Category Archives: Biologics

Launch of first breast cancer biosimilar in the UK

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

MSD has announced the launch of Ontruzant®, (trastuzumab), a biosimilar referencing Herceptin® (trastuzumab/TRZ), for the treatment of early breast cancer, metastatic breast cancer and metastatic gastric cancer.

This was the first trastuzumab biosimilar to receive regulatory approval in Europe and is the first to launch in the UK.

Biosimilar trastuzumab represents the first product approved in the UK under a global biosimilars development and commercialisation agreement between MSD and Samsung Bioepis Co Ltd.

The European Medicines Agency (EMA) requires biosimilars to show they are highly similar to the reference medicine in terms of structure, biological activity and efficacy, safety and immunogenicity profile. Ontruzant (trastuzumab biosimilar (SB3)) is a monoclonal antibody and has been shown to have similar safety and efficacy as its reference product Herceptin (TRZ) in early breast cancer, with breast pathologic complete response rates (bpCR) being 51.7% and 42.0% with SB3 and TRZ respectively. The adjusted ratio of bpCR was 1.259 (95%CI, 1.085 to 1.460), which was within the predefined equivalence margins. The adjusted difference was 10.70% (95% CI, 4.13% to 17.26%), with the lower limit contained within and the upper limit outside the equivalence margin. The overall response rates were 96.3% and 91.2% with SB3 and TRZ.

Dr Mark Verrill, Head of the Department of Medical Oncology at the Newcastle upon Tyne Hospitals NHS Foundation Trust, and the deputy lead clinician for breast cancer in the North of England Cancer Network said, “This is good news for so many cancer patients and the NHS. The launch of biosimilar trastuzumab provides a high-quality treatment alternative for patients, while offering significant potential savings for the NHS. The biggest category of medicines in oncology is monoclonal antibodies and the introduction of biosimilars such as trastuzumab could provide a substantial cost saving.”

Denise Blake, Senior Lead Clinical Pharmacist at Newcastle Hospitals, explains, “The introduction of biosimilar trastuzumab provides an opportunity for the NHS to realise substantial financial savings without compromising patient care. Close collaboration between oncologists, pharmacists and nursing staff is required to ensure a seamless introduction into routine clinical practice.”

“As a company committed to inventing new treatment options for both common and neglected types of cancer, MSD is also pleased to be offering the NHS a biosimilar medicine in an established area of care. Biosimilar trastuzumab marks a significant milestone for both MSD and the oncology community, providing the UK’s first biosimilar trastuzumab, based on our collaboration with Samsung Bioepis,”explains Louise Houson, UK Managing Director, MSD.

Regulatory approval was based on a Phase III study that compared SB3 with reference TRZ in patients with human epidermal growth factor receptor HER-2 positive early breast cancer in the neoadjuvant setting.

The study showed the total pathologic complete response rates were 45.8% and 35.8% and the overall response rates were 96.3% and 91.2% with SB3 and TRZ, respectively. Eight hundred patients were included in the per-protocol set (SB3, n = 402; TRZ, n = 398). The bpCR rates were 51.7% and 42.0% with SB3 and TRZ, respectively. The adjusted ratio of bpCR was 1.259 (95%CI, 1.085 to 1.460), which was within the predefined equivalence margins. The adjusted difference was 10.70% (95% CI, 4.13% to 17.26%), with the lower limit contained within pre-specified equivalence margins and the upper limit of the confidence interval slightly exceeding the pre-specified equivalence margins (-13%, 13%).

Overall, 96.6% and 95.2% of patients experienced one or more adverse event, 10.5% and 10.7% had a serious adverse event, and 0.7% and 0.0% had antidrug antibodies (up to cycle 9) with SB3 and TRZ, respectively.


The FDA commissioner just laid out how ‘everybody wins’ in the US healthcare system except the patients

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

  • FDA Commissioner Dr. Scott Gottlieb put the pressure on health insurance companies and pharma middlemen about the high drug prices patients are facing at a health insurance conference on Wednesday. 
  • “Sick people aren’t supposed to be subsidizing the healthy,” Gottlieb said. “That’s exactly the opposite of what most people thought they were buying when they bought into the notion of having insurance.”
  • Gottlieb’s interested in making the market for biosimilars — essentially generic versions of biologic drugs that could save the US billions — more competitive, something that has proven challenging so far. 

FDA Commissioner Dr. Scott Gottlieb has health insurers in his crosshairs.

Speaking at a policy conference hosted by America’s Health Insurance Plans, the lobby that represents health insurers, Gottlieb called out the practices insurers and pharmaceutical middlemen use that keep prices high for patients.

