FDA Updates

On January 7, 2015, Sandoz, the generics wing of Novartis, announced that the FDA’s Oncologic Drugs Advisory Committee (ODAC) has recommended its biosimilar filgrastim (EP2006) for approval in the United States for use in all indications included in the reference product, Amgen’s Neupogen.¹ This comes within 6 months of Sandoz filing for approval with the FDA under the biosimilar pathway created in the Biologics Price Competition and Innovation Act of 2009. The drug is already marketed globally in 40 countries under the brand name Zarzio.²

Filgrastim, a granulocyte colony—stimulating factor, is used to prevent infection in individuals with a compromised immune system, a common side effect of chemotherapy in cancer patients. Additionally, persons undergoing a bone marrow transplant, those who suffer from chronic neutropenia (low blood neutrophils), or those undergoing leukapheresis are also treated with this biological.³

According to a report in The Pink Sheet, Sandoz had a lot to gain from the global post marketing data on Zarzio, as well as Amgen’s Neupogen. The vast foreign-marketing experience brought in by Sandoz helped convince the ODAC panel—the first FDA panel to review a 351(k) application—of the long-term safety and biosimilarity to Neupogen. Among the evidence included in the filing were results from a phase 1 pharmacokinetics/pharmacodynamics study in healthy volunteers and a phase 3 study that compared the Sandoz product with the approved version of Neupogen in the United States in breast cancer patients on myelosuppressive chemotherapy experiencing severe neutropenia. While the massive patient exposure of the Sandoz product outside of the United States provided assurance of product safety, the article also refers to the vast amount of experience brought to the table by parent company Novartis, which was obvious during the presentation, the article says. The panelists were convinced that EP2006 was highly similar to Neupogen, without any clinically meaningful differences.⁴ The Sandoz application, however, does not guarantee smooth sailing for other companies filing biosimilar applications with the FDA.

References

1. Sandoz biosimilar filgrastim recommended for approval by FDA Oncologic Drugs Advisory Committee [press release]. Holzkirchen, Germany; January 7, 2015. Novartis website. http://www.novartis.com/newsroom/media-releases/en/2015/1885139.shtml.

2. FDA accepts Sandoz application for biosimilar filgrastim [press release]. Holzkirchen, Germany; July 24, 2014. Sandoz website. http://www.sandoz. com/media_center/press_releases_news/ global_news/2014_07_24_FDA_accepts_Sandoz_application_for_biosimilar_filgrastim.shtml.

3. Filgrastim injection. U.S. National Library of Medicine website. http://www.nlm.nih.gov/medlineplus/druginfo/meds/a692033.html. Accessed January 30, 2015. 4. Sutter S. Sandoz makes first biosimilar review look easy; will future sponsors be as lucky? The Pink Sheet. 2015;77(2):4-6.

NIVOLUMAB SHOWS PROMISE IN NSCLC, AFTER RECENT MELANOMA APPROVAL

Nivolumab (Opdivo), a programed death 1 (PD-1) immune checkpoint inhibitor developed by Bristol-Myers Squibb (BMS) and approved for metastatic melanoma, is presenting exciting results in non-small cell lung cancer (NSCLC). Results from CheckMate-017, a randomized, open-label, phase 3 trial, were promising enough for an independent data monitoring committee (DMC) to stop the trial early. The DMC concluded that patients on Opdivo demonstrated superior overall survival (OS) compared with patients in the control arm.¹

The phase 3 study compared Opdivo with docetaxel in previously treated advanced or metastatic squamous cell NSCLC patients. The trial design randomized 272 patients to treatment with 3 mg/kg nivolumab every 2 weeks or docetaxel 75 mg/m2 every 3 weeks, with the primary end point being OS and secondary end points being objective response rate and progression-free survival.¹

In late December 2014, Opdivo received FDA approval for treating patients with advanced melanoma who had advanced after being on ipilimumab.² The approval came 3 months after the first anti-PD-1 agent, Merck’s Keytruda, was approved for the same indication. Meanwhile, Eli Lilly and Company has entered into an agreement with BMS to conduct safety, tolerability, and preliminary efficacy studies of Opdivo in combination with Lilly’s galunisertib (LY2157299). These studies are expected to improve treatment options for patients with advanced glioblastoma, hepatocellular carcinoma, and NSCLC.³ “Our clinical collaboration with Lilly underscores BMS’s continued commitment to explore combination regimens from our immuno-oncology portfolio with other mechanisms of action that may accelerate the development of new treatment options for patients,” said Michael Giordano, senior vice president, head of development, oncology, BMS, in a statement.³

References

1. Checkmate-017, a phase 3 study of Opdivo (nivolumab) compared to docetaxel in patients with second-line squamous cell non-small cell lung cancer, stopped early [press release]. Princeton, NJ: Bristol-Myers Squibb; January 11, 2015. http://news.bms.com/press-release/checkmate-017-phase-3-studyopdivo-nivolumab-compared-docetaxel-patientssecond-line-s.

2. FDA approves Opdivo for advanced melanoma [press release]. Silver Spring, MD: FDA; December 22, 2014. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427716.htm.

3. Bristol-Myers Squibb and Lilly enter clinical collaboration agreement to evaluate Opdivo (nivolumab) in combination with galunisertib in advanced solid tumors [press release]. BMS website. New York, NY, and Indianapolis, IN: Bristol-Myers Squibb; January 13, 2015. http://news.bms.com/press-release/rd-news/bristol-myers-squibb-and-lilly-enter-clinicalcollaboration-agreement-evaluate.

PROVENGE MAY BE BOUGHT BY VALEANT

On January 29, 2015, Dendreon Corporation announced that it had reached an agreement with the Canadian pharmaceutical company Valeant for its troubled prostate cancer vaccine Provenge (sipuleucel-T). Valeant will acquire the worldwide rights for Provenge and some other Dendreon assets for $296 million, subject to higher bids, Dendreon announced in a press release.¹

While hopes for the immunotherapy were high following its approval by the FDA in 2010, the high cost of treatment and reimbursement ambiguity resulted in a sizable slump in drug sales, forcing Dendreon to declare bankruptcy in November 2014.²

EBO

Provenge is an autologous cellular immunotherapy indicated for treating asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer. The complex procedure for manufacturing the drug includes collecting a patient’s immune cells by leukapheresis, exposing the cells to a recombinant human protein (PAP-GM-CSF) for stimulation, and returning them back to the patient.³

References

1. Dendreon reaches agreement for Valeant to serve as “stalking horse bidder” in court supervised sales process [press release]. Seattle, WA: Dendreon; January 29, 2015. Dendreon website. http://files.shareholder.com/downloads/ DNDN/3928332673x0x806226/eece585aaed0-44a7-bbb7-42e0dd81c233/DNDN_News_2015_1_29_General.pdf.

2. Dendreon files for Chapter 11 bankruptcy. Reuters website. http://www.reuters.com/article/2014/11/10/dendreon-bankruptcyidUSL3N0T03GB20141110. Published November 10, 2014. Accessed January 30, 2015.

3. Vaccines, blood and biologics. FDA website. http://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/ucm210037.htm. Accessed January 2, 2015.