Nicholas Saraceno

With Aaron Josephson, director, regulatory policy and intelligence, Teva Pharmaceuticals, serving as the moderator, alongside Stacey Ricci, director, scientific review staff, OTBB, OND, CDER, FDA; Leah Christl, executive director, global biosimilars regulatory affairs & regulatory & R&D policy, Amgen; Marta Wosinka, visiting fellow, The Brookings Institution; and Fabrício Oliveira,head of biologic products and Advanced Therapy Medicinal Products Office, ANVISA, the group convened for a DIA panel discussion, “The Future of Biosimilars and Interchangeable Biologics: Global Development, Harmonization, and the Inflation Reduction Act.”

DIA session, “The Future of Biosimilars and Interchangeable Biologics: Global Development, Harmonization, and the Inflation Reduction Act.” June 28, 2023. DIA 2023, Boston. Image Credit: © Nicholas Saraceno.

The session was intended to identify the regulatory requirements across the globe when it comes to interchangeability—specifically if streamlined development is possible—while keeping the IRA in mind.

Has the industry reached a policy agreement for Phase III style confirmatory studies?

One question that was raised revolved around the cost of developing biosimilars: Has the industry reached a policy agreement for Phase III-style confirmatory studies? Christl noted that there has been quite a bit of progress when it comes to policy, but there are products that do not necessarily need these types of studies. Biosimilars will only evolve in complexity as biologics themselves evolve, so she felt that a blanket statement should not be an option; rather, transparency for biosimilar manufacturers is a must.

In Brazil, noted Oliveira, there have been rumblings of these kinds of studies stopping, and there is an increased flexibility for the South American country when it comes to the Phase III confirmatory studies.

When it comes to interchangeability, should utilizing other countries’ clinical evidence be valid?

In this instance, Oliveira added that it is a decision taken by the patient, and works for that particular market.

Interchangeability designation in the US market

Christl expressed that there is value of interchangeability designation in the US, as it relates to pharmacy substitution. According to Wosinka, the idea of interchangeability has been damaging to biosimilars (referencing a Johnson & Johnson Remicade lawsuit), also pointing out that a substitution of biosimilars in pharmacy is different than generics.

The question was raised as to what regulators are seeing in the market when it comes to regulation. In Brazil, Oliveira shared that there are currently 55 approved biosimilars, with 19 under review and 13 waiting to be reviewed; he recommended that submissions continue with an improvement of guidelines.

Just as the title of the session suggests, Christl suggested that during drug development, global harmonization—with predictability and transparency—be used.

 The Future of Biosimilars and Interchangeable Biologics: Global Development, Harmonization, and the Inflation Reduction Act. June 28, 2023. DIA 2023, Boston.

Articles

Panel explores challenges that could affect their development.

DIA 2023: The Future of Biosimilars, Interchangeables

Led by Graham Cookson, chief executive of UK’s Office of Health Economics OHE), alongside Dimitrios Kourouklis

OHE’s principal economist, Alex Gee, senior director of pricing and access, Parexel International; and Annie Kennedy, chief of policy, advocacy, and patient engagement for the EveryLife Foundation for Rare Diseases, these individuals participated in the DIA panel, “The Inflation Reduction Act Price Setting: What are the Impacts on Biopharmaceutical Innovation from Different Perspectives?”

DIA session, "The Inflation Reduction Act Price Setting: What are the Impacts on Biopharmaceutical Innovation from Different Perspectives?” June 27, 2023. DIA 2023, Boston. Image Credit: © Nicholas Saraceno.

The goal of this panel was to dive into how the Inflation Reduction Act (IRA) affects market conditions, especially when it comes to developers and patient access to treatments.

As Cookson discusses, starting in 2026, the US Department of Health and Human Services (HHS) will be setting Medicare prices for eligible prescription medicines in Part D; this is will be extended to eligible medicines for Part B by 2028. The IRA introduces an inflation rebate to quarterly Part B and annual Part D price increases above inflation; there will also be changes in stakeholder liability for drug costs—there will be a cap to out-of-pocket spending, it smooths cost sharing, and other benefit changes.

So, which drugs are eligible for selection? It includes the top 50 drugs in Part B and Part D respectively (ranked by program expenditures). Single-source drugs, seven or more years after FDA approval and single-source biologics, 11 or more years after approval are also included. On the other hand, drugs with single orphan designation that are only approved for that particular indication, plasma-derived products, “low spend” Medicare drugs (the total Part B and Part D expenditure is less than $200 million annually), and certain “small biotech drugs” up until 2028 would be ineligible.

, IRA mentions two sets of factors that HHS ought to consider for determining the maximum fair price (MFP), including manufacturer-specific data and clinical benefit compared to “therapeutic alternatives.”

As far as the motivation for analyzing the impacts of IRA is concerned, Kourouklis noted that the implications for R&D incentives and innovation are unknown at this point, but are likely to be “far reaching.” However, he made the argument that some of the current estimates of innovation ignore complexities of the law and various consequences, such as reduced market entry and competition in a therapeutic class when an MFP is introduced.

When it comes to its impact on rare diseases, the EveryLife Foundation has been involved with two issues that could affect rare disease therapeutic development:

The creation of two different timelines for small and large molecules that starts negotiated prices following approval: nine years for small and 13 years for large.

An orphan product exemption from negotiation for only drugs approved for single rare diseases.

In the realm of biosimilars, Paraxel’s Gee mentioned that there are two pieces of the IRA that are laid out to lower prices by increasing biosimilar use: a Part B add-on payment and selection delay. Specifically, the add-on payment is increased for those biosimilars that have an average sales price (ASP) that is equal to or below the reference biological prices. And until 2028, eligible biosimilars will become available for the biological reference products’ ASP plus 8%, as opposed to 6%. It must be noted that the add-on payment is temporary, and is intended to not only boost access to biosimilars, but promote competition in the marketplace as well.

 The Inflation Reduction Act Price Setting: What are the Impacts on Biopharmaceutical Innovation from Different Perspectives? June 27, 2023. DIA 2023, Boston.

Session offers a look into the Inflation Reduction Act’s impact on market conditions. 

DIA 2023: The Impact of the IRA

Moderator Nancy Brandish Myers, JD, CEO and founder of Catalyst Healthcare Consulting; Craig Barton, SVP of Policy and Strategic Alliances and executive director, Association for Accessible Medicines; Josie Cooper, executive director, Alliance for Patient Access; and Vinod Mitta, medical officer, Centers for Medicare and Medicaid Services (CMS) Innovation, participated in the panel, “Is Mark Cuban Really Solving the Drug Pricing Problem?” during Day 3 of DIA in Boston.

DIA session, "Is Mark Cuban Really Solving the Drug Pricing Problem?” June 27, 2023. DIA 2023, Boston. Image Credit: © Nicholas Saraceno.

Myers began the conversation to stress how focused the US government is on drug pricing, centered around the launch of the Inflation Reduction Act of 2022 (IRA) last August (with the maximum fair price or MFP, shifting to Medicare Advantage and Prescription Drug plans with an inflation “rebate”), followed by in February 2023, CMS introducing a $2 drug program in which a list of 150 generic drug that address the most common conditions, will be introduced for the aforementioned $2 per month.

This is where Mark Cuban’s Cost Plus Drugs comes in. Essentially, it is an online-only pharmacy that negotiates directly with drug manufacturers, side-stepping pharmacy benefit managers (PBMs) and insurers to offer patients drugs at a lower cost. It offers over 1000 total generics, biosimilars, and brand-name drugs, and it is fair to point out that this compares with how drugs are paid now, with the likes of Walmart ($4/30 day or $10/90 day fill for over 100 generics) and Amazon (flat $5/month for Amazon Prime members that sign up for RxPass for unlimited number of covered scripts, and 30-day fill for 50 of the most common generic drugs). This comes at a time, Myers points out, when 90% of US prescriptions are generic, but 80% of US spending on drugs are branded, according to FDA data.

Is Cost Plus Drugs a ‘breakthrough’ delivery model?

Being that there are old mail-order pharmacies out there, Barton says, the “breakthrough” is the fact that the Cuban name is behind it; Cuban is also pointing out a market inefficiency, but he raises the question, can this model successfully go beyond generics and biosimilars?

Cooper agreed, pointing out that the entrepreneur does not normally put his name behind ventures, suggesting that he is supportive of cause disruption in the system—his model eliminates the intermediary (PBMs) and instead goes straight to the patient. However, there are currently only 2 million patients benefitting, a small subset of the population.

And just for context, Mitta reminded the audience that 15-20% of Part D beneficiaries use cash-pay pharmacies.

Time will tell in terms of how CMS’s MFP initiative will impact the marketplace for single-source drugs and biological products.

 Is Mark Cuban Really Solving the Drug Pricing Problem? June 27, 2023. DIA 2023, Boston.

Session explores practicality of models for selling low-cost drugs.

DIA 2023: Solving the Drug Pricing Problem

Day one of DIA featured impactful session after impactful session, and “Digital Endpoints in Critical Trials, Qualifications, Collaborations, and Risk-Based Approaches” fit the mold. Discussions were led by Rasika Kalamegham, PhD, Genentech’s Director of US Regulatory, while also featuring Paul Strijbos, Senior Principal Neurotech Innovation Leader, F. Hoffmann-La Roche Ltd; Michelle Campbell, Associate Director, Stakeholder Engagement and Clinical Outcomes, ON, OND, CDER, FDA; Solange Corriol-Rohou,Senior Director, Global Regulatory Affairs & Policy, R&D, Europe, AstraZeneca; Andrew Elias, Associate Director, Global Regulatory Affairs, Immunology, Janssen; and Andrew Potter, Mathematical Statistician, OB, OTS, CDER, FDA.

DIA session, "Digital Endpoints in Critical Trials, Qualifications, Collaborations, and Risk-Based Approaches, June 26, 2023. DIA 2023, Boston. Image Credit: © Nicholas Saraceno.

It is important to note that there were various aspect to this presentation, but a focal point was a case study revolving around digital health technologies (DHTs), specifically Stride Velocity 95th Centile (SV95C), a regulatory-qualified digital outcome measure for use in pivotal studies that was co-invented by Strijbos, who presented on the challenges not only surrounding the development a digitally-derived endpoint, but on applying them for regulatory decision-making. SV95C collaborated with Syde wearable technology for use in for use in Duchenne Muscular Dystrophy trials, and in 2019, became the first wearable-derived digital clinical outcome assessment (COA) qualified by the European Medicines Agency (EMA) for use as a secondary endpoint in trials, according to the National Library of Medicine.

He notes that new technology and endpoint development requires multi stakeholder involvement and long-term commitment—featuring pre-competitive collaboration between patients, engineers, physicians and industry—while suggesting that multiple insights be taking into account, including that of:

With SV95C being a digital measure of peak ambulatory performance that represents the velocity of the 5% of fastest strides taken, Strijbos took attendees through the data that supplemented these claims. And to conclude his portion of the presentation, he explained that there are also potential opportunities for future applications of Syde in the neuroscience space, with there being opportunities for streamlining the qualification procedures.

Speakers dive into the importance of risk-based methods and central-monitoring solutions as they pertain to these trials. 

Nicholas Saraceno

Articles

DIA 2023: The Future of Biosimilars, Interchangeables

DIA 2023: The Impact of the IRA

DIA 2023: Solving the Drug Pricing Problem

DIA 2023: Digital Endpoints in Clinical Trials