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Our first white paper, Biosimilars Come of Age, highlighted growth in Biosimilars from 2015 to 2020. Vast majority of the world has moved into the Established Phase for Biosimilars. EU and India are in the Required Phase with others close behind.

As mentioned in white paper I, the major question in the biosimilar industry is sustainability. Many companies have come and gone in the biosimilars space. Are biosimilars only viable for first wave blockbuster products? Are prices being driven too low to justify development of biosimilars that will enter the market in the back half of the decade? Who will develop biosimilars for smaller revenue products?

Our goal is to outline what we believe is a viable path to ensure biosimilars are available for practically all biopharmaceuticals regardless of market size. We will show over a series of articles how we believe one can build a profitable business of biosimilars earning IRRs of over 30% including the cost of building manufacturing facilities, developing products and commercialization with little risk. How many other pharmaceutical projects can match this at the beginning of a project?

In this second white paper, Evolution of the biosimilars Industry, we focus on how industry players have entered and, in some cases, exited developing and commercializing Biosimilars. This is helpful to predict how the market will continue to develop.

In the early 2000s, companies started to develop what were then called “follow-on biologics”. Most of the initial players developing products were either generics companies or in some cases startups. The belief was “follow-on biologics” would eventually follow a generic industry path. Major pharmaceutical and biopharmaceutical companies weren’t interested in these products.

Sandoz, which became part of Novartis and originally started producing biopharmaceuticals as a CMO, was the first major player to enter the biosimilar industry. They remain one of the key players today. Other companies like Teva acquired smaller companies with biosimilar portfolios and attempted to develop their own products. By the early 2010s, many major pharma companies had biosimilar development efforts, others like Biogen and Merck formed partnerships, many smaller companies including startups dedicated to biosimilars entered the field and generics companies from emerging markets (e.g. Argentina, India, Russia, etc.) entered into major partnerships to bring their “biosimilars” to the US/EU. Only a handful of biopharmaceutical companies, notably Genentech/Roche, stated they would not develop biosimilars and focused instead of developing new therapies.

This large effort involving more than 30 different companies from around the world developing a small number of products and focused mainly on less than 15 “blockbuster” products inevitably led to consolidation. Only one startup, Coherus, survived to commercialize its own developed product in the US or EU. Many large pharma companies including both Merck and Merck Serono KGA decided to exit the field after significant investment and in some cases like Pfizer launching products.

What is left are three categories of companies which can be categorized as the developers, the commercializers and the integrators. Another group, the exiters, choose to exit the biosimilar industry and focus on other priorities, presumably because other priorities have higher returns. We profile the following leading biosimilar players, grouped into their respective categories:

The developers: Develop biosimilars for global markets. May commercialize by themselves in domestic and emerging markets. These companies have the technical skills to develop products but realize commercialization in developed markets requires specific skills and payer/trade relationships one cannot build just for biosimilars.
- Samsung Bioepis, Biocon, Dr Reddy’s, Lupin, Biothera, Henlius, Prestige, Biocad
The commercializers: Focus on commercializing in-licensed products in developed markets. These companies leverage their ability to get products approved and existing payer/trade relationships to bring biosimilars to market. They don’t have the internal technical expertise to develop biosimilars
- Mylan, Teva, Apotex
The integrators: Develop both internally developed and in-licensed products and commercialize in developed markets, find local distribution partners in emerging markets. There are only a few companies with the combined technical and commercial skills to develop and market biosimilars in developed markets. Apart from Coherus, all have established biopharma businesses and capabilities prior to entering biosimilars.
- Sandoz, Amgen, Coherus, Celltrion
The exiters: Prioritized Biosimilars and then decided to exit and focus on core business
- Pfizer, Merck, Momenta

Specific company journeys are shown in the attached “network” diagrams.

Company journeys raise questions such as

Who is going to develop the next wave of biosimilars for the commercializers? Mylan is a good example to consider. Their main source of products to date has been Biocon. Biocon’s next wave of products are licensed to Sandoz for Developed Markets. Will Mylan continue to bring biosimilars to market?
Will Biosimilar development now be focused in companies based in China, India and Korea given most development efforts by EU/US major pharma have stopped and no new startups are entering the field? Will these development companies try to move forward to commercialization in developed markets as some are trying to do, e.g. Celltrion with infliximab? If so, how will Developers prioritize products going forward?
To date only large multi-billion-dollar products have been extensively developed as biosimilars. Will Developers or Integrators start to develop products with smaller dollar potential?

