Rolontis Leads Hanmi’s Global Ambitions As ADVANCE Phase III Endpoint Met

Rolontis, a novel, long-acting granulocyte colony-stimulating factor (G-CSF) licensed out to Spectrum Pharmaceuticals, has become Hanmi Pharmaceuticals' first drug developed with its proprietary platform to approach the regulatory filings stage in global markets.

Spectrum Pharmaceuticals Inc. plans to file a BLA of its novel neutropenia drug to the US FDA in the fourth quarter of this year as the first Phase III study of Rolontis (eflapegrastim), ADVANCE, has met its primary endpoint of non-inferiority in duration of severe neutropenia in comparison to pegfilgrastim.

In January 2012, Spectrum entered into a licensing agreement with originator Hanmi Pharmaceutical Co. Ltd., gaining global rights for Rolontis outside South Korea, China, and Japan.

This study evaluated the safety and efficacy of Rolontis in the management of chemotherapy-induced neutropenia in 406 patients with early-stage breast cancer. The incidence of adverse events in this study was similar between the Rolontis and the pegfilgrastim arms. The company also announced that RECOVER, the second Phase III study, has completed enrollment.

After the top-line Phase III results were announced, Biomedtracker raised the drug's likelihood of approval by 2% to 62%, higher than the average approval rate of 60%. It said the results replicated the main Phase II finding of non-inferiority of Rolontis compared to pegfilgrastim in the duration of severe neutropenia among breast cancer patients.

The ADVANCE study was an active-controlled trial that enrolled 406 early-stage breast cancer patients, who received docetaxel and cyclophosphamide chemotherapy every 21 days. Patients were randomized 1:1 to treatment with Rolontis or pegfilgrastim. The primary study endpoint was the duration of severe neutropenia (Absolute Neutrophil Counts [ANC] <0.5×109/L) in Cycle 1 of chemotherapy, based on central laboratory assessment of ANC over the 21-day cycle.

“The ADVANCE study affirms the efficacy and safety of Rolontis that was observed in the Phase II study," said Lee S. Schwartzberg, M.D., FACP professor of medicine and division chief, Hematology Oncology, The University of Tennessee Health Science Center, and executive director, UT/West Cancer Center. “If approved, this drug would be a welcome addition to supportive care treatment options for cancer patients receiving myelosuppressive cytotoxic chemotherapy.”

Although the Rolontis ADVANCE trial met its primary endpoint of non-inferior efficacy to pegfilgrastim and adverse events were reported to be comparable between both study arms, the company did not release more details to allow review of the quantitative efficacy and safety data from the trial, noted Biomedtracker.

"Despite the lack of concrete data presently available, we are increasing our likelihood of approval by 2% due to the modestly positive results reported overall," Biomedtracker said. "It should be noted that four biosimilars to pegfilgrastim are in various phases of development and may impact the commercial launch of Rolontis, should it be approved."

Pegfilgrastim Biosimilar Progress

No biosimilar versions of the originator drug, Neulasta, which is used to treat chemotherapy-induced neutropenia, have yet been approved in the EU or gained a recommendation from the CHMP. (Also see "First Biosimilar Neulasta In Final Stages Of EMA Review Process" - Pink Sheet, 15 Dec, 2017.)

Pegfilgrastim biosimilar products that are under review by the EMA include Coherus BioSciences Inc.'s CHS-1701, which was filed with the EMA at the end of November 2016. The drug is also under review in the US, although it received a complete response letter from the FDA in June.

Other pegfilgrastim products under evaluation by the CHMP include Cinfa Biotech's B12019, which was accepted for review in early October 2017. Also that month, Sandoz Inc. announced that its re-filing for Zioxtenzo had been accepted; the company had withdrawn its earlier filing in January 2017 because of manufacturing concerns and blood concentration study results.

On Dec. 1, Mylan/Biocon Ltd. announced that their re-filing for MYL-1401H had been accepted. The original submission (July 2016) was withdrawn on August 15, 2017 because of a manufacturing facility re-inspection.

Hanmi's Global Progress, Pipeline

Hanmi is also making advances in other late phase pipelines licensed out to global partners.

Interim Phase II clinical study data for Hanmi and Spectrum's novel, oral pan-HER inhibitor poziotinib announced in October last year showed evidence of significant antitumor activity, with an overall response rate of 73%, in non-small cell lung cancer patients with EGFR (epidermal growth factor receptor) exon 20 insertion mutations. (Also see "Poziotinib Shows Promise In EGFR Exon 20 Mutant NSCLC" - Scrip, 19 Oct, 2017.)

Hanmi's efpeglenatide, which has been licensed out to Sanofi, is set to enter various Phase III trials, including a combination therapy with metformin and a combination therapy with basal insulin. Based on the Phase III results, Sanofi is aiming to file for BLA to the FDA in 2021.

Following a series of mega licensing deals in 2015 and 2016, Hanmi is focusing on developing novel drugs for obesity and diabetes, NASH, oncology and rare diseases.

At present, it is progressing 25 novel molecules including seven for obesity and diabetes (including biologics), 12 anti-cancers, one for immune disorders, and three for rare diseases.

Hanmi has already filed for a Phase I study of a LAPS Tri-agonist (HM15211), a therapeutic option for the treatment of NASH (non-alcoholic steatohepatitis) that has shown good efficacy in improvement of liver inflammation and fatty liver in animal models.

Its acute myeloid leukemia, the FLT3 inhibitor (HM43239) has effectively inhibited FLT3 mutations in a preclinical trial and is also said to inhibit leukemia stem cells, which are seen as one of the major reasons of recurrence.

From the editors of PharmAsia News.

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