Emerging biosimilars market presents opportunities and challenges

Biosimilars in development

While numerous other biosimilars of filgrastim and pegfilgrastim are in development, the major focus has been on the development of more biosimilars to treat cancer (Table 3). BLAs have been submitted for 4 biosimilars of trastuzumab and 1 bevacizumab biosimilar. Approval for several of the trastuzumab biosimilars has been delayed by CRLs from the FDA, mostly regarding issues with the manufacturing process or facility. Several other trastuzumab and bevacizumab biosimilars are in late-stage clinical trials.

The results of several phase 3 comparative clinical trials were recently published or reported at annual conferences. Pfizer’s PF-05280014 was compared with the European Union (EU)–approved trastuzumab, both in combination with paclitaxel, in patients with previously untreated HER2-positive metastatic breast cancer. Data reported at the European Society for Medical Oncology congress in 2017 demonstrated equivalence between the reference product and biosimilar in overall response rate (ORR).²³

Another recently published trial compared this biosimilar to EU-trastuzumab, both in combination with carboplatin and docetaxel, as neoadjuvant treatment for patients with resectable HER2-positive breast cancer. Among 226 patients randomized to receive 8 mg/kg in cycle 1 and 6 mg/kg thereafter of the biosimilar or reference product, every 3 weeks for 6 cycles, the pathologic complete response (pCR) rates were 47% and 50%, respectively.²⁴

The results of a phase 3 study comparing Samsung Bioepis/Merck’s joint offering SB3 were recently published. A total of 875 patients were randomized 1:1 to receive SB3 or reference trastuzumab in combination with chemotherapy (4 cycles docetaxel followed by 4 cycles 5-fluorouracil/epirubicin/cyclophosphamide) prior to surgery, followed by 10 cycles of adjuvant SB3 or trastuzumab reference. Rates of event-free survival (EFS) were comparable between the 2 groups at 12 months (93.7% vs 96.1%, respectively).²⁵

Amgen’s ABP980 was evaluated in the phase 3 LILAC trial, which measured the effect of the biosimilar on pCR in women with HER2-positive early breast cancer compared with reference trastuzumab. After 4 cycles of run-in anthracycline-based chemotherapy, ABP980 or reference trastuzumab were administered in combination with paclitaxel. This was followed by surgery and then ABP980 or reference trastuzumab in the adjuvant setting for up to 1 year, with the option to continue on the same drug as the neoadjuvant setting or to switch to the other. Among 696 assessable patients, the pCR rates were 48% and 42%, respectively.²⁶

Most advanced in clinical testing among the upcoming bevacizumab biosimilars is Pfizer’s PF-06439535, for which the results of a phase 3 comparative trial were presented at the 2018 annual meeting of the American Society for Clinical Oncology. PF-06439535 was compared with the EU-approved bevacizumab, both in combination with paclitaxel and carboplatin, as first-line therapy for patients with advanced non-squamous NSCLC. Among 719 patients, the primary endpoint of ORR was 45.3% and 44.6%, respectively.²⁷

Biosimilars of a third blockbuster cancer drug, the CD20-targeting mAb rituximab (Rituxan) are also in development and FDA approval is pending for 2. The patent for Rituxan expired in 2016, so these drugs could hit the market as soon as they are approved.

In a race to the finish for the first US-approved rituximab biosimilar, Celltrion-Teva’s CT-P10 (Truxima) seems most likely to come first; the Oncologic Drugs Advisory Committee voted unanimously in October 2018 to recommend its approval. Phase 3 comparative data were recently published; patients with newly diagnosed advanced-stage follicular lymphoma were randomized to receive intravenous infusions of 375 mg/m² CT-P10 or reference rituximab, both in combination with cyclophosphamide, vincristine, and prednisone, on day 1 of 8 21-day cycles. The ORRs were identical (92.6%) for both drugs, pharmacokinetics data also suggested bioequivalence, and the incidence of AEs was also comparable (83% vs 80%).²⁸

Biosimilars of the epidermal growth factor receptor (EGFR)-targeting mAb cetuximab are also listed in the pipeline for several biosimilar developers, but there is no indication of their developmental status as yet and no clinical trials are ongoing in the US.

Sorrento is developing STI-001, a cetuximab biosimilar, and reported that a phase 3 trial had been completed. Instead of a comparison with the reference product, however, the trial compared STI-001 in combination with irinotecan with irinotecan alone. They reported significantly higher ORR, PFS, and OS with the biosimilar compared with irinotecan alone, and a significant increase over historical data with the reference product, as well as fewer side effects and immunogenicity, which they attribute to its manufacture in a different cell line. However, no data has been published and no trials are ongoing in the United States, so the status of its development remains unclear.²⁹