In our next white paper, we will list out the products that should be developed going forward and in future white papers outline what we believe is a viable path to ensure biosimilars are available for practically all biopharmaceuticals regardless of market size.

Legend:

These symbols will aid in reading the network diagrams that appear in the following pages, representing the period from 2002 to till date

Developers: Samsung Bioepis, Biocon, Dr Reddy’s, Lupin, Biothera, Henlius, Prestige, Biocad

Commercializers: Mylan, Teva, Apotex

Integrators: Sandoz, Amgen, Coherus, Celltrion

Exiters: Pfizer, Merck KGaA, Momenta

Sources: Corporate press releases, GABI, The Center for Biosimilars, SBLehrer LLC and IBPS analysis

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IBPS and SBLehrer LLC are releasing the next update of clinical efforts for treatments and vaccines for Covid19. As we stated when we started this effort, Our goal is to highlight the actual work and results from studies around the world to aid in decision making, not follow the 24 hour news cycle hype.

We are currently tracking worldwide progress on the following:

– Prophylaxis treatment of Covid19 for at risk Population like Medical staff

– Treatment options for Infected Patients

– Vaccines for Healthy People

There are 62 drugs being studied in over 2000 trials worldwide. Major study results will be released in the next 6 weeks. Major treatment updates include:

–Dexamethasone – This corticosteroid showed significant improvements in late stage, critically ill patients in a large UK study. The UK has already authorized use and we expect other regulatory agencies will follow

–Hydroxychloroquine – Clinical data now shows hydroxychloroquine not only has no clinical benefit in Covid-19 patients, the cardiac side effects make this treatment unsuitable for Covid-19 patients. US FDA and other regulatory agencies have withdrawn their emergency use authorizations for Covid-19 patients.

-Preliminary Data Suggests Low-Dose Radiation May Be Successful Treatment For Severe Covid-19

135 vaccine candidates are in development; 8 are in clinical trials with 2 entering phase III trials this summer. 5 vaccines have been selected by the US Gov’t “Warp Speed” program to ensure commercial quantities are available as early as the end of 2020.

As we update this summary, please help us by adding any information you see missing.

Thanks for your help in this journey

In the 1990s, it was “generic biologics”. In the early 2000s, “follow-on biologics”. Starting in 2006 regulators settled on the word “biosimilars.” The goal was always the same, produce equivalent versions of blockbuster complex products made by living cells to help manage cost and increase access, just like what occurred with generic pharmaceuticals.

Reaction was swift. Innovator biopharmaceutical companies parroting the same language and approaches used by the pharmaceutical industry in the 1980s to say a “generic pharmaceutical” wasn’t possible tried to ward off biosimilars – biopharmaceuticals are too complicated to reproduce, patient safety will be an issue if one switches between the innovator product and a biosimilar, etc. The arguments were almost identical to those from the 1980s. However, in the end, science and clinical evidence wins. Biosimilars are here and we have seen many innovator companies joining the race along the way.

It wasn’t until 2015 when US FDA approved the first “biosimilar,” Sandoz’s Zarxioâ, could the industry be sure there would be a worldwide biosimilars business. A lot has happened in 5 years. Now the major question has shifted to sustainability. Many companies have come and gone in the biosimilars space. Are biosimilars only viable for first wave blockbuster products? Are prices being driven too low to justify development of biosimilars that will enter the market in the back half of the decade? Who will develop biosimilars for smaller revenue products?

To address these questions, SBLehrer LLC and Integrated Biopharma and Pharma Solution, Ltd. (IBPS) have teamed together to produce a multipart series regarding the biosimilar industry. We take a pragmatic, battle-scarred view. We have worked on “biosimilars” since the late 1990s. Collectively we have developed several biosimilars worldwide. We have assisted governments writing Biosimilar Guidance Documents and Regulations. We have built facilities producing monoclonal antibody biosimilars at $7 per 100mg vial of “final package product out the door” including all fully loaded manufacturing costs. This will enable cancer treatment for a few dollars a day for these important biopharmaceutical treatment options. We have seen what works and what doesn’t.

