Renal cell cancer (RCC) disease forecast and market analysis to 2038
Author: Tom Tyler
Publisher: Datamonitor Healthcare
Renal cell carcinoma (RCC) is a tumor that originates in the renal cortex, the outer part of the kidney between the renal capsule and the renal medulla. Around 85% of all malignant kidney tumors are RCC, with other types including transitional cell carcinoma of the renal pelvis and Wilms tumor (nephroblastoma). The incidence of RCC is higher in those over the age of 60 years, suggesting that the aging population may play a significant role in current and future disease burden. Overall, RCC incidence rates have been steadily increasing in both men and women in the US, Japan, and five major EU markets since the 1970s.
- Datamonitor Healthcare estimates that in 2018, there were 338,000 incident cases of renal cell carcinoma (RCC) worldwide in those aged 40 years and older, and forecasts that number to increase to 384,000 cases by 2027.
- The majority (75%) of RCC cases have a clear cell histology (ccRCC), to which most first-line treatment regimens are specialized. The next most common histology is papillary RCC, comprising 15% of RCCs.
- Nearly all pharmacological interventions are administered in metastatic RCC. Sutent may occasionally be prescribed as a postoperative adjuvant therapy in locoregional disease, but the typical approach is nephrectomy alone.
- Patients receiving first-line treatment are organized by prognostic risk criteria, as determined by several clinical parameters. This is used to stratify patients into poor, intermediate, and favorable risk categories, which subsequently guide physicians in choosing the appropriate treatment regimen.
- Currently the most prominent drug class in RCC is tyrosine kinase inhibitors (TKIs). While Nexavar inhibits both intracellular and cell surface kinases, other agents (Sutent, Votrient, Lenvima, Cabometyx, and Inlyta) block members of the receptor tyrosine kinase (RTK) superfamily associated with angiogenesis and tumor cell proliferation, most notably VEGFR and PDGFR. In addition to targeting VEGFR/PDGFR, Cabometyx targets the RTKs MET and AXL. Inlyta and Tivopath, on the other hand, are specific for members of the VEGFR family.
- Other drug classes in RCC include inhibitors of the mammalian target of rapamycin (mTOR), a serine-threonine kinase. The mTOR pathway is dysregulated in several human cancers, and Afinitor (an mTOR inhibitor) was the first pharmacological agent available as a therapy for subsequent-line metastatic RCC. Inhibition of mTOR has also been shown to reduce expression of VEGF.
- PD-1 antagonist Opdivo was the first immune checkpoint inhibitor (ICI) approved in RCC and has quickly become a standard of care (SOC) in many treatment settings following demonstrable clinical benefits over earlier therapies. Recently, the agent has been challenged in first-line ccRCC by rival PD-1/PD-L1 antagonists Keytruda and Bavencio, but remains the only drug of its class in subsequent-line settings.
- Combinations dominate in first-line ccRCC. Opdivo is approved in combination with Yervoy, and recently reported positive Phase III results in combination with Cabometyx. Keytruda and Bavencio are approved in combination with Inlyta.
- Sutent is set to lose ground to both newer and more effective treatments, and to imminent biosimilar erosion. Previously the SOC across many treatment settings, the pivotal trials of several newer therapies, which include checkpoint inhibitors Keytruda, Opdivo, and Bavencio, and the RTK inhibitor Cabometyx, have demonstrated significant clinical benefit over Sutent in the first-line setting. Keytruda and Cabometyx have demonstrated benefit over Sutent in subsequent-line settings.
- Sutent may soon be displaced by the prospective label expansions of several ICIs into the adjuvant setting of locoregional disease, where it has largely been able to avoid competition. Approval in this setting has proven difficult, with several other TKIs previously failing to expand into the setting. Due to concern over its risk-benefit profile, Sutent is only listed as a Category 3 treatment in this setting by the NCCN, and was rejected by the EMA. It is thus infrequently administered. Phase III trials of ICIs Keytruda, Opdivo, and Tecentriq are ongoing and, if positive, one or more of these agents could finally displace Sutent and perhaps renew interest in adjuvant treatment of locally advanced RCC.
- Sutent, along with Cabometyx, remains commonly prescribed in first-line non-ccRCC, although this is partly due to a lack of data for newer treatments in the more uncommon histological subtypes of RCC. Opdivo and Yervoy are the only checkpoint inhibitors available in this setting but are only recommended for sarcomatoid RCCs.
