Three Biosimilars Entering US Oncology Market at Substantial Discounts

Mark D. Pegram, MD, associate director for clinical research, Stanford Comprehensive Cancer Institute

Mark D. Pegram, MD

Three biosimilars—bevacizumab-bvzr (Zirabev), rituximab-pvvr (Ruxience), and trastuzumab-qyyp (Trazimera)—will become available in the United States at a substantial discount to their reference products bevacizumab (Avastin), rituximab (Rituxan), and trastuzumab (Herceptin), respectively, according to an announcement made by Pfizer.¹

The agents are expected to launch at the lowest wholesale acquisitions cost (WAC) among the originator products already on the market.

“We’re proud to expand our leading biosimilars portfolio by launching these 3 treatments, which can potentially create a significant savings for the US healthcare system while increasing access to critical therapies,” Angela Lukin, regional president, North America Oncology at Pfizer, commented in the press release. “We look forward to working with payers and providers to deliver these important medicines to patients who are living with certain cancers and autoimmune conditions.”

Bevacizumab-bvzr

Bevacizumab-bvzr was the first of the 3 to be introduced to the US market on December 31, 2019. The product launched at a WAC of $61.34 per 10 mg, which translates to a 23% reduction in cost compared with the WAC of its originator product, bevacizumab.

In June 2019, the biosimilar received approval from the FDA for the treatment of patients with the following cancers: metastatic colorectal cancer; unresectable, locally advanced, recurrent or metastatic nonsquamous non—small cell lung cancer (NSCLC); recurrent glioblastoma; metastatic renal cell carcinoma; and persistent, recurrent, or metastatic cervical cancer.

The approval followed an examination of a comprehensive data package which indicated biosimilarity between bevacizumab-bvzr and bevacizumab. These data included findings from the REFLECTIONS B7391003 trial, which was a clinical comparative study that proved clinical equivalence between the 2 agents when used in patients with advanced nonsquamous NSCLC. No clinically meaningful differences were observed between the products.²

Results from the trial presented at the 2018 ASCO Annual Meeting demonstrated that the relative risk of objective response rate (ORR) was 1.015, and the 90% confidence interval (0.886-1.163) was contained within the therapeutic equivalence margin of 0.73 to 1.37, which was prespecified by the FDA.³ With regard to safety, the rate of treatment-emergent adverse events between the biosimilar and the reference product were similar, at 96.6% and 96.1%, respectively.

Rituximab-pvvr

The biosimilar product rituximab-pvvr, which was introduced to the US market today, was launched at a WAC of $71.68 per 10 mg, which translates to a 24% discount to the WAC of the reference product, rituximab, according to the announcement.

The biosimilar was approved for the treatment of adult patients with CD20-positive B-cell non-Hodgkin lymphoma as a single agent or in combination with chemotherapy, or for those with CD20-positive chronic lymphocytic leukemia in July 2019. The product was also indicated for use in patients with granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA).

The regulatory decision was based on a review of a comprehensive data package which showed biosimilarity between the 2 products. Data from the clinical comparative REFLECTIONS B3281006 trial were included in the package and demonstrated that there were no clinically meaningful differences between the 2 products with regard to safety and efficacy in patients with CD20-positive follicular lymphoma with low tumor burden.⁴

Specifically, treatment with rituximab-pvvr was shown to lead to an ORR of 75.5% at week 26 of treatment compared with 70.7% with rituximab-EU, which translated to a difference of 4.66%. The corresponding 95% CI (-4.16-13.47) was found to be within the FDA’s prespecified equivalence margin of ±16%.

The complete response rates with the biosimilar and the reference product were 29.3% versus 30.4%, respectively, and the stable disease rate was 11.5% versus 19.6%. Only 3.4% of patients on the biosimilar arm experienced disease progression compared with 4.3% of those on the reference-product arm. The estimated 1-year PFS rates were 76.4% (95% CI, 67.2-83.4) with the biosimilar compared with 81.2% (95% CI, 72.1-87.6) with the reference product.