The Food and Drug Administration, which Gottlieb oversees, is responsible for regulating food and drugs, as well as medical devices, blood donations, veterinary products, cosmetics, and tobacco. While he has oversight into whether or not a drug is approved, the agency does not play a role in determining how much the medication costs once it’s on the market.

Even so, he did not mince words when it came to pointing out the shortcomings of the way those prescriptions get paid for.

“The top three PBMs control more than two-thirds of the market; the top three wholesalers more than 80%; and the top five pharmacies more than 50%,” he said, referring to pharmacy benefits managers, which negotiate lower prices for brand-name medications. “Market concentration may prevent optimal competition. And so the saving may not always be passed along to employers or consumers.”

That’s putting pressure on patients when they show up at the pharmacy counter.

“We continue to see a backlash against these Kabuki drug-pricing constructs — constructs that obscure profit taking across the supply chain that drives up costs; that expose consumers to high out of pocket spending; and that actively discourage competition.”

That can lead to those with chronic conditions paying more for their medication, often close to the list price if they have a high deductible health plan that leaves them on the hook for paying a certain amount before insurance kicks in. And because the rebates drug companies pay to insurers and middlemen are still getting paid, that cost gets absorbed into lowering premiums for everyone who’s insured, healthy and sick alike.

“Sick people aren’t supposed to be subsidizing the healthy,” he said. “That’s exactly the opposite of what most people thought they were buying when the bought into the notion of having insurance.”

The insurers and the pharmaceutical middlemen need to own their role in the pressure it’s putting on patients, Gottlieb said.

“Now I understand that there’s a perverse incentive to use that rebated money to lower premium costs, since most health plans compete on the sticker cost of their premiums,” he said. “But we’re living in a world where financial toxicity is a real concern for patients. And every member of the drug supply chain needs to take responsibility for addressing it.”

Gottlieb’s bringing this responsibility up due to his interest in making the market for biosimilars — essentially generic versions of biologic drugs that could save the US billions — more competitive, something that has proven challenging so far.

Because of how rebates get paid out, there’s not a lot of incentive to use a cheaper version of the biologic drug, which keeps costs high.

“Everybody wins. The health plans get the big rebates. The PBMs get paid on these spreads. And branded sponsors hold onto market share,” he said. “Everyone that is, but the patients, who in the long run, don’t benefit from the full value of increased competition Congress intended.”

On Tuesday, the biggest health insurer in the US, UnitedHealthcare, said that starting in 2019, some of its members on high deductible plans would be eligible to get rebates for their medications. So, for example, if a patient went to the pharmacy for a medication that under their high deductible cost $600, that might get lowered to $300 after factoring in the rebate the insurer receives. Gottlieb called the move a “potentially disruptive step.”

“This could make the difference between patients affording their medicines and remaining adherent, or stopping effective therapy to save on out of pocket costs,” he said.

“Payors are going to have to decide what they want: The short-term profit goose that comes with the rebates, or in the long run, a system that functions better for patients, providers, and those who pay for care.”

SOURCE: www.

How can pharma navigate the complex marketing landscape?

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

The first chapter of pharma’s commercial evolution takes us from the insatiable sales-drive of the 1980s to the present, highly complex marketing landscape.

It is easy to forget that our competitive industry still has 80-90% gross margins and, as a consequence, its traditional commercial model is driven by sales growth, rather than worrying about costs.

Under most circumstances, incremental sales drive incremental profit. Within the affiliates this is obvious, and country managers have often resisted attempts by corporate counterparts to take a centralised approach to sales and marketing, claiming their country’s commercial ecosystem is unique and not amenable to meddling.

Of course, the modern pharma company will also have to conduct market access, medical education and phase IV studies within its affiliates, but the reality is that most affiliate activity is focused on sales. For large pharma companies the sales and marketing budget usually beats R&D budgets by 1.7 times, and this is becoming increasingly difficult to justify.

Rise of primary care dominance

Throughout the 1980s and 90s the focus on sales-driven growth led to the evolution of some very different ways of working within primary care, from co-promotion and co-marketing with embedded local players, to the ‘petal’ system of multiple salesforces detailing overlapping product ranges.

The purpose of these techniques, together with employment of contract sales teams, was a sort of ‘shock and awe’ strategy which swamped the physician with frequent visits about particular products. The competitive response was usually swift and commensurate, resulting in a commercial arms race between players within a hotly contested therapeutic area.

This was known as the ‘share of voice’ model, and when applied to large primary care categories, it drove top line growth so successfully that governments and institutional payers were forced to find a response to escalating drug bills around the world.

Backlash from health technology

This response varied from country to country, but has taken two main forms; the Health Technology Assessment response and the consolidated payer response. Throughout the 1990s and 2000s, in the UK (NICE), much of Europe, Australia and parts of Asia, there has been systematic developing of a process that assesses whether a product represents value for society.

Much of the health economics work is shared among countries, and pricing comparisons made between the same product in different countries are routine. The benchmarks for the monetary value of a healthy human being are the subject of debate, but are necessary to make budgetary choices in a system without unlimited resources.

The consolidated payer model, operating in the US through pharmacy benefit managers such as Express Scripts, relies on large payers exerting pressure on manufacturers for rebates, with some undifferentiated product portfolios having to rebate as much as 50% of their gross price.

The impact of health technology assessments can be seen today, manifesting itself in pricing pressure, therapeutic substitution, a diminution of decision-making by physicians and a conscious shift towards products with a confirmed medical need. A decline in R&D productivity, however, has not made this process easy.

Dead end: Primary care hits a wall

Many commentators blame the decline in R&D productivity for the steep fall in product approvals through the 2000s but, in reality, there have been several forces at work.

The rise in genomics, together with high-speed screening techniques, led to a belief that chemical libraries could be screened against unprecedented targets and that optimised drug candidates would flood through the discovery phase into phase I trials.

The sharp product rise in the early clinical phases then came to a shuddering halt during phase II ‘proof of concept’ studies, when large numbers of clinical failures unveiled the reality – there is no short cut to understanding disease biology.

As research cul de sacs were explored, a squeeze on primary care products began in the form of price pressure from above and greater safety demands from below. As a consequence, and aided by the rise in technology, a rapid increase in the proportion of newly-approved, biological in origin drugs commenced.

Monoclonal antibodies, vaccines, enzyme replacement therapy and other therapeutic peptides, aided by insatiable demand for insulin, developed strong sales and completely changed the nature of commercial interfacing with physicians.

Biologicals change the commercial dynamic

The pressure on primary care products, together with the impact of the patent cliff in 2012/13, have combined to drive sales of primary care products into stagnation. Much of industry downsizing, particularly within commercial operations, has been in response to this.

Perhaps most merger and acquisition activity within pharma also has its origins in this relentless pressure on primary care sales and the need to reload the pipeline quickly with biologicals and specialties.

The success of biologicals and other specialties, such as oral cancer drugs, in terms of both approval and sales, has required the industry to change its commercial emphasis. The huge traditional focus on primary care or family doctors has changed to specialists, and their support workers within a secondary care or hospital environment.

The increased complexity of the specialty sell, sometimes involving multiple decision-makers, formulary approval, health economic arguments, companion diagnostics and performance-related reimbursement, has required a much smaller, but more skilled group of people to interface with the healthcare network.

Many companies have yet to find the necessary mix of skills within their workforce and are still working under the old assumptions that spending on promotional activities can remain as high as it used to be under traditional models. They do so at their peril. Check out Part 2in the next issue, as promotional resources and modern data come under intense scrutiny.


National Market Access Lead, Associate Director

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

Are you truly making a difference?

This is the mantra for our client who focuses on developing innovative therapies for people coping with serious diseases the world over.

If you would consider yourself to be an expert on NHS funding and access policies and have a broad background in developing and executing strategic commissioning and access plans at a National level for highly specialised products, then we would like to speak with you.

Our client is a global biotechnology company with over 40 years of heritage working across multiple specialist therapy areas.

Ideally, we are looking for somebody with a background in developing and executing market access strategies for biologic products , and who is capable of working efficiently in a cross-functional matrix environment.

You do not need to have HEOR experience, however, working knowledge of budget impact modelling would be advantageous.

Why apply?

– Highly visible position working a priority area of the business

– Autonomous position reporting into an incredibly seasoned and empowering industry expert

– Collaborative and innovation focussed business environment

– Industry leading salary and benefits package with a big focus on wellness.


– Initial telephone interview with us on application, if you decide you would like to proceed further, we would submit your details to the hiring manager for review

– The second stage would be a relatively informal first stage interview with the hiring manager to ascertain fit both sides

– If you are still interested, and the hiring manager agrees! There will be an HR interview along with a structured assessment process which will include a variety of stakeholders from the business – it is likely that the process will extend into January 2018. However, our client is keen to close the position down within the next 4-6 weeks.

