Mylan NV Monday accomplished what others have failed to do – get FDA approval for a Neulasta biosimilar.

The licensing of Fulphila (pegfilgrastim-jmbd), co-developed with Biocon Ltd., of Bangalore, India, also scores a first for the FDA, which has been playing catch-up with the EMA’s head start on the biosimilar path. Although the EMA has authorized 43 biosimilars since 2006, it has yet to approve a biosimilar to Amgen Inc.’s Neulasta, which is used to treat neutropenia in patients on chemotherapy in certain types of cancer.

In another first, the FDA didn’t hold an advisory committee meeting on Fulphila, even though it was the first biosimilar referencing Neulasta. The agency generally convenes an advisory committee for the first proposed biosimilar to a given reference biologic, especially if there are novel scientific or regulatory questions that need to be discussed.

“The FDA did not hold an advisory committee meeting for this product, because we determined that the application did not raise issues that needed discussion,” FDA spokesman Jeremy Kahn told BioWorld.

While Fulphila can claim several firsts, it is not the first pegfilgrastim biosimilar approved in a regulated market. Apobiologix, a division of Toronto-based Apotex Inc., claimed that honor last week when Health Canada approved its Lapelga.

Apotex was the first in line to snag FDA approval for a pegfilgrastim biosimilar, with the agency accepting its application in December 2014. But whatever happened with the application remains between the agency and the privately held company, as Apotex has been mum on the subject.

Getting approval for a biosimilar to Amgen’s long-acting G-CSF drug hasn’t been an easy task for anyone. After greenlighting Sandoz Inc.’s Zarxio (filgrastim) as the first U.S. biosimilar in 2015, the FDA accepted Sandoz’s application for a Neulasta biosimilar later that year, but then handed the company a complete response letter (CRL). Coherus Biosciences Inc.’s candidate, submitted in 2016, met the same fate last year.

Several months after accepting Mylan’s biosimilar application in February 2017, the FDA gave the Hertfordshire, U.K., company a CRL relating to a pending update of chemistry, manufacturing and controls data following modifications made to the facility that would be used to manufacture the biosimilar. At the time, Biocon said the letter was not expected to affect commercial launch timing in the U.S., which Mylan had predicted would occur late this year or early next year. (See BioWorld Today, Oct. 11, 2017.)

Launch plans

That optimism proved true, as Mylan said it is preparing to launch Fulphila in the “coming weeks,” bringing the first U.S. competition to Neulasta, which produced nearly $4.7 billion in global sales last year, according to Cortellis.

It will be an at-risk launch, since Mylan is in a patent dance with Thousand Oaks, Calif.-based Amgen over two patents claiming methods of purifying proteins used in manufacturing biologics. In keeping with the Biologic Price Competition and Innovation Act, the companies are scheduled to conduct fact and expert discovery through 2019 with a trial expected around midyear, Leerink Partners LLC analyst Geoffrey Porges said. However, he noted, Mylan and Amgen are trying to resolve the litigation through court-sponsored mediation.

Regardless of whether there’s a trial or a settlement, Porges said he views the “manufacturing patents as weak protection for Amgen, and we are not surprised to see Mylan launch at risk against them.”

Besides being the first Neulasta biosimilar approved in the U.S., Fulphila would be one of only a handful of biosimilars to launch in the country. Some of those biosimilars have found it difficult to gain quick traction against a long-established innovator. But Fulphila could benefit from a reimbursement change in the 340B drug discount program, which accounts for about 30 percent of Neulasta’s U.S. sales.

Potential 340B benefit

Under the revisions the Centers for Medicare and Medicaid Services made to 340B reimbursement this year, biosimilars qualify as a “new and innovative technology” that are reimbursed at average sales price (ASP) plus 6 percent for two to three years, while the innovator will be reimbursed at ASP minus 22.5 percent.

“This is a key financial incentive for rapid uptake for the biosimilar in 340B-participating hospitals,” Leerink Partners LLC analyst Ami Fadia said.

That incentive could work against Fulphila in the long term, though. Once its two- to three-year window as a new and innovative technology closes, it will be reimbursed like the innovator. And like the innovator, it will have to compete with newer biosimilars that are still in their favorable 340B reimbursement period, Fadia said.

Even in the near-term, the 340B incentive could be offset somewhat by Amgen’s Neulasta Onpro, which represents about 62 percent of U.S. Neulasta sales, said Salim Syed, a Mizuho Securities USA LLC analyst. “While it’s not clear if this 62 percent is equally spread across channels, Amgen has previously communicated that many of the large 340B institutions have switched to the Onpro system,” he added.

The competition

Part of Amgen’s strategy to prepare for Neulasta biosimilar competition was to convert at least half of the treated population to Neulasta Onpro, a next-generation medical device combo product that’s more convenient for patients as it eliminates a return visit to the provider for an injection the day after chemo. That strategy “could prove sticky for some physicians and centers and lessen the degree of revenue erosion compared to historical precedents,” Porges said.

Jefferies LLC analyst Michael Yee said Amgen has “swapped around 60 percent of utilization to the more simple Onpro device.” He expected that the other 40 percent of Neulasta sales could decline by 10 percent due to market share loss or price erosion, if Mylan prices Fulphila at a 20 percent to 25 percent discount. Mylan has yet to provide pricing guidance; some of the first biosimilars to launch in the U.S. offered only a 15 percent discount off the list price.

Meanwhile, Amgen likely is working closely with many big customers and locking in contracts to ensure a consistent supply and reliability of product, Yee said, adding that it takes time for many hospitals and big customers to change formularies.

The Neulasta market could get more competitive in November if Coherus’ biosimilar is approved on its PDUFA date. Other biosimilars, from Sandoz and Amneal Pharmaceuticals Inc./Adello Biologics LLC, could come to market in two to three years – just as Fulphila loses its 340B reimbursement advantage.

Fulphila is the second biosimilar from the Mylan/Biocon team. In December, the FDA approved the partners’ Ogivri, a biosimilar to Roche Holding AG’s breast cancer therapy, Herceptin (trastuzumab). Under the partnership, Mylan has exclusive commercialization rights for Fulphila in the U.S., Canada, Japan, Australia, New Zealand and in the European Union and European Free Trade Association countries. Biocon has co-exclusive commercialization rights in the rest of the world. (See BioWorld, Dec. 4, 2017.)

In addition to the good news about Fulphila, Mylan and Biocon had a bit of déjà vu when they recently received a CRL on their Lantus (insulin glargine, Sanofi SA) follow-on, which is being developed as a 505(b)(2) drug in the U.S. The letter was expected, as the companies already had agreed to provide the agency with additional clinical data in support of a manufacturing site change from Bangalore to Malaysia, Julie Knell, senior director for Mylan’s global product communications, told BioWorld.

“Together, Mylan and Biocon are already executing on all required activities we had agreed upon with FDA,” Knell said, adding that the partners don’t anticipate any impact to the timing of the product’s approval and launch.

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