MMIT Reality Check on Colorectal Cancer (4Q2023)
Payer Coverage:
A review of market access for colorectal cancer treatments shows that under the pharmacy benefit, about 51% of the lives under commercial formularies are covered with utilization management restrictions. Around 41% of the lives under Medicare formularies are not covered for at least one of the drugs.
Under the medical benefit, about 64% of the lives under commercial policies are covered with utilization management restrictions. Almost 53% of the lives under Medicare Part B policies have access to at least one of the drugs without utilization management restrictions.
For about 93% of the covered lives, payer pharmacy benefit formularies do not require step therapy (ST). Of the lives that require ST, 18% require multiple steps. Around 74% of payer-controlled pharmacy benefit covered lives require prior authorization, with 8% of those lives covered by policies that are restrictive as compared with a product’s FDA-approved label.
Trends:
FDA Approves Fruzaqla
In November 2023, the FDA approved Takeda Pharmaceuticals U.S.A., Inc.’s Fruzaqla (fruquintinib) for the treatment of adults with metastatic colorectal cancer (mCRC) who have been treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) therapy and, if Rat sarcoma (RAS) wild-type and medically appropriate, an anti-epidermal growth factor receptor (EGFR) therapy. The agent is the first FDA-approved selective inhibitor of all three VEGF receptor kinases for previously treated mCRC regardless of biomarker status. The agency gave the drug priority review. Dosing for the capsule is 5 mg once daily for the first 21 days of each 28-day cycle.
FDA Gives Lonsurf Additional Indication
In August 2023, the FDA gave an additional indication to Taiho Pharmaceutical Co., Ltd. division Taiho Oncology, Inc.’s Lonsurf (trifluridine/tipiracil) as a single agent or in combination with bevacizumab for the treatment of adults with metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) drug and, if Rat sarcoma (RAS) wild-type, an anti-epidermal growth factor receptor (EGFR) therapy. The agency first approved the oral nucleoside antitumor agent on Sept. 22, 2015. The newest use had priority review. Dosing for the tablet is 35 mg/m2 twice daily on days one through five and days eight through 12 of each 28-day cycle. Drugs.com lists the price of 20 6.14 mg/15 mg tablets as more than $4,204.
FDA Broadens Lonsurf Use in Colorectal Cancer
The FDA granted another approval to Taiho Pharmaceutical Co., Ltd. division Taiho Oncology, Inc.’s Lonsurf (trifluridine/tipiracil) in combination with another agent for a type of colorectal cancer. The decision provides another treatment option for a condition that respondents to a Zitter Insights survey regard as in need of more effective therapies.
Key Findings:
Market Events Drive Changes
In November 2023, the FDA approved Takeda Pharmaceuticals U.S.A., Inc.’s Fruzaqla (fruquintinib) for the treatment of adults with metastatic colorectal cancer (mCRC) who have been treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) therapy and, if Rat sarcoma (RAS) wild-type and medically appropriate, an anti-epidermal growth factor receptor (EGFR) therapy. In August 2023, the agency gave an additional indication to Taiho Pharmaceutical Co., Ltd. division Taiho Oncology, Inc.’s Lonsurf (trifluridine/tipiracil) as a single agent or in combination with bevacizumab for use in the same indication. In January 2023, the FDA granted accelerated approval to Seagen Inc.’s Tukysa (tucatinib) in combination with trastuzumab for the treatment of adults with RAS wild-type, human epidermal growth factor receptor 2-positive (HER2+) unresectable or mCRC that has progressed following treatment with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy.
Competitive Market Landscape
Combinations of chemotherapy and bevacizumab, either as branded Avastin from Roche Group member Genentech USA, Inc. or in biosimilar form, have managed to remain a standard of care (SoC) in the highly crowded first- and second-line settings. Uptake also remains high for Eli Lilly and Co.’s Erbitux (cetuximab), which is a SoC for first- and second-line rapidly accelerated fibrosarcoma/Kirsten Rat sarcoma (RAF/KRAS) wild-type and EGFR+ tumors (approximately 40% of CRCs). Subsequently approved anti-angiogenic competitors to Avastin and Erbitux, such as Sanofi’s Zaltrap (ziv-aflibercept) and Amgen Inc.’s Vectibix (panitumumab), respectively, have had only limited impacts. All branded drugs are approved solely in metastatic, unresectable disease. Most treatment regimens in mCRC consist of a chemotherapy and angiogenesis inhibitor combination. Anti-programmed death receptor-1 (PD-1) immune checkpoint inhibitors Opdivo (nivolumab) from Bristol Myers Squibb and Keytruda (pembrolizumab) from Merck & Co., Inc. have seen initial success in microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) CRCs, which comprise approximately 15% of patients. Genentech’s Herceptin (trastuzumab), Tykerb (lapatinib) from Novartis Pharmaceuticals Corp. and Perjeta (pertuzumab), also from Genentech, are recommended for off-label use in HER2+ tumors (approximately 3.5% of CRCs in the U.S.). There is some preference for Lonsurf in the newer oral agents, but this may be due to National Comprehensive Cancer Network (NCCN) recommendations rather than contracting.
Pharmacy, Medical Benefit Implications
Although colorectal cancer drugs primarily are covered under the medical benefit, payers and PBMs have included injectable cancer medications in their formularies in effort to control cost of care and improve patient disease management. Most policies require the use of generic chemotherapy regimens FOLFOX, FOLFOXIRI or CapeOX before newer targeted agents. Genetic testing is required for most targeted agents. Primarily covered under the medical benefit, systemic therapy is administered in local disease, typically as adjuvant therapy, mostly consisting of generic chemotherapies. Most branded agents are confined to metastatic, unresectable CRC. Treatment for mCRC is heavily dependent on gene expression, with many drugs being prescribed only for specific tumor profiles. Some of these agents, like Pfizer Inc.’s Braftovi (encorafenib), will process through the pharmacy benefit.
Key Players in Market:
