Fotivda Approval Provides New Option for Certain People With Renal Cell Carcinoma

The renal cell carcinoma (RCC) therapeutic class boasts multiple agents, but a recent entrant is offering a new tool for certain patients. A Zitter Insights survey shows that the majority of oncologist respondents are likely to prescribe Aveo Oncology’s Fotivda (tivozanib) for advanced RCC.

On March 10, the FDA approved Fotivda for the treatment of adults with relapsed or refractory advanced RCC who have received at least two prior systemic therapies. It is the first FDA-approved therapy for this use.

The recommended dose of the oral, next-generation vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) is 1.34 mg once daily for 21 days every 28 days on treatment, followed by seven days off. The capsule’s monthly list price is $24,150. According to an Aveo slide deck, that price compares to those of other relapsing or refractory RCC options: Pfizer Inc.’s Inlyta (axitinib) is $16,628 per treatment cycle, Bayer’s Nexavar (sorafenib) is $20,760, Exelixis, Inc.’s Cabometyx (cabozantinib) is $21,663, and the combination of Eisai Inc.’s Lenvima (lenvatinib) plus Novartis Pharmaceuticals Corp.’s Afinitor (everolimus) is $37,505.

For the Managed Care Oncology Index: Q4 2020, from Dec. 2, 2020, to Jan. 5, 2021, Zitter Insights polled 40 commercial payers with 132.0 million covered lives. Payers with 84% of lives expected they would manage the drug to label, while those with 10% of lives anticipated covering it more restrictively than its label. Respondents with 6% of lives expected that they would not require prior authorization for Fotivda. None of the payers anticipated not covering the drug.

Zitter Insights and AIS Health are both MMIT companies.

The drug’s approval was based on a handful of clinical trials, including TIVO-3, a Phase III study pitting it against Nexavar. Payers covering 40% of lives said they are likely to use Fotivda to negotiate greater discounts for Nexavar, but those with 42% of lives said they are unlikely to take that action. Those covering 78% of lives do not expect to prefer Fotivda over Nexavar in advanced RCC and do not anticipate incentivizing oncologists to prescribe Fotivda over Nexavar.

Zitter Insights also surveyed 100 oncologists during the same time frame. Almost 70% said they were likely to prescribe Fotivda for advanced RCC, as well as prescribe it over Nexavar (see chart below). Respondents were fairly evenly divided on whether they would refrain from prescribing Nexavar.

“With advances in RCC treatment, patients are living longer, increasing the need for proven, well-tolerated treatment options in the relapsed or refractory setting,” said Brian Rini, M.D., chief of clinical trials at Vanderbilt Ingram Cancer Center and principal investigator of the TIVO-3 trial, in an Aveo press release. “The TIVO-3 study is the first positive Phase 3 study in RCC patients who received two or more prior systemic therapies, and also the first Phase 3 RCC study to include a predefined population of patients who have received prior immunotherapy, the current standard of care in earlier-line treatment. With this approval, I believe Fotivda represents an attractive intervention, and expect it to play a meaningful role in the evolving RCC treatment landscape.”

When it comes to the RCC class in general, any management of it “will be limited to approved indications for the medications being utilized or consistency with the accepted treatment guidelines,” such as those from the National Comprehensive Cancer Network (NCCN) or the American Society of Clinical Oncology (ASCO), says Winston Wong, Pharm.D., president of W-Squared Group. “It was not that long ago that RCC was one of the most difficult cancers to treat. The effectiveness of immunotherapy as a treatment option has changed the landscape significantly. True management of this cancer type would only be present in plans with pathway programs in place, and, even then, management would most likely be found for early and first- or second-line advanced disease. Fotivda is the first option for third-line or later RCC disease, based upon the TIVO-3 trial.”

In that trial, points out Mesfin Tegenu, CEO of RxParadigm, “Fotivda was able to show improved progression-free survival compared to sorafenib. However, Fotivda fell short in showing overall survival relative to sorafenib. The key takeaway for Fotivda will be its safety profile relative to current therapies for RCC. Therefore, Fotivda may be an option for a subset of patients who have failed previous therapies and require a more tolerable and safe option.”

