Dr Ivo Abraham Column: 1 Billion People Can Access Biosimilars; What About the Other 7 Billion?

A couple weeks ago, the 8 billionth person was born. Where? We shall never know but there is, roughly, an 85% chance it was not in a high-income country. Think of how many people live in countries where quality biosimilars are available—say, for the sake of argument, about 1 billion. Add to this that the future of biosimilars relies, to a large extent, on their commoditization, as I argued in last month’s column.

Not a perfect storm

A promising opportunity

Time to Think 7 Billion

Let me introduce the concept of LMICs— an abbreviation for the World Bank’s classification of countries as low- and middle-income countries. The World Bank does so based on a country’s gross national income (GNI) per capita. A low-income country (LIC) is one with a GNI per capita of $1,085 a year or less. Divide that by 365 days: that’s what, on average, a person in a LIC lives on daily—yes, $2.97 a day. To be considered a lower middle-income country, the GNI per capita rises to a maximum of $4,255 per year—$11.66 per person per day. Then, the upper middle-income countries have a GNI per capita up to $13,205 per year—$36.12 per person a day. Above that is considered a high-income country—the United States comes in at a multiple of that.

Where are the biosimilars commodity markets? This map should give you an idea of where the present is and where the future lies; where people’s health care needs are met and where they are not; and where the other 7 billion are.

1 billion biosimilar worldwide

7 billion in-need worldwide

Responsible and Pragmatic

You might expect this column to go down the usual path of armchair compassion and soft guilt-tripping. Let’s be responsible and pragmatic instead and consider 4 elements:

One, the 1 billion have a commoditized asset (biosimilars) but too many choices (how many adalimumab biosimilars?) from too many manufacturers (some on an insecure economic footing). The 1 billion have the capacity, but with the flood of some biosimilars, there is, realistically, a risk of excess production output or a risk of underutilized production capacity.

Two, there is a massive unmet need for health care among the remaining 7 billion people. Health care is their right, just as it is ours.

Three, the latest WHO Model List of Essential Medicines lists several biologics for which biosimilars are available: trastuzumab, bevacizumab, rituximab, infliximab, adalimumab, etanercept, epoetin alfa, filgrastim, enoxaparin, and several insulins (and I may have missed a couple).

1 billion with capacity—at risk of underutilization

7 billion with a right—in search of sustainability

Context, Equity, and Fairness

Among the most influential books I read professionally was the doctoral dissertation of a neighbor of my parents in Belgium. Rudi Daems once referred to his dissertation as a “mid-life event” in an impressive industry career in vaccines and other medicines for the developing world—member of the World Bank’s Global Advisory Group on Innovative Financing Systems, member of the GAVI Alliance Executive Committee, Chair of the Global Executive Committee for Biologicals and Vaccines of the International Federation of Pharmaceutical Manufacturers and Associations, various task forces of the G7/G8 countries—and the list goes on.

His book helped me understand the larger context—a context of intellectual property (IP) and licensing; pricing; capacity building, from infrastructure to people; and industry. It helped me place medicines for the developing world within a framework of striving for equity with reasonable fairness to all parties.

Responsibility by 1 billion

Accountability by 7 billion

Who, What, Where, and How?

No doubt, whether a country is classified as a low- or a middle-income country, there is a need for assistance—epidemiologically and economically. What should the 1 billion offer, and what should the 7 billion assure?

Act Global and Act Local

Commoditizing biosimilars through global expansion is not all about shifting the current (excess?) capability and capacity in North America, Europe, and high-income Asian countries to LMICs. Several middle-income countries have a biosimilar industry of their own, and this should be encouraged, supported, complemented, or aligned in partnerships. In fact, as the (now completed) Biocon acquisition of the Viatris biologics portfolio underscores, capacity will indeed depend on fostering a global market for biosimilar development, production, and distribution.

Global and local sourcing

Know-how

In the early European days of biosimilars, Ajay Singh of Harvard Medical School and Brigham and Women’s Hospital told me personally that he was able to acquire biosimilar epoetin alfa samples manufactured in 13 LMICs and had them analyzed at 3 laboratories in terms of physical characteristics, activity, and impurities. The findings were rather disturbing: 26 did not conform to European specifications, 22 included additional basic isoforms, that may affect clinical efficacy, 2 were contaminated with bacterial endotoxins; and 17 contained more than 2% aggregates that may influence immunogenicity. Soon thereafter, came the equally disturbing report out of Thailand of 23 cases of patients with chronic kidney disease treated with a locally sourced epoetin alfa biosimilar who developed epoetin neutralizing antibodies and pure red cell aplasia.

This is not cause for finger-pointing. It is cause for pointing at key contributions that the 1 billion who have access in the world can make. Provide quality assessment and quality assurance help to nascent biosimilar industries. Offer regulatory support, preferably in coordination with the WHO and other international organizations. In this, share and customize standards, processes, and systems and technical support in the transfer and local application of approval dossiers.

Access

The conflict in the late 1990s regarding access to HIV/AIDS medicines brought the issues of IP and licensing to fore—claims on one side (advocates and activists) to negate IP rights and stubborn resistance on the other side (industry and regulators) to preserve these rights in their current form. Rudi Daems elaborates on the issues very well in his book, and explains the importance of systems and processes that foster innovation (including protection) but enable responsive, responsible, and fair licensing. Let the HIV/AIDS experience be a foundation upon which to build a solid system of access to biosimilars.

Access is also determined by pricing—differentiated pricing, that is, based on local need, affordability, and economic equitability. Though not related to biosimilars but informative nonetheless, Mavis Obeng-Kusi in my group at the University of Arizona led a study that showed that Ebola vaccination in response to an outbreak in a hypothetical rural community of 1000 inhabitants in the Democratic Republic of Congo (DRC), a low income country, was cost-effective in reducing infections, and averting deaths and disability-adjusted life years. She followed this up with a study of value-based pricing for the DRC, Liberia, Sierra Leone, and Uganda. That resulted in separate (that is, differentiated) estimates for each country based on the intensity and consequences of an Ebola outbreak, vaccination rates, age, life expectancy, and the country’s gross domestic product (GDP). These findings can be applied in concept to biosimilars as well: differentiated pricing based on local disease burden and economic status.

Several other factors affecting access merit a brief mention. Access to biosimilars in LMICs is not merely a matter of availability, but also of education, training, capability building, and capacity management. It requires both a distribution infrastructure and distribution system. Marketing should be ethical and adhere to high-income country standards.

Unfortunately, there is also the danger of theft, black-marketing, product manipulation, not to mention graft by government officials and other forms of corruption. This is an area where LMICs need to take the initiative.

Fair protection and pricing

Capability, capacity, and infrastructure

Self-governance but no crime

Middle-income vs Low-income Countries

It is striking, if not discouraging, that most practical solutions offered focus on middle-income countries. It is not surprising either. These countries tend to have good if not very good health care systems, though perhaps not with the access of the 1 billion countries. They may have some form of public assistance as well as health insurance schemes. The encouraging news is that about 6 billion people live in lower-middle and upper-middle income countries.

In a 2019 brief on biosimilars in emerging markets, McKinsey & Company present 4 innovative pricing models for biosimilars. One was patient-assistance programs in which the price of a biosimilar is reduced to patients who cannot afford the full price. In fact, think of this as prices further reduced after the reduction from the high-income country price.

Another one was dual branding, where the same biosimilar would be available “under different brands at different price points to target different affordability segments” (this might require some caution, though, as the Semglee vs unbranded insulin-glargine-yfgn situation in the United States taught us). Two pricing models hold, I think, real innovative potential but how they would be implemented is not described very well. Micro-insurance refers to “collaborations between biosimilar manufacturers and local insurance companies to provide policies offering patients affordable care”. Micro-finance “is a way to offer payment by installments”.

Ideas in search of proof.