To discuss this position in detail or for any further information, please contact Wax Selection on 0844 8009021.

Vive la révolution! What is the future of biosimilars in the UK?

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

Harriet Lewis, ABPI’s Medicines Optimisation Lead, discusses the future of biosimilars in the UK asking the pertinent question: will they revolutionise healthcare?

The ABPI represents UK-based pharma companies researching the newest and most innovative medicines. Our members make both originator biological medicines and make biosimilar medicines so, for want of a better word, we have a foot in both camps.

We work to support the introduction of biosimilars but also work to ensure there is a sustainable and active competitive market. To understand why we talk about biosimilars and the biosimilar market in a unique way, it is important to take a step back.

I am a pharmacist — not a scientist — so I am constantly amazed by the science behind biosimilar medicines that is both fascinating and complex. Put simply, biosimilar medicines are made from living cells and since living cells are all slightly different, there are also variations between biosimilar medicines. This so-called heterogeneity is part and parcel of biological medicines: chemical difference that do not affect the clinical effectiveness of the medicine.

When producing biological medicines, companies must demonstrate the reproducibility of their drugs time-after-time and within certain parameters. Before they even get to the point of clinical trials in humans they are required to demonstrate successful reproducibility. As a result of the complexity of manufacturing and regulation, bringing these products to market is time-consuming and expensive.

One of the early key discussion points around biosimilars is how they should be defined and therefore how they should be treated. Biosimilars are neither generic medicines nor novel treatments. Definitive guidance from the European Commission sets out that they are in fact a ‘version of an active substance’ within an already approved medicine.

Manufacturers must convincingly demonstrate the similar nature of these products. Regulators require biosimilars to demonstrate a comparable clinical effectiveness to originator products. The European Medicines Agency (EMA) goes so far as to say that the ‘concept of biosimilarity is applicable to any biological medicinal product’.

Just as with any medicines, there are class-based risks associated with a biosimilar medicine’s pharmacology, potency or bioavailabilty over time, and these are monitored on an ongoing basis. Pharmacovigilance is a necessary component to the success of biosimilars and ensures that regulators can trace where biosimilar medicines are used to track immunogenic side effects should they arise.

We can only know so much about any medicine, including biosimilars, before they are licensed. Information and our understanding of how they work in patient populations is continually built-upon once the medicine become available to patients: pre-authorisation clinical studies are often insufficient in highlighting all adverse effects. Across Europe, the pharmacovigilence regulation requires that all adverse events for biologics are reported by brand name and batch number. In England, prescribers are encouraged to prescribe by brand name and NHS providers to record product name and batch number to provide an audit trial for product identification and traceability.

The impact of biosimilar competition and what comes next

The European biosimilars market has grown exponentially since the first medicine was launched back in 2006; there was a sudden uptick from 2012 and if you look at any timeline outlining the number of medicines launched what is abundantly clear among the many successes are also a number of failures.

Once you have started manufacturing a biosimilar medicine, it isn’t a done deal that you’ll have a successful medicine. In that respect, biosimiliars are indistinguishable from originator products.

There are also strict regulatory challenges for biosimilar medicines and regulators take time to assess and approve them. This is unlike generic medicines, which are often licensed relatively quickly and are made available to patients on much shorter timescales.

While we are seeing a fast-growing market in biosimilars in all areas, it is also becoming apparent that they might not always be commercially viable.

It has become clear from the rapid expansion of the biosimilars market, according to the QuintilesIMS European study ‘The Impact of Biosimilar Competition in Europe’, competition drives down price. The report also shows there is a relatively weak correlation between biosimilars market share and price; this is a fast-growing market that will inevitably provide complex medicines at more affordable prices, switching to biosimilar medicines may release savings in health systems that should be reinvested in patient care and not used to plug financial deficits.

We know that switching from originator projects to biosimilars is being heralded by the NHS as the next step in delivering savings to health systems, although the predicted savings on the scale suggested have yet to be delivered. Actually, it’s not switching per se but the introduction of competition, in which both the biosimilar producers and originator biologic manufacturers compete (as the IMS Health study has demonstrated). Regardless, the decision to switch should be clinically-led: considerations must be made to ensure patient access to innovative new medicines and that those are made between patients, clinicians and doctors.

There is also a burden associated with switching to biosimilar medicines both in the financial sense but also as a burden on the clinical support staff that need to manage the change. Education is a key part of these decisions. To support clinicians considering switch programmes there are a number of important documents setting out the process for clinician and patient engagement, including ‘Considerations for physicians on switching decisions regarding biosimilars’ a joint document from European Biopharmaceutical Enterprises (EBE) European Federation of Pharmaceutical Industries and Associations (EFPIA) and International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), but also on the EMA website, to show clinicians some of these toolkits available to make informed decisions about switching.

