ibrutinib), another BTK inhibitor currently marketed by Johnson&Johnson and AbbVie, and which received an accelerated FDA approval in 2013 for treatment of the same group of patients after showing a response rate of 66%. Of note, in the first nine months of 2019, Johnson&Johnson and AbbVie reached combined sales of $5.9 billion with Imbruvica. Furthermore, the approximative costs of a 30-day supply of Brukinsa® are $12.935, similar to Imbruvica’s current price. Taking this into account, Brukinsa’s® estimated revenue value in 2024 is placed at $2.2 billion.
Based on the estimated global sales for 2024, these drugs are anticipated to break the blockbuster barrier in the upcoming four years and change the current immuno-oncology pharmaceutical landscape. Furthermore, due to their unique modes of action and observed clinical results, these promising compounds seem to successfully address an unmet need in patients with few remaining treatment options.