Our goal is to outline what we believe is a viable path to ensure biosimilars are available for practically all biopharmaceuticals regardless of market size. We will show over a series of articles how we believe one can build a profitable business of biosimilars earning IRRs of over 30% including the cost of building manufacturing facilities, developing products and commercialization. This is with little risk. How many other pharmaceutical projects can match this at the beginning of a project?

This first installment starts with a look at the last five years and how market acceptance has evolved for biosimilars. We use five stages:

Nascent: initial products, regulators are still learning how to review and approve biosimilars, the market is unsure of when to use biosimilars
Adopting: first wave of products is approved and marketed, but still only a handful and biosimilars don’t fundamentally change access or affordability
Recognized: More products approved, predictable regulatory pathways, several products now have multiple approved biosimilars; payers and healthcare providers setting up policies for use of biosimilars
Established: patients, payers and healthcare providers understand and routinely use biosimilars
Required: patients, payers and healthcare providers expect biosimilars to be approved and marketed as soon as legally permissible; some government-based healthcare providers assume launches and make budget decisions based on expected price reductions.

Source: Public Trial/Approval Registries, Gabi, Drug Patent Watch, Springer, SBLehrer LLC and IBPS Analysis

As one can see in the Changing Global Landscape of Biosimilars, the vast major of the world has moved into the Established Phase for Biosimilars. The EU and India are in the Required Phase. Clearly Biosimilars have “Come of Age”.

Our next installment will focus on how current industry players evolved. This is helpful to predict how the market will continue to develop.

We are currently tracking worldwide progress on the following:

– Prophylaxis treatment of Covid19 for at risk Population like Medical staff

– Treatment options for Infected Patients

– Vaccines for Healthy People

Several major development occurred since our last update.

Anti-virals: The big new was Emergency Use Approval by US FDA and Japanese Approval for Remdesivir which showed Remdesivir cut hospital stays by 31 percent compared to a placebo. Gilead Sciences also reached agreement with several leading Generic Drug Manufacturers to ramp up production worldwide. Equally impressive is progress seen in trials with other anti-virals such as Lopinavir/ Ritonavir in combo with an old antiviral Ribavrin and INF-Beta and separate trials with Favipiravir show promising initial results. One imagines this will look like HIV/AIDS where a combination of anti-virals depending on whether given early or later in disease progression. More trial data is needed to determine which anti-viral works best throughout the course of Covid19 infection.
Hydroxychloroquine: Hydroxycholorquine was the early front-runner of a viable treatment. Recent data is showing limited efficacy. Given the drug has know Long QT/ Ventricular tachycardia side effect, it is not generally safe for everyone to use. US FDA amended its Emergency Use Approval for use only when in a hospital setting where side effects can be managed. Robust clinical trials are ongoing to determine where best to use Hydroxycholorquine for treating Covid19
Stem cells continue to show positive signs. Three additional trials showed very high recovery rates with severe patients. Almost 100 patients have seen significant improvement with use of stem cells
Biopharmaceuticals for auto-immune disease slowing down the “cytokine storm” to show positive signs using various IL antagonists was an early leading approach with the assumption the “cytokine storm” was causing patients to rapidly decline. Trial data to date is very mixed with some promising data in severe patients. Similar to Anti-virals more trails will be needed to see when to best use these drugs and the associated benefits.
In the Vaccine world there was lots of early data showing various vaccine candidates appeared safe and subjects developed SARS-Cov-2 antibodies/spike protein Antibodies. Moderna and CanSino Biologics had the most promising human data, although very limited in scope. Equally important, basically all leading Vaccine Candidates are lining up the necessary manufacturing capacity to manufacture ”at risk”. The goal is to have 100’s of millions of doses of vaccine available by early 2021 if any leading candidate continues to show promise. While most will fail, Governments led by the US are funding this production to ensure rapid distribution of any vaccine demonstrating safety and efficacy

We look to update this summary in the next two weeks. As before, please help us by adding any information you see missing from the summary.

