With the detailing at a scientific conference by Spectrum Pharmaceuticals Inc. of phase III data with Rolontis (eflapegrastim), a long-acting granulocyte colony-stimulating factor (GCSF) for chemotherapy-induced neutropenia, attention turned to the prospects of such good news translating to the product's label.
Chief Operating Officer Thomas Riga said during a conference call with investors that "our full intention is to have in the label a noninferiority indication to pegfilgrastim [Neulasta, Amgen Inc.]," but "the data [are] the data," and regulators will make the final decision.
Meanwhile, Henderson, Nev.-based Spectrum said that, in the experiment called Advance, Rolontis turned up an absolute risk reduction (ARR) of severe neutropenia of 8.5 percent (95 percent CI: 0.2 percent, 16.2 percent) vs. pegfilgrastim in cycle one. ARR was defined as the difference in percentage of the patients experiencing no severe neutropenia (Rolontis 84.2 percent; pegfilgrastim 75.7 percent). New safety data showed that adverse events (AEs) were not significantly different between the two treatment arms.
The company offered the findings at the Multinational Association of Supportive Care in Cancer annual meeting in Vienna. Spectrum also said the phase III trial called Recover met its primary efficacy endpoint of noninferiority in duration of severe neutropenia (DSN) between Rolontis and pegfilgrastim. In February, the firm reported that Advance met its primary efficacy endpoint of noninferiority in DSN compared to pegfilgrastim.
"Rolontis continues to fly below the radar," Jefferies analyst Matthew Andrews pointed out in a research report last month, as Spectrum-watchers tend to focus more on poziotinib (pozi), an oral, quinazoline-based pan-HER inhibitor in the works at the phase II stage for cancer. Understandably so, in the view of H.C. Wainwright's Edward White, who said recent pozi data in non-small-cell lung cancer (NSCLC) with exon 20 patients "appears remarkable." The drug is an oral, irreversible, tyrosine kinase inhibitor (TKI) under investigation in NSCLC with a genetic mutation exon 20 insertion in EGFR or HER2, as well as in breast cancer patients.
At Wainwright's April health care conference in Monaco, Spectrum provided an update from the pozi phase II study at MD Anderson Cancer Center, which included an overall response rate of 64 percent in the first 11 EGFR, exon 20-mutant NSCLC patients. After a follow-up of 6.6 months, the median progression-free survival had not been reached. The most common AEs observed in the study included skin rashes and diarrhea, both of which are previously observed EGFR inhibitor-related toxicities. The next check-in on pozi is expected in the second half of this year at the World Conference on Lung Cancer in Toronto.
At the American Society of Clinical Oncology meeting in June, Takeda Pharmaceutical Co. Ltd., of Osaka, Japan, presented during the poster session findings with TAK-788, a small-molecule TKI targeting EGFR and HER2 mutations, including exon 20 insertions. The company talked about the safety, pharmacokinetics and preliminary antitumor activity of the molecule in NSCLC patients, and Andrews watched with interest. A physician discussant "did a side-by-side comparison of TAK-788 and pozi," he said. Based on the preclinical data in the poster, "it appears Takeda has little if any room to push the dose higher. Data in HER2 are small, and it is unclear if this will translate into a potential addressable population," along with whether the compound is a potential threat to pozi.
Eyeing strategy on price
Last week, Rolontis shared some of pozi's limelight. The Advance study is a multicenter, randomized, active-controlled trial that enrolled 406 early stage breast cancer patients, who received docetaxel and cyclophosphamide chemo every 21 days for four cycles. Patients were randomized 1-to-1 to treatment with Rolontis or pegfilgrastim (eflapegrastim n=196; pegfilgrastim n=210). The primary study endpoint was the DSN (absolute neutrophil counts [ANC] <0.5×109/L) in cycle one of chemo, based on central laboratory assessment of ANC over the 21-day cycle. Secondary endpoints included the DSN in cycles two, three and four; time to ANC recovery; depth of ANC nadir; and incidence of febrile neutropenia at cycle one. Patients with stage I to stage IIIa cancer were treated on day one of each of the four cycles with adjuvant/neoadjuvant docetaxel and cyclophosphamide. On day two of each cycle, patients received a single subcutaneous dose of either eflapegrastim 13.2 mg/0.6 mL (equivalent to 3.6 mg GCSF) or pegfilgrastim (6 mg) in a 1-to-1 ratio. The most common AEs, seen in greater than 5 percent of patients, were similar across both treatment groups and included neutropenia, lymphopenia, anemia, leukopenia, febrile neutropenia and bone pain.
The 0.6 mL dosing is important, CEO Joseph Turgeon said during the conference call. Doctors are "not the ones injecting the patients all day with this. The nurses are. And boy, they better be happy with any product that comes out." Spectrum wanted "the same volume, so, the same-size syringe and the same-gauge needle [as standard of care today], because that can mean a different outcome if you have more and more solution to put into the patient, a larger-gauge needle, bigger injection, etc. That was all important to us."
The Recover experiment is a randomized, open-label, active-controlled, multicenter study that enrolled 237 breast cancer patients given docetaxel and cyclophosphamide chemo every 21 days. Patients were randomized in a 1-to-1 ratio to receive either Rolontis (n=118) or pegfilgrastim (n=119). The primary study endpoint was the DSN in cycle one of chemo (ANC <0.5×109/L), based on central laboratory assessment of the counts over a 21-day cycle. Four cycles were evaluated. Secondary endpoints were the same as in the Advance trial, and patients were dosed similarly.
Lee Schwartzberg, lead investigator in the Advance trial, said "there really were no subgroups here that seemed to do better or worse with Rolontis vs. pegfilgrastim, and we looked at weight, and there isn't really any difference either. And of course, both of the drugs, including Rolontis, [are] fixed-dose, and we think that's a convenience for patients. The other thing to keep in mind is that this regimen is right at the border of highly myelosuppressive regimens, and it was picked specifically for that reason. We don't have data, but it's interesting that with the data we saw, one could extrapolate, would expect eflapegrastim to perform at least this well in more highly myelosuppressive regimens. But we haven't tested that formally yet."
Wainwright's White sang the praises of Rolontis as he did with pozi, noting in a report that the former is "a novel agent. Investors may be missing that Rolontis is not fully pegylated, and is therefore a new chemical entity. This means, if approved, Rolontis will not be a biosimilar and will not be tied to the pricing and reimbursement of Neulasta and its biosimilars." Such a scenario "could allow Spectrum the freedom to pursue pricing strategies that are beneficial to the doctors prescribing the drug, or the company could work directly with payers on strategies including rebates and/or discounts," he wrote. "We believe flexible pricing could help Rolontis gain share, especially in the community setting," helped by the company's "seasoned, currently right-sized, commercial sales and marketing team." He said he expects a BLA filing in the fourth quarter of this year, with a European submission early next.
White projected revenue of $650 million in 2025.
Rolontis uses Seoul, South Korea-based Hanmi Pharmaceutical Co. Ltd.'s LAPSCOVERY (Long Acting Protein/Peptide Discovery) platform technology, which prolongs the residence time of a biologic and minimizes the frequency of treatment and dose required, leading to better efficacy and reduced AEs.