- mTOR inhibitors along with most TKI monotherapies are being gradually eclipsed in metastatic RCC by ICI-based combination therapies. However, some TKIs will be able to retain market share through incorporation into these combination regimens. This has been the case with Inlyta, which has seen improved uptake through use in first-line combination therapies that also incorporate checkpoint inhibitors Keytruda and Bavencio.
- A minority of other TKIs are also well poised to improve uptakes through use as combination therapies alongside checkpoint inhibitors, in a similar manner to Inlyta. Already well appraised as a monotherapy in second-line disease, it has prospective label expansions as a combination therapy alongside Opdivo, Tecentriq, and pipeline histone deacetylase inhibitor abexinostat. Similarly, Lenvima, presently available either as a monotherapy or a combination therapy with everolimus, may also be employed in the coming years in a combination therapy alongside Keytruda.
- Many older drugs are subject to patent expiries. VEGF inhibitor Avastin is already facing biosimilar erosion, and the mTOR inhibitor Afinitor has been widely genericized. Other drugs set to follow in the near future include mTOR inhibitor Torisel along with TKIs Sutent, Nexavar, and Votrient.
- Pipeline therapies of note include the PD-L1 inhibitor Tecentriq and potential first-in-class launches of the HIF-2α antagonist MK-6482 and glutaminase antagonist telaglenastat.
9 DISEASE BACKGROUND
9 Risk factors
11 Patient segmentation
13 Referral patterns
13 Recommended pharmacological therapy for locoregional disease
13 Recommended first-line regimens for metastatic ccRCC
14 Preferred subsequent-line regimens for metastatic ccRCC
15 Preferred pharmacological therapy for metastatic non-ccRCC
18 Incidence methodology
22 MARKETED DRUGS
28 PIPELINE DRUGS
36 KEY REGULATORY EVENTS
36 Second Submission for Aveo Pharmaceuticals’ Targeted Therapy, Tivozanib
36 Mylan Reveals FDA Goal Date for Bevacizumab
36 NICE Rejects Keytruda/Inlyta Combo First-Line In RCC
36 EMA OKs Seven New Drugs But Delivers Another Blow To Emmaus
37 US FDA Approval Actions To Watch Out For In June
38 PROBABILITY OF SUCCESS
39 LICENSING AND ASSET ACQUISITION DEALS
39 Zydus Cadila Joins IO Therapy League With XOMA Tie-up
39 IO-Focused CoImmune, Formula Merge In All-Stock Deal
39 Immuno-Oncology Continues To Draw Pharma Companies To The Deal Table
39 Deals Shaping the Medical Industry, July 2019
40 Merck Buys Peloton On Eve Of IPO, Expands Kidney Cancer Portfolio
41 CLINICAL TRIAL LANDSCAPE
42 Sponsors by status
43 Sponsors by phase
44 Recent events
45 DRUG ASSESSMENT MODEL
50 MARKET DYNAMICS
51 FUTURE TRENDS
51 TKIs will remain a common prescribing option when used in combination
51 Sutent poised to lose status as SOC
52 Patients resistant to anti-PD-1/PD-L1 therapy may have more options
52 Competition in first-line metastatic ccRCC will intensify
52 Race for ICI launch in adjuvant treatment of locally advanced tumors
54 CONSENSUS FORECASTS
56 RECENT EVENTS AND ANALYST OPINION
56 MK-6482 for Renal Cell Cancer (May 13, 2020)
57 Opdivo for Renal Cell Cancer (April 20, 2020)
59 Pegilodecakin for Renal Cell Cancer (January 30, 2020)
60 Mavorixafor for Renal Cell Cancer (September 30, 2019)
62 MK-6482 for Renal Cell Cancer (September 29, 2019)
63 Intuvax for Renal Cell Cancer (September 25, 2019)
64 Tivopath for Renal Cell Cancer (September 23, 2019)
65 Tivopath for Renal Cell Cancer (September 10, 2019)
67 Intuvax for Renal Cell Cancer (August 29, 2019)
69 Mavorixafor for Renal Cell Cancer (July 17, 2019)
70 Mvasi for Renal Cell Cancer (June 25, 2019)
71 Telaglenastat for Renal Cell Cancer (June 17, 2019)
