BASEL, Switzerland—Last week, Sept. 3 to be precise, Novartis announced that Zarxio (filgrastim-sndz) was now available in the United States through its subsidiary Sandoz, noting that this makes Zarxio first biosimilar approved by the U.S. Food and Drug Administration (FDA) and the first to launch in the United States.
Not that the process was without its hurdles. Though the biosimilar (a generic version of a biological therapeutic/biologic) was approved by the FDA on March 6, Amgen took issue with it. This isn’t surprising, as Zarxio is the generic version of Amgen’s highly successful biologic Neupogen. Both Neupogen and Zarzio are aimed at treating neutropenia, which occuts when the white blood cells known as neutrophils drop below healthy levels because of such things as cancer treatment or HIV/AIDS.
There had been some wrangling in the court as to this Neupogen “copycat,” particularly during the summer as the case was argued, as Amgen sought to block sales of the drug over differing interpretations of the Biologics Price Competition and Innovation Act, which is the basis for biosimilar development and approval, as well as other legislation and legal precedents. In fact, much of the legal confusion and arguments arises because the new law has no real case precedent, while the roughly three-decades-old law that had guided how generic drugs have been handled has a great deal of precedent decisions, and potentially conflicts with the new law in some regards.
Per the biosimilars pathway established by the Biologics Price Competition and Innovation Act, data on Zarxio showed “no clinically meaningful differences to the U.S.-licensed reference product,” according to Novartis and Sandoz. During the head-to-head PIONEER study between Zarxio and Neupogen, both products reportedly produced the expected reduction in the duration of severe neutropenia in cancer patients undergoing myelosuppressive chemotherapy (1.17 and 1.20 days for Zarxio and the reference product, respectively). The mean time to absolute neutrophil count recovery in cycle 1 was also similar (1.8 days ± 0.97 in ZARXIO arm vs 1.7 days ± 0.81 in reference product arm). No immunogenicity or antibodies against rhG-CSF were detected throughout the study, Novartis reported.
Amgen sought to protect its sales by blocking U.S. sales of Zarxio, which Sandoz is offering at a price of about 15 percent less than Neupogen. In July, a U.S. appeals court ruled that Novartis had to wait until Sept. 2 to launch Zarxio. Amgen stock prices were down about 1.5 percent on Sept. 3, following the news of Zarxio’s launch.
“As the pioneer and global leader in biosimilars, Sandoz has maintained a commitment to bringing high-quality biosimilar medicines to patients and healthcare professionals around the world,” said Richard Francis, global head of Sandoz. “With the launch of Zarxio, we look forward to increasing patient, prescriber and payer access to filgrastim in the U.S. by offering a high-quality, more affordable version of this important oncology medicine.”
“While biologics have had a significant impact on how diseases are treated, their cost and co-pays are difficult for many patients and the healthcare budget in general. Biosimilars can help to fill an unmet need by providing expanded options, greater affordability and increased patient access to life-saving therapies,” said Dr. Ralph Boccia, medical director of the Center for Cancer and Blood Disorders, and chief medical officer for the International Oncology Network (ION), in the Novartis news release about Zarxio’s launch.
While this may sound acrimonious, the legal challenges weren’t unexpected given that we see plenty of challenges with traditional generic drugs. And the two companies are actually working together in other areas.
In fact, just a couple days before the Zarxio announcement, Novartis announced it had entered into a global collaboration with Amgen to commercialize and develop pioneering neuroscience treatments. The companies will partner in the development and commercialization of a BACE inhibitor program in Alzheimer’s disease (AD). Novartis’ oral therapy CNP520 will be the lead molecule and further compounds from both company’s preclinical BACE inhibitor programs may be considered as follow-on molecules. The collaboration will also focus on new Amgen drugs in the migraine field, including Phase 3 AMG 334 and Phase 1 AMG 301. For the migraine program, Novartis will have global co-development rights and commercial rights outside the United States, Canada and Japan.
“This Novartis collaboration with Amgen highlights our clear commitment to neuroscience and to bring multiple, new targeted therapies to patients living with Alzheimer’s disease and migraine, where the unmet medical need remains high.” said David Epstein, head of Novartis Pharmaceuticals.
Alzheimer’s disease is an irreversible, progressive brain disease characterized by loss of memory and other cognitive abilities. Amyloid build-up is considered a key driver of the progressive damage of the nervous system in AD. CNP520 is an oral drug designed to prevent the production of different forms of amyloid and has the potential to prevent, slow or delay the symptoms associated with AD. It is currently in phase 1/2a trials. CNP520 is planned to be included in a pioneering prevention study in people with a genetic risk of developing AD, in collaboration with the Banner Alzheimer’s Institute.
Migraine is a severe headache condition affecting more than 10 percent of the population worldwide and a leading cause of disability. AMG 334 is a fully human monoclonal antibody under investigation for the prevention of migraine. AMG 334 inhibits the activity of calcitonin-gene-related-peptide (CGRP) by targeting its receptor. CGRP is believed to play a key role in the development of migraine. AMG 334 is currently under evaluation in several large global, randomized, double-blind, placebo-controlled Phase 3 trials to assess its safety and efficacy in migraine prevention. In addition to AMG 334, the migraine portfolio will include the development of AMG 301 and potentially another investigational compound of Amgen. AMG 301 is a monoclonal antibody being investigated in Phase 1 trials for the prevention of migraine.
The partnership with Amgen follows two recent developments in the Novartis neuroscience portfolio aimed at complementing Novartis’ neuroscience presence and pipeline in, among others, multiple sclerosis, AD and neuromuscular diseases. In July, Novartis acquired Spinifex Pharmaceuticals, adding Phase 2 compound EMA401 for the treatment of neuropathic pain to the portfolio. In August, Novartis announced that it has entered into an agreement to acquire all remaining rights to ofatumumab from GlaxoSmithKline plc for relapsing-remitting multiple sclerosis and certain other autoimmune indications.
Under the terms of the Novartis and Amgen arrangement, the companies will share responsibilities for development and commercialization of the BACE inhibitor program. Amgen will pay an upfront payment and milestone payments as well as disproportional research and development costs for an agreed upon period followed by a 50/50 cost and profit share arrangement. For the compounds in the migraine field, Novartis receives global co-development rights and commercial rights outside the United States, Canada and Japan to the investigative molecules in Amgen’s migraine portfolio. This includes AMG 334 in Phase 3 and AMG 301 in Phase 1 as well as an option to commercialize an additional early-stage Amgen molecule in these territories. Novartis will fund disproportional global research and development expenses for an agreed period on the migraine programs and will pay Amgen double-digit royalties on sales.