It might not add much to Pfizer Inc.'s bottom line, since oral Ibrance (palbociclib) is approved already as a first-line therapy, but the first randomized phase III data with the compound made a strong showing in the trial called PALOMA-3, stopped early because of solid efficacy.
A data monitoring committee recommended that New York-based Pfizer end the study, since the primary endpoint of progression-free survival (PFS) was met. Ibrance was combined with the estrogen receptor antagonist fulvestrant (Faslodex, Astrazeneca plc) vs. fulvestrant plus placebo in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer following the advance of the disease during or after endocrine therapy.
Ibrance, a cyclin-dependent kinase (CDK) 4/6 inhibitor, won the go-ahead from U.S. regulators in February for use in combination with Femara (letrozole, Novartis AG), having earlier wowed the American Association for Cancer Research meeting in San Diego with data from the phase II PALOMA-1 trial showing that Ibrance doubled PFS in women with metastatic estrogen receptor-positive (ER-positive) breast cancer when added to standard treatment with Femara, an estrogen synthesis inhibitor. The AACR data came almost simultaneously with the award of breakthrough therapy designation. (See BioWorld Today, April 8, 2014, and Feb. 4, 2015.)
"We don't expect the results of PALOMA-3 to add a lot to Ibrance peak sales by itself – we believe most patients will elect to instead take Ibrance first-line rather than second-line – but this trial should in the short-term only add to what already appears a strong early launch by adding second-line patients [and facilitating payers' reimbursement of second-line patients]," wrote Evercore ISI analyst Mark Schoenebaum in an alert to investors, adding that the latest trial "only adds to our probability of success for the phase III PALOMA-2 trial, confirming the benefit of Ibrance plus Femara in first-line patients and supporting full approval." The primary endpoint of that experiment is PFS, and the trial is event-driven but could read out late this year.
Pfizer's stock (NYSE:PFE) closed Wednesday at $35.21, up 18 cents.
Jefferies analyst Jeffrey Holford reported from a meeting with a breast-cancer doctor that Ibrance's benign toxicity profile "has been an important driver behind the strong initial launch. Even our expert, who was 'shocked' that the FDA approved Ibrance on phase II data alone, has been widely prescribing Ibrance across multiple lines in the hormonal metastatic setting, and noted that Ibrance is being rapidly and broadly adopted by oncologists," Holford wrote in a research report, adding that the doctor found "limited push-back by payers when using Ibrance across the different lines of hormonal metastatic treatment."
The drug's mechanism of action is under investigation by others in the cancer space. In February, G1 Therapeutics Inc. hauled down $33 million in series B money to advance G1T28 as an oral antineoplastic agent and as an intravenous (I.V.) bone marrow chemoprotectant. Candidates taking aim at CDK4/6 are in the works by Novartis AG, of Basel, Switzerland, and Indianapolis-based Eli Lilly and Co. The I.V. factor and experience in bone marrow could give G1 an edge in the class; G1T28 is designed to pause division of cells in the marrow while chemotherapy is on board, but not for longer. (See BioWorld Today, Feb. 6, 2015.)
Tolero Pharmaceuticals Inc., of Salt Lake City, has alvocidib, a CDK inhibitor with selective activity against CDK9 and also CDK4/6. The compound has shown clinical activity in multiple types of cancer including both solid tumors and hematological malignancies. The firm's primary focus is acute myeloid leukemia (AML), against which the drug has been tested in phase II trials involving more than 400 patients. The most significant activity has been seen when alvocidib is combined in a sequential dosing regimen that includes the standard-of-care agents cytarabine and mitoxantrone. Based on data from a total of eight phase II trials in front-line as well as relapsed/refractory AML, alvocidib will be evaluated in a pivotal phase III study to support regulatory filing and approval for this indication. (See BioWorld Today, Aug. 11, 2014.)
Berkeley Heights, N.J.-based Cyclacel Pharmaceuticals Inc. has oral seliciclib (CYC202), said to block CDK2, CDK7 and CDK9. In late 2010, the firm reported top-line data from its phase IIb APPRAISE trial in non-small-cell lung cancer showing no difference between the seliciclib and placebo arms in terms of median PFS (48 days vs. 53 days, respectively), though results turned up an increase in median overall survival favoring the seliciclib arm (388 days vs. 218 days, respectively). APPRAISE enrolled 187 patients whose disease had progressed on at least two prior therapeutic regimens. In early March, the firm raised $10 million, some funds of which were earmarked to advance phase I trials of its second-generation CDK inhibitor known as CYC065.
Cortellis Clinical Trials Intelligence lists 738 experiments testing CKD inhibitors, mostly early stage. Of these, 31 are phase III, with 15 completed and 16 still recruiting.