72 Tivopath for Renal Cell Cancer (June 3, 2019)
73 MK-6482 for Renal Cell Cancer (May 21, 2019)
75 KEY UPCOMING EVENTS
76 KEY OPINION LEADER INSIGHTS
77 UNMET NEEDS
78 Prescription information
LIST OF FIGURES
12 Figure 1: AJCC Prognostic Groups for RCC
12 Figure 2: Definitions of the diagnostic criteria for primary tumor (T), regional lymph nodes (N), and distant metastasis (M) in kidney cancer
14 Figure 3: First-line therapy for ccRCC
15 Figure 4: Subsequent-line therapy for RCC
16 Figure 5: First-line therapy for non-ccRCC
20 Figure 6: Trends in incident cases of renal cell carcinoma, 2018–27
28 Figure 7: Overview of pipeline drugs for renal cell carcinoma in the US
28 Figure 8: Pipeline drugs for renal cell carcinoma, by company
29 Figure 9: Pipeline drugs for renal cell carcinoma, by drug type
29 Figure 10: Pipeline drugs for renal cell carcinoma, by classification
38 Figure 11: Probability of success in the renal cell carcinoma pipeline
41 Figure 12: Clinical trials in renal cell carcinoma
41 Figure 13: Top 10 drugs for clinical trials in renal cell carcinoma
42 Figure 14: Top 10 companies for clinical trials in renal cell carcinoma
42 Figure 15: Trial locations in renal cell carcinoma
43 Figure 16: Renal cell carcinoma trials status
44 Figure 17: Renal cell carcinoma trials sponsors, by phase
45 Figure 18: Datamonitor Healthcare’s drug assessment summary for renal cell carcinoma
50 Figure 19: Market dynamics in renal cell carcinoma
51 Figure 20: Future trends in renal cell carcinoma
57 Figure 21: MK-6482 for Renal Cell Cancer (May 13, 2020): Phase II – VHL-Associated RCC
59 Figure 22: Opdivo for Renal Cell Cancer (April 20, 2020): Phase III – CheckMate 9ER (w/Cabozantinib)
62 Figure 23: Mavorixafor for Renal Cell Cancer (September 30, 2019): Phase I/IIa – w/Axitinib (RCCA)
65 Figure 24: Tivopath for Renal Cell Cancer (September 23, 2019): Phase Ib/II – TiNivo (w/Opdivo)
67 Figure 25: Tivopath for Renal Cell Cancer (September 10, 2019): Phase III – TIVO-3
69 Figure 26: Intuvax for Renal Cell Cancer (August 29, 2019): Phase II – MERECA
72 Figure 27: Telaglenastat for Renal Cell Cancer (June 17, 2019): Phase II – ENTRATA (w/Everolimus)
75 Figure 28: Key upcoming events in renal cell carcinoma
77 Figure 29: Unmet needs in renal cell carcinoma
LIST OF TABLES
17 Table 1: Preferred/recommended branded treatment regimens for patients with RCC
19 Table 2: Incident cases of renal cell carcinoma, 2018–27
21 Table 3: Incident cases of renal cell carcinoma, by gender, 2018
23 Table 4: Marketed drugs for renal cell carcinoma
30 Table 5: Pipeline drugs for renal cell carcinoma
54 Table 6: Historical global sales, by drug ($m), 2015–19
55 Table 7: Forecasted global sales, by drug ($m), 2020–24
56 Table 8: MK-6482 for Renal Cell Cancer (May 13, 2020)
58 Table 9: Opdivo for Renal Cell Cancer (April 20, 2020)
60 Table 10: Pegilodecakin for Renal Cell Cancer (January 30, 2020)
61 Table 11: Mavorixafor for Renal Cell Cancer (September 30, 2019)
62 Table 12: MK-6482 for Renal Cell Cancer (September 29, 2019)
63 Table 13: Intuvax for Renal Cell Cancer (September 25, 2019)
64 Table 14: Tivopath for Renal Cell Cancer (September 23, 2019)
66 Table 15: Tivopath for Renal Cell Cancer (September 10, 2019)
68 Table 16: Intuvax for Renal Cell Cancer (August 29, 2019)
69 Table 17: Mavorixafor for Renal Cell Cancer (July 17, 2019)
70 Table 18: Mvasi for Renal Cell Cancer (June 25, 2019)
71 Table 19: Telaglenastat for Renal Cell Cancer (June 17, 2019)
73 Table 20: Tivopath for Renal Cell Cancer (June 3, 2019)
74 Table 21: MK-6482 for Renal Cell Cancer (May 21, 2019)
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