Thanks for your help in this journey

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Of the +1500 trials registered on various clinical websites we are currently tracking the progress on the following

– Prophylaxis treatment of Covid19 for at risk Population like Medical staff

– Treatment options for Infected Patients

– Vaccines for Healthy People

Several major development occurred since our last update.

Hydroxychloroquine: Initial reports from France and the US show hydroxychloroquine in combination with Azithromycin showed promise. Governments around the world are stockpiling the drug. US FDA authorized use for patients who were not enrolled in clinical trials. Trials in Brazil and the US with hydroxychloroquine were recently stopped due to significant cardiac side effects, a known side effect of the drug. FDA on April 24th, advised doctors against prescribing hydroxychloroquine or the related drug chloroquine to coronavirus patients outside of the hospital setting as it appears to be causing some serious and potentially life-threatening side effects. A small trial of 30 subjects has demonstrated despite its small sample size that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin. Another small study in Chins is also exhibiting positive preliminary outcomes
Remdesivir: Similar to Hydroxychloroquine, Remdesivir has had its own roller coaster in the last 2 weeks. Worldwide equity markets rose more than 10% after initial promising compassionate use results on ~120 patients were released. New data issued by WHO from a Chinese study which had to stop recruiting after the drug failed to show any effect caused major headlines around the world. Meanwhile Gilead has further increased its enrollment numbers for 2 trials which are currently ongoing and expected to end in May-2020.
Stem cells are showing positive signs. Two small studies showed very high recovery rates with severe patients
In the Vaccine world which is currently the most promising of all alternatives under development, WHO currently tracked 71 vaccines in development across the globe of which 8 have moved into clinical phase

We look to update this summary in the next two weeks. As before, please help us by adding any information you see missing from the summary.

Thanks for your help in this journey

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COVID-19 has many names; Coronavirus, Covid-19 or SARS-CoV-2. Regardless of what we call the virus, the worldwide pandemic the virus created is prompting an unprecedented amount of research and experimentation to find both therapeutic treatments for Covid-19 and a vaccine to help prevent the next seasonal wave, given Covid-19 is not simply going away anytime soon. Academic researchers, non-profits, companies, health organizations and governments are cooperating in ways and timeframes unimaginable just 8 weeks ago. Potential “cures” and “wonder drugs” ricochet around the globe faster than anyone can follow. Healthcare professionals are using hypothesis about mechanisms of action and relying on small observational studies to make treatment decisions in real time with both rapidly deteriorating patients to try to save lives and at the same time attempting to prevent stable patients from entering rapid decline which is a hallmark of Covid-19.

We at Integrated Biopharma and Pharma Solutions and SBLehrer LLC will be summarizing the data coming from trials going on around the world. Unfortunately the 24 hours new cycle can only focus on the sound bites and the latest disagreements between policy markets and the medical community. We hear of “anecdotal” evidence vs. “real science”. There is no time to fully explore what is working and what is not. Our goal is to highlight the actual work and results from studies around the world to aid in decision making.

We start with summarizing the actual clinical trials being conducted across the world for therapeutic solutions to treat Covid-19 patients. As of April 06, 2020, we count 41 trials with specific inclusion/exclusion criteria on patients with 34 separate treatments being started in 21 countries around the world. You will see the specific treatment arms proposed, the planned number of patients and expected timelines. We also are building a database of all the various vaccine approaches. To date we count 62 proposed vaccines with many more being discussed.

No one group looking at this can track all the trails. Most only focus on a few countries and will miss work occurring outside of well-known medical centers. Frequently the best learning happens away from the glare of the spotlight. Please help us make this as complete as possible. Reply to this post with trials we are missing.

Every 2 weeks we will send out the update and include any learnings we find along the way.

Hopefully in the next few weeks life will start to move away from the current “stay at home” and “social distancing” approach to managing the pandemic given we have no other tools to use today. We will see how the world slowly gets back to a new “normal”. The 24 hour new cycle will start to shift. However this work will continue. The world wants to be ready when new hot spots re-emerge.

Thanks for joining us on this journey