Amgen, one of the world's leading independent biotechnology companies, and Allergan plc., a global pharmaceutical company, announced a phase 3 study of biosimilar candidate ABP 215 met its primary and secondary endpoints. The study evaluated the efficacy and safety of ABP 215 compared with Avastin (bevacizumab) in adult patients with advanced non-squamous non-small cell lung cancer (NSCLC).

The primary endpoint, an assessment of objective response rates (ORR), was within the prespecified margin for ABP 215 compared to bevacizumab, showing clinical equivalence. Safety and immunogenicity of ABP 215 were comparable to bevacizumab. Secondary endpoint results were consistent with the primary finding and included risk difference of ORR, duration of response and progression-free survival (PFS).

ABP 215 is being developed as a biosimilar to bevacizumab, a recombinant immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to vascular endothelial growth factor (VEGF) and inhibits the interaction of VEGF with its receptors, VEGF receptor-1 and VEGF receptor-2, thus inhibiting establishment of new blood vessels necessary for the maintenance and growth of solid tumours.

"Amgen is committed to bringing high-quality, reliably supplied medicines to patients and we're excited to leverage our development and manufacturing capabilities in oncology for our biosimilars. The positive phase 3 results from ABP 215 study showed clinical equivalence in efficacy, and comparable safety and immunogenicity, to bevacizumab," said Sean E. Harper, M.D., executive vice president of research and development at Amgen.

"Non-small cell lung cancer is the leading cause of cancer death in both men and women in the US and the EU. ABP 215 holds the potential to advance access to treatment options for oncology patients."

"The positive phase 3 clinical results of ABP 215 mark an important step forward in the development of biosimilar treatment options for patients with advanced non-small cell lung cancer," said David Nicholson, executive vice president and president of global research and development of Allergan.

"Allergan is committed to developing biosimilars that provide safe, high-quality and effective therapies in key disease areas for patients."

Amgen and Allergan are collaborating on the development and commercialisation of four oncology biosimilars. Amgen has a total of nine biosimilars in development. Allergan is also independently developing biosimilars.

This was a randomized, double-blind, active-controlled study (study number 20120265) that evaluated safety and efficacy of ABP 215 compared to bevacizumab in adult patients with advanced non-squamous NSCLC receiving first-line chemotherapy with carboplatin and paclitaxel. There were 642 patients enrolled and randomized (1:1) to receive investigational product (ABP 215 or bevacizumab) at a dose of 15 mg/kg administered as an IV infusion every 3 weeks (Q3W) for up to 6 cycles. Among them, there were 328 patients randomized to the ABP 215 group and 314 patients to the bevacizumab group.

The duration of the treatment included a screening period of up to 4 weeks, followed by up to 6 Q3W treatment cycles and an end of treatment visit 21 days after the last dose of investigational product or study specified chemotherapy. Following the end of treatment visit, patients were followed for disease progression and overall survival (OS) until the end of the clinical study, consent was withdrawn, they were lost to follow-up, death or had proscribed therapy (e.g. commercial bevacizumab, non-study anti-cancer treatment).

Clinical equivalence of the primary endpoint was demonstrated by comparing the confidence interval of the risk ratio in ORR between ABP 215 and bevacizumab to a prespecified margin. Response was determined by independent review based on RECIST criteria.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in both men and women in the US and the European Union (EU). In the US, there were an estimated 226,160 new cases and 160,340 deaths due to NSCLC in 2012, and in the EU there were an estimated 265,600 new cases and 236,000 deaths due to NSCLC in 2006. NSCLC arises from the epithelial cells of the lung of the central bronchi to terminal alveoli. The histological type of NSCLC depends on the cells of origin, most commonly squamous cell carcinoma, large cell carcinoma and adenocarcinoma. Cigarette smoking is the primary risk factor for NSCLC, and other risks include exposure to second hand smoke, family history, radon exposure and exposure to air pollution.

For patients with metastatic (Stage IV) NSCLC or recurrent NSCLC following surgery and adjuvant chemotherapy, treatment usually consists of combination chemotherapy with a platinum-based regimen, such as cisplatin and gemcitabine or carboplatin and paclitaxel, in repeated 3-week cycles for up to 6 cycles. For patients without squamous cell histology or a recent history of hemoptysis, addition of the anti-VEGF antibody bevacizumab to this regimen improves ORR and prolongs PFS.

Based on these and other data, bevacizumab has been approved in the US, EU and elsewhere for first-line treatment in patients with advanced or recurrent non-squamous NSCLC in combination with platinum-based chemotherapy.

ABP 215 is being developed as a biosimilar to bevacizumab, which is approved in specific combinations in the US, EU and other regions for the treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC as well as metastatic carcinoma of the colon or rectum; metastatic renal cell carcinoma; and other region-specific indications.