MMIT Reality Check on Colorectal Cancer (4Q2022)

Payer Coverage:

A review of market access for colorectal cancer treatments shows that under the pharmacy benefit, about 50% of the lives under commercial formularies are covered with utilization management restrictions. Around 45% of the lives under Medicare formularies are not covered for at least one of the drugs.

Under the medical benefit, about 74% of the lives under commercial policies are covered with utilization management restrictions. Almost 51% 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 75% of payer-controlled pharmacy benefit covered lives require prior authorization, with 7% of those lives covered by policies that are restrictive as compared with a product’s FDA-approved label.

Trends:

FDA Approves Vegzelma

In September 2022, the FDA approved Celltrion USA’s Vegzelma (bevacizumab-adcd) for the treatment of multiple indications: (1) metastatic colorectal cancer, in combination with intravenous fluorouracil-based chemotherapy for first- or second-line treatment; (2) metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line bevacizumab product-containing regimen; (3) unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer, in combination with carboplatin and paclitaxel for first-line treatment; (4) recurrent glioblastoma in adults; (5) metastatic renal cell carcinoma in combination with interferon alfa; (6) persistent, recurrent or metastatic cervical cancer, in combination with paclitaxel and cisplatin, or paclitaxel and topotecan; (7) epithelial ovarian, fallopian tube or primary peritoneal cancer, in combination with carboplatin and paclitaxel, followed by Vegzelma as a single agent, for stage III or IV disease following initial surgical resection or in combination with paclitaxel, pegylated liposomal doxorubicin or topotecan for platinum-resistant recurrent disease who received no more than two prior chemotherapy regimens or in combination with carboplatin and paclitaxel or carboplatin and gemcitabine, followed by Vegzelma as a single agent, for platinum-sensitive recurrent disease. The agent is the fourth FDA-approved biosimilar of Avastin (bevacizumab) from Genentech USA, Inc., a member of the Roche Group. Dosing for the vascular endothelial growth factor inhibitor varies according to the indication. Drugs.com lists the price of one 100 mg/4 mL (25 mg/mL) of Avastin as more than $848.

FDA Approves Alymsys

In April 2022, the FDA approved Amneal Pharmaceuticals, Inc.’s Alymsys (bevacizumab-maly) for the treatment of multiple conditions: (1) first- or second-line treatment of metastatic colorectal cancer in combination with intravenous fluorouracil-based chemotherapy; (2) second-line treatment of metastatic colorectal cancer in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin chemotherapy in people who have progressed on a first-line bevacizumab product; (3) first-line treatment of unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer in combination with carboplatin and paclitaxel; (4) recurrent glioblastoma in adults; (5) metastatic renal cell carcinoma in combination with interferon alfa; (6) persistent, recurrent or metastatic cervical cancer in combination with paclitaxel and cisplatin or paclitaxel and topotecan; and (7) epithelial ovarian, fallopian tube or primary peritoneal cancer in combination with paclitaxel, pegylated liposomal doxorubicin or topotecan for platinum-resistant recurrent disease in people receiving no more than two prior chemotherapy regimens. The vascular endothelial growth factor inhibitor is the third biosimilar of Roche Group member Genentech USA, Inc.’s Avastin (bevacizumab) that the agency has approved. Dosing of the intravenous infusion is based on indication.

FDA Gives Erbitux Plus Braftovi Additional Approval

In September 2021, the FDA approved a new indication for Eli Lilly and Co.’s Erbitux (cetuximab) in combination with Pfizer, Inc.’s Braftovi (encorafenib) to treat adults with metastatic colorectal cancer with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy. The agency first approved Erbitux on Feb. 12, 2004. Dosing is a 120-minute intravenous infusion of Erbitux 400 mg/m2, followed by a 60-minute infusion 250 mg/m2 weekly and 300 mg once daily of Braftovi. Drugs.com lists the price of 2 mg/mL of Erbitux as more than $733.00 and 120 75 mg capsules of Braftovi as more than $13,243.00.

Key Findings:

Market Events Drive Changes

In September 2022, the FDA approved Celltrion USA’s Vegzelma (bevacizumab-adcd) for the treatment of multiple indications, including (1) metastatic colorectal cancer, in combination with intravenous fluorouracil-based chemotherapy for first- or second-line treatment, and (2) metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in patients who have progressed on a first-line bevacizumab product-containing regimen. In April 2022, the agency approved Amneal Pharmaceuticals, Inc.’s Alymsys (bevacizumab-maly) for the treatment of multiple conditions, including (1) first- or second-line treatment of metastatic colorectal cancer in combination with intravenous fluorouracil-based chemotherapy, and (2) second-line treatment of metastatic colorectal cancer in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin chemotherapy in people who have progressed on a first-line bevacizumab product. The drugs are the third and fourth FDA-approved biosimilars of Roche Group member Genentech USA, Inc.’s Avastin (bevacizumab).

Competitive Market Landscape

Combinations of chemotherapy and bevacizumab, either as branded Avastin 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 Erbitux, which is a SoC for first- and second-line RAF/KRAS WT and EGFR+ tumors (approximately 40% of colorectal cancers (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 metastatic CRC (mCRC) consist of a chemotherapy and angiogenesis inhibitor combination. Anti PD-1 immune checkpoint inhibitors Opdivo (nivolumab) from Bristol Myers Squibb and Keytruda (pembrolizumab) from Merck & Co., Inc. have seen initial success in MSI-H/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.).

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 since oncology is a Medicare-protected class, and therefore coverage is surfacing under the pharmacy benefit as well for Part B vs. Part D determination. Most policies require the use of generic 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 Braftovi, will process through the pharmacy benefit. First- and second-line metastatic CRC have become very crowded treatment settings, with multiple combinations of chemotherapies and targeted agents competing for the same disease mutation.

Key Players in Market:

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