At ABPI we are working closely with our partners: the BIA, the BGMA and the BBA, as well as the regulators, to make sure that we have a sustainable and active market so that patients do actually benefit from the innovation seen in this growing field of medicines.

We continue to work closely with NHS England on a range of activities to highlight how competition within the biologics market is beneficial for patients. The ABPI recently advised on a forthcoming NHS commissioning framework document which will provide guidance to NHS commissioners about biosimilar switching programmes. We look forward to seeing the final version and hope that our industry’s insight has been considered and that the benefits to patients of an effective biosimilars market here in the UK are included.

The phenomenally complex manufacturing process involved in making biosimilars is really leading contemporary science in this field and could potentially revolutionise the treatment of some conditions.


FDA rejects Mylan and Biocon biosimilar, citing manufacturing issues

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

A biosimilar from Mylan and Biocon has been rejected by the FDA because of manufacturing issues at a production plant in India.

The companies have filed a biosimilar of Amgen’s long-lasting white blood cell booster Neulasta (pegfilgrastim) with the FDA – but the regulator has rejected it, citing issues with the manufacturing site.

In a short statement Biocon, which partners with Mylan to produce biosimilars in the US, said the filing is due to be updated with data from the facility after recent modifications required by the FDA.

The FDA’s rejection letter did not raise any technical questions, Biocon noted.

It added that it did not expect the rejection to impact on the commercial launch timing of the biosimilar in the US.

In August, Biocon withdrew filings of two biosimilars in Europe, versions of Roche’s breast cancer drug Herceptin (trastuzumab) and Neulasta, because of regulators’ concerns over the manufacturing facility in Bangalore.

EU regulators required “corrective and preventive” actions at the plant before it is able to supply drugs to the EU market.

Inspectors from France’s regulator had been conducting a pre-approval inspection of the plant, which produces biosimilars of Herceptin, Neulasta, and Sanofi’s Lantus (insulin glargine).

The FDA also raised concerns earlier this year after inspectors found a range of problems including environmental monitoring and cleaning procedures.

Neulasta has been off-patent in the US for two years this month, but is still Amgen’s second-biggest seller after its inflammatory diseases blockbuster, Enbrel.

In the second quarter sales were down 5% compared with the same period last year, to $937 million because of lower demand.


Synthetic biologists can now create novel vector constructs

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

Double Helix Technologies (Doulix) announced it will collaborate with Agilent Technologies to promote Agilent’s SureVector next-generation cloning kits through Doulix’s web platform.

Through this partnership, synthetic biologists will be able to choose among SureVector’s standard DNA parts to design custom plasmids using Doulix’s web platform.

Agilent’s SureVector is the latest innovation in next-generation cloning. SureVector harnesses the power of synthetic biology by allowing the combination of standard validated parts to create novel vector constructs.

The SureVector system enables the rapid and reliable assembly of custom plasmids for mammalian, E. coli and yeast cells by combining Agilent’s functional DNA modules with custom genes and components.

Doulix is a comprehensive toolkit for synthetic biology that allows users to easily design, validate and synthesise custom DNA vectors. Doulix combines the convenience of pre-made standard DNA parts with the freedom of a full-fledge sequence editor.

Doulix also offers a validation algorithm that allows users to review their constructs for common design flaws before proceeding to synthesis.

Davide De Lucrezia, Managing Director of Doulix, said: “Today, the unmatched flexibility of SureVector and the design capability of Doulix come together to unlock the full potential of synthetic biology.”

“This collaboration is an exciting step forward for SureVector,” said Laura Whitman, Global Synthetic Biology Product Manager for Agilent, “it allows researchers to create individual vectors and the ability to customise any fragment in the SureVector system.”

Agilent has been a leading provider of molecular biology tools since it acquired Stratagene in 2007. It is one of the few companies whose products address the entire workflow for molecular and synthetic biology.

Whitman said: “SureVector is part of Agilent’s continued commitment to providing revolutionary tools for molecular biology.”


Merck earmarks €35m for Italian biologics site development

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

Pharma firm plans new biotech production line at its Bari facility.

Merck KgAa is set to invest €35m to expand its manufacturing site in the town of Modugno, Bari in Italy, to add a new production line for aseptic filing of biologics.

Expected to be fully operational by 2022, the new production line will support the growth of the company’s biotech