Trastuzumab-qyyp

The biosimilar trastuzumab-qyyp will be the last of the 3 products to be made available, according to the press release. This agent will be introduced to the market on February 15, 2020, at a WAC of $80.74 per 10 mg, which translates to a 22% discount to the WAC of trastuzumab, the originator product.

The biosimilar will be available for use in the treatment of patients with HER2-overexpressing breast cancer as well as those with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma.

Trastuzumab-qyyp was the fourth trastuzumab biosimilar to receive approval from the FDA in March 2019 based on findings from a comprehensive data package which included data from the phase III REFLECTIONS B327-02 trial. Findings from the trial proved that treatment with the 2 products led to similar safety and efficacy outcomes in the patients who received them.

The biosimilar achieved equivalence in ORR versus trastuzumab, according to data from the trial presented at the 2017 ESMO Congress.⁵ Specifically, the risk ratio was 0.940 with a 95% CI of 0.842 to 1.049, thus achieving the prespecified equivalence margin of 0.8 to 1.25. Additionally, the 1-year PFS with trastuzumab-qyyp was 56% compared with 52% with trastuzumab-EU. The 1-year overall survival rates with the biosimilar and reference product were 88.84% and 87.96%, respectively. No new safety signals were observed and the toxicity profiles of the 2 products proved to be similar.

Data from the substudy, REFLECTIONS B327-04, published in the British Journal of Cancer in July 2018 proved clinical equivalence between the 2 products with regard to safety and efficacy in women with operable HER2-positive breast cancer.⁶

Looking Ahead

Pass-through status is being pursued by Pfizer for all 3 of the biosimilars; this program supports reimbursement and incentivizes access to certain treatments for patients with Medicare.

“The introduction of 3 new biosimilars is significant, delivering additional treatment options for patients across 9 cancer types,” Mark D. Pegram, MD, associate director for clinical research, Stanford Comprehensive Cancer Institute, and director, Breast Oncology Program, Stanford Women’s Cancer Center, stated in the press release. “Biosimilars can play an important role in the care of people living with cancer, and I am encouraged by the possibility for improved access for providers to these medicines which are highly similar to their reference product.”

References

1. Pfizer brings three new biosimilars to US patients at substantial discounts [news release]. Pfizer Inc; January 23, 2020. go.aws/2GjTwYg. Accessed January 23, 2020.
2. Pfizer receives US FDA approval for its oncology biosimilar, Zirabev (bevacizumab-bvzr) [news release]. Pfizer Inc; June 28, 2019. bit.ly/3az1x9M. Accessed January 23, 2020.
3. Socinski MA, Pawel JV, Kasahara K, et al. A comparative clinical study of PF-06439535, a candidate bevacizumab biosimilar, and reference bevacizumab, in patients with advanced non-squamous non-small cell lung cancer. J Clin Oncol. 2018;36(suppl 15; abstr 109). doi: 10.1200/JCO.2018.36.15_suppl.109.
4. FDA approves Pfizer’s biosimilar, Ruxience (rituximab-pvvr), for certain cancers and autoimmune conditions [news release]. Pfizer Inc; July 23, 2019. bit.ly/2usLycC. Accessed January 23, 2020.
5. Pegram M, Tan-Chiu E, Freyman A, et al. A randomized, double-blind study of PF-05280014 (a potential trastuzumab biosimilar) vs trastuzumab, both in combination with paclitaxel, as first-line treatment for HER2-positive metastatic breast cancer. Ann Oncol. 2017;28(suppl 5; abstr 238PD). doi: 10.1093/annonc/mdx365.001a.
6. Lammers PE, Dank M, Masetti R, et al. Neoadjuvant PF-05280014 (a potential trastuzumab biosimilar) versus trastuzumab for operable HER2+ breast cancer. Br J Cancer. 2018;119(3):266-273. doi: 10.1038/s41416-018-0147-1.