Sentinel For Biosimilars? Biologics Post-Market Monitoring Is Focus Of New Consortium

Group of sponsors, insurers and health systems will draw on datasets of de-identified pharmacy and medical claims data to monitor effectiveness and safety of novel biologics and their corresponding biosimilars.

A new multi-stakeholder consortium will leverage the infrastructure created for FDA's Sentinel Initiative to conduct active post-marketing surveillance of biosimilars and their reference products in the US.

The Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) is a non-profit, public service initiative that will draw on large datasets of de-identified pharmacy and medical claims data to monitor the effectiveness and safety of novel biologics, their corresponding biosimilars and other related products.

The initiative is aimed at addressing expected uncertainties in the minds of prescribers, patients and others about the safety and effectiveness of biosimilars licensed under the 351(k) regulatory pathway relative to their corresponding reference products.

"We expect that as biosimilars come to the market … physicians, patients and other stakeholders will have questions about the safety and effectiveness of these products," BBCIC's Eichelberger said.

"Similar to the US experience with the introduction of generics, we expect that as biosimilars come to the market physicians, patients and other stakeholders will have questions about the safety and effectiveness of these products," BBCIC Program Director Bernadette Eichelberger said.

Eichelberger discussed the initiative during the open public hearing of FDA's Arthritis Advisory Committee review of Celltrion Inc.'s CT-P13, a proposed biosimilar to Janssen Biotech Inc.'s Remicade (infliximab), on Feb. 9.

"Currently in the US we do not have an active post-approval process that is built for purpose to monitor biosimilars and biologics," Eichelberger said, adding that the BBCIC will fill this void with a science-driven, transparent approach that leverages existing distributed research network resources.

Contracting practices are also being eyed as a potential answer for marketplace uncertainties about biosimilars (see sidebar).

Partners And Governance

BBCIC was established by the Academy of Managed Care Pharmacy, but it is a separate entity with its own distinct budget and governing structure.

The initiative is in keeping with AMCP's view that post-approval pharmacovigilance of biosimilars and their reference products in the US can be accomplished through existing mechanisms and is not dependent upon distinguishable nonproprietary names, as proposed by FDA in an August draft guidance (Also see "FDA Biosimilar Naming Proposal Pits Providers, Patients Against Insurers, Pharmacies" - Pink Sheet, 16 Nov, 2015.).

BBCIC is a collaboration of managed care organizations, integrated delivery systems, pharmacy benefit managers, research institutions and pharmaceutical companies that are providing either financial or in-kind support (see box).

A planning board responsible for the group's charter, operational policies and procedures, and research plans includes BBCIC staff, representatives from all the participating organizations, and up to three public representatives from patient, consumer and physician advocacy organizations.

On Feb. 19, BBCIC's board of managing directors approved the appointment of two of these public members: Robert Miller, American Society of Clinical Oncology VP-quality and guidelines, and medical director of CancerLinQ; and Eleanor Perfetto, senior VP-strategic initiatives for the National Health Council.

BBCIC Participating Organizations

• AbbVie
• Amgen
• Anthem-HealthCore
• Boehringer Ingelheim
• Express Scripts, Inc.
• Group Health Cooperative
• Harvard Pilgrim Health Care
• HealthPartners
• Henry Ford Health System
• Merck
• Momenta
• Pfizer

Standing On Sentinel's Shoulders

BBCIC will apply the same scientific, analytical methods that are used in FDA's Sentinel Initiative, a post-market surveillance network that has access to claims and other data for more than 190 million individuals.

Although Sentinel was built for purposes of conducting safety surveillance of marketed drugs, FDA recently said it is looking at ways to use the electronic data network to monitor drug effectiveness post-approval (Also see "FDA Aims To Tap Sentinel Data Network For Drug Effectiveness Studies" - Pink Sheet, 8 Feb, 2016.).

In an interview, Eichelberger noted that BBCIC includes several of the data partners involved in Sentinel and uses the same coordinating center.

"The way to think of the BBCIC is we're standing on the shoulders of Sentinel," Eichelberg said, noting that BBCIC will leverage the development work, research design, capability and framework built for the FDA initiative.

Although BBCIC has not yet established a liaison with FDA, Eichelberger said she does not believe the agency will view the consortium as duplicating the work done through Sentinel, in part because Sentinel was built with the expectation that ultimately it would become more of a public utility rather than simply an FDA tool.

In response to questions from "The Pink Sheet," FDA said it is not coordinating its post-marketing monitoring activities with BBCIC. "However, FDA has stated that it believes that the infrastructure underlying the Sentinel system should not be created for the exclusive use of just one agency, but rather it should be developed in such a way that it can become a national resource."

Research Plans

BBCIC plans to conduct a range of analyses, including population characterization, epidemiologic studies, and active observational sequential analysis of biologics and biosimilars.

In the category of population characterization, the group's research activities are expected to include evaluations of disease prevalence, product exposure and utilization, and characterization of subpopulations or cohorts.

Safety assessments may include examination of adverse event frequency, clinical loss of efficacy over time and comparisons of acute reactions across products. Effectiveness assessments may include a focus on clinical or measurable endpoints, real-world dosing, compliance and gaps in therapy.

BBCIC research plans and protocols will be posted on the group's website, and research reports will be submitted for publication within six months after completion.

The 2016 research plan is still in development but is expected to include groundwork for studies of biosimilars and innovator products by assessing how they are used and coded. This includes descriptive analyses starting with the innovator product on data availability, treatment patterns, medical coding practices and cohorts.

Biological product categories for which biosimilars are projected to be available in the next three years will be the initial research focus. These include tumor necrosis factor inhibitors and epoetin alfa.

Celltrion's CT-P13 appears well positioned for near-term approval as the first biosimilar of a TNF inhibitor following a strong advisory committee recommendation in favor of licensing for all available indications on the Remicade label (Also see "Celltrion's Biosimilar Gets FDA Panel Nod Despite Extrapolation Concerns" - Pink Sheet, 9 Feb, 2016.).

BBCIC also expects to initiate safety and effectiveness research on granulocyte colony-stimulating factor agents in 2016. This includes Sandoz Inc.'s biosimilar Zarxio (filgrastim-sndz) and its reference product, Amgen Inc.'s Neupogen (filgrastim), as well as Amgen's second-generation agent Neulasta (pegfilgrastim) and Teva Pharmaceutical Industries Ltd.'s Granix (tbo-filgrastim).

Apotex Inc. also is seeking approval of a Neupogen biosimilar, and both Apotex and Sandoz have submitted 351(k) applications referencing Neulasta (Also see "Pending Biosimilars" - Pink Sheet, 2 Nov, 2015.).