This may work in middle-income countries, but compare this to low-income countries with a much more limited health care infrastructure and, apart from some public assistance, inadequate or virtually no health insurance schemes. Let’s be honest: we will have to help these countries—to some extend unilaterally through international aid, but potentially also bilaterally through mutual exchange and collaboration agreements—fair agreements, that is, and to be blunt, not some form of neo-colonialism. Think of it as “fair trade biosimilar adalimumab for fair trade coffee”.

Commodity for commodity.

Bio

Ivo Abraham is Chief Scientist of Matrix45 and Professor of Pharmacy, Medicine, and Clinical Translational Sciences at the R. Ken Coit College of Pharmacy at the University of Arizona, where he is associated with the Center for Health Outcomes and PharmacoEconomic Research. He has worked in biologicals since the late 1990s and in biosimilars since their introduction in the European marketplace—collaborating closely with Karen MacDonald (also his wife) on large international and national observational studies. On both the private and academic sides, their group published the first economic evaluations of biosimilars, a line of studies that continues to date and have been instrumental in the breakthrough and market adoption of biosimilars in Europe and the United States. More recently, Matrix45 has ventured into biosimilars in emerging markets, including low- and middle-income countries. Ivo Abraham may be reached at cntr4biosim@matrix45.com.

Perspective

I am a strong proponent of biosimilars. That does not mean I am against innovation—on the contrary. There would be no biosimilars without the innovators. I have worked on several of these innovators. I am working now on innovators that someday may have biosimilar analogs. I am of the generation that has had the joy of seeing treatments emerge (and some fail) for diseases that over 40 years ago had the poorest of poor prognoses—but are now treatable.

Innovation in therapeutics (that is, the originator products) is about moving the boundaries of hope. Biosimilars are a channel for spreading more hope to more patients.

Statement of Disclosures of Relevance to This Monthly Column

Matrix45, LLC and predecessor companies in which Ivo Abraham and Karen MacDonald hold or have held equity, have been contracted for research, analytics, dissemination, and consulting services by Janssen/Johnson & Johnson, Amgen, Novartis, and Roche on the originator side and by Sandoz/Novartis, Coherus Biosciences, Mylan/Viatris/Biocon, Hospira/Pfizer, and Teva on the biosimilars side; with past and current conversations with Merck KGaA, Therapeutic Proteins International, Celltrion, Apobiologix, Apogenix, Fresenius Kabi, and Spectrum. By company policy, associates of Matrix45 cannot hold equity in sponsor organizations, nor provide services or receive compensation independently from sponsor organizations. Matrix45 provides its services on a non-exclusivity basis.

All contributions to this column are prepared independently and without funding from sponsors.

Links to Prior Columns

Biosimilars and the Commoditization of Treatments (October 2022). https://www.centerforbiosimilars.com/view/dr-ivo-abraham-column-biosimilars-and-the-commoditization-of-treatments

When more may yield less: price erosion of biosimilars following US market entry. (September 2022).https://www.centerforbiosimilars.com/view/dr-ivo-abraham-column-when-more-may-yield-less-price-erosion-of-biosimilars-following-us-market-entry

It’s what we do with the savings: economics and equity. (August 2022) https://www.centerforbiosimilars.com/view/dr-ivo-abraham-column-it-s-what-we-do-with-the-savings-economics-and-equity

Good bait and fair switch: biosimilar interchangeability, substitution, and choice. (July 2022) https://www.centerforbiosimilars.com/view/contributor-good-bait-and-fair-switch-biosimilar-interchangeability-substitution-and-choice

To try or not to try, that’s not the question: phase 3 trials of biosimilars and beyond. (June 2022) https://www.centerforbiosimilars.com/view/contributor-to-try-or-not-to-try-that-s-not-the-question-phase-3-trials-of-biosimilars-and-beyond

The enemy of your enemy should be your friend: why biosimilar companies should collaborate. (May 2022) https://www.centerforbiosimilars.com/view/contributor-the-enemy-of-your-enemy-should-be-your-friend-why-biosimilars-companies-should-collaborate