Amgen Acquires Five Prime for its Oncology Pipeline

Zev A. Wainberg, MD

Amgen has completed its planned acquisition of Five Prime Therapeutics for $38.00 per share in cash, or approximately $1.9 billion.¹ Five Prime's lead candidate is bemarituzumab, a first-in-class therapy that targets FGFR2b, which is overexpressed in approximately 30% of patients with HER2-negative gastric cancer, as well as in other solid tumors.²

Additionally, the FDA has granted bemarituzumab breakthrough therapy designation for patients with gastric or gastroesophageal junction (GEJ) cancer.³

“Five Prime fits squarely within Amgen's leading oncology portfolio and includes bemarituzumab, a phase 3 trial-ready, first-in-class program for gastric cancer, the third leading cause of cancer mortality worldwide,” Robert A. Bradway, chairman and chief executive officer at Amgen said in a press release. “Working with the dedicated professionals joining us from Five Prime, we plan to quickly move bemarituzumab into a phase 3 study, bringing it one step closer to helping patients suffering from gastric cancer.”

Amgen officials said they will continue to review additional Five Prime oncology agents.

Bemarituzumab is designed to block fibroblast growth factors (FGFs) from binding and activating FGFR2b, inhibiting several downstream pro-tumor signaling pathways. Results from the phase 2 FIGHT trial (NCT03694522) showed positive results in patients with previously untreated advanced gastric or GEJ cancer who were HER2 negative. This is the first trial to evaluate targeting overexpression of FGFR2b.

Bemarituzumab, added to a modified fluoropyrimidine, leucovorin, and oxaliplatin (FOLFOX6) chemotherapy regimen, led to clinically meaningful and statistically significant improvements in progression-free and overall survival (OS) in the frontline setting of gastric or GEJ cancer, according to results presented during the virtual 2021 Gastrointestinal Cancers Symposium.⁴

“The FIGHT trial is the first study to evaluate targeting the overexpression of FGFR2b in any cancer and is the first randomized data set of any fibroblast growth factor receptor inhibitor in any malignancy,” said lead FIGHT study author Zev A. Wainberg, MD, during his presentation of the data. Wainberg is professor of medicine at UCLA and co-director of the UCLA GI Oncology Program in Santa Monica, California.

At the data cutoff of May 2020, median PFS, which was the primary end point of the study, for patients treated with bemarituzumab/mFOLFOX6 (n = 77) was 9.5 months (95% CI, 7.3-12.9). In the placebo/mFOLFOX6 arm (n = 78), PFS was 7.4 months (95% CI, 5.8-8.4), leading to a 32% reduction in the risk of disease progression or death with bemarituzumab (HR, 0.68; 95% CI, 0.44-1.04; P = .0727).

Median OS in the bemarituzumab arm was not reached at the data cutoff (95% CI, 13.8–not reached) compared with 12.9 months (95% CI, 9.1-15.0) for the placebo/mFOLFOX6 arm (HR, 0.58; 95% CI, 0.35-0.95; P = .0268). PFS and OS increased with higher levels of FGFR2b overexpression, investigators found.

Treatment related adverse events of grade 3 or higher occurred in 63 patients (82.9%) in the bemarituzumab arm and 57 patients (74%) in the placebo arm. Five patients died on bemarituzumab and 4 patients died on the placebo arm. Additionally, bemarituzumab was associated with an increase in corneal adverse events and stomatitis, the majority of which were reversible.

Amgen officials said they company plans to evaluate bemarituzumab in other cancers that overexpress FGFR2b.

The acquisition also supports Amgen's international expansion strategy. Gastric cancer is particularly prevalent in the Asia-Pacific region, where Amgen expects to generate significant volume growth in the coming years. Amgen plans to leverage its presence in Japan and other Asia-Pacific markets to maximize bemarituzumab’s potential evaluating the potential for bemarituzumab in other cancers that overexpress FGFR2b.

Another agent in Five Prime’s pipeline is FPT155, a novel checkpoint inhibitor. This is being tested in the phase 1, open-label FPT155-001 (NCT04074759) trial, which is enrolling 322 patients with advanced solid tumors.

References

1. Amgen successfully completes acquisition of Five Prime Therapeutics. News release. Amgen. April 16, 2021. Accessed April 19, 2021. https://www.amgen.com/newsroom/press-releases/2021/04/amgen-successfully-completes-acquisition-of-five-prime-therapeutics
2. Amgen to acquire Five Prime Therapeutics for $1.9 billion in cash. News release. Amgen. March 4, 2021. Accessed April 19, 2021. https://www.amgen.com/newsroom/press-releases/2021/03/amgen-to-acquire-five-prime-therapeutics-for-$1-9-billion-in-cash
3. Amgen’s investigation targeted treatment bemarituzumab granted breakthrough therapy designation. News release. Amgen. April 19, 2021. Accessed April 19, 2021. https://prnmedia.prnewswire.com/news-releases/amgens-investigational-targeted-treatment-bemarituzumab-granted-breakthrough-therapy-designation-301271859.html
4. Wainberg ZA, Enzinger P, Kang YK, et al. A double-blind randomized study of bemarituzumab (bema) plus mFOLFOX6 versus placebo plus mFOLFOX6 as a first-line treatment for gastric/gastroesophageal junction cancer (FIGHT). Presented at American Society of Clinical Oncology Gastrointestinal Cancer Symposium. https://www.fiveprime.com/file.cfm/16/docs/Bema%20P2%20FIGHT%20Results%20ASCO%20GI%20011521.pdf