In addition, Wong points out that “patients who received prior therapy with a checkpoint inhibitor in combination with a VEGF inhibitor or two prior VEGF inhibitors saw the greatest reduction in the risk of progression. Thus, there is now an option for third-line treatment, which would otherwise be a referral to a clinical trial. Response rates were also higher with Fotivda compared to sorafenib. The real question at this point, however, is whether to proceed with a third-line treatment or move on to a clinical trial. Luckily, this would be a determination by the treating oncologist and their patient and not a payer.”

Asked if payers are likely to cover Fotivda, Wong notes that the agent “is a potent, selective inhibitor of VEGFRs [i.e., VEGF receptors] 1, 2 and 3 with a long half-life designed to improve efficacy and tolerability. It would be my expectation that payers will cover Fotivda as a third-line treatment option for advanced RCC since it is consistent with the approved FDA indication, and there is nothing really indicated for this far of an advanced disease. Further strength for coverage will occur if/when the third-line treatment option is included in the NCCN and ASCO guidelines.” (NCCN added Fotivda to its guidelines on March 29, after this interview took place.)

“Sutent (sunitinib malate) has been the longstanding standard of care for renal cell carcinoma treatment,” says Tegenu. “Despite NCCN recently recognizing Fotivda by making updates to the guidelines following the recent FDA approval, plans will continue to monitor its place in therapy similar to the PD-1 [i.e., programmed cell death-1] inhibitors drug class. For example, while PD-1 inhibitors have recently been making moves to being first-line therapy treatments, there continue to be inconsistencies in commercial payer coverage for this class of drugs compared to the TKI, VEGF and mTOR [i.e., mechanistic target of rapamycin] inhibitor classes.”

“The choice of treatment for an advanced RCC patient is mostly determined by their prognostic risk stratification,” Wong explains. “The risk stratification is based upon the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model, based upon Karnofsky performance status, time from first diagnosis to treatment, hemoglobin level, serum calcium, neutrophil count and platelet count.”

RCC has comorbidities that may complicate managing the condition, including obesity, diabetes and cardiovascular-related conditions, points out Tegenu. “Taking into account an individual’s overall health status and other variables (e.g., age and gender) are standard in predicting their outcome; however, there is still work to be done as it relates to individually managing these patients to improve overall survival. With this said, currently there are no standard methods in capturing comorbidities in cancer registries to aid in tracking and monitoring the patients following treatment.”

Observes Wong, “Cancer has a way of complicating any comorbidity, and management of comorbidities will depend largely on the clinical presentation and treatment response.”

It’s been a long road for Fotivda, which the FDA rejected in 2013 for use in first-line RCC. Aveo has explored it in other indications, including breast and colorectal cancer, but without success.

Drug’s Patents Expire Soon

The company holds two patents on tivozanib, one of which expires in April 2022 and the second of which expires in November 2023. In mid-March, though, the company said it intends to file applications for patent term extensions that could push one of those dates back potentially five years.

But if that doesn’t occur, “wide use of this medication may purely be dependent on its clinical value instead of ever-increasing TV ads,” says Tegenu.

Contact Tegenu at Mesfin.Tegenu@rxparadigm.com and Wong at w2sqgroup@gmail.com. For more information on the Zitter data, contact Jill Brown Kettler at jbrown@aishealth.com.

This story was reprinted from AIS Health’s monthly publication RADAR on Specialty Pharmacy. Visit https://aishealth.com/product/specialty-pharmacy.

Angela Maas

Angela has an extensive background of editing, reporting and writing for trade and consumer publications. She has written Radar on Specialty Pharmacy (formerly called Specialty Pharmacy News) since she joined AIS Health in 2005 and has broad knowledge of the various issues at play within the space. Before joining AIS Health, she was managing editor at Employee Benefit News and Employee Benefit News Canada and managing editor at HemAware (a hemophilia publication), Lupus Living and Momentum (a multiple sclerosis publication). She has a B.A. in English and an M.A. in British literature from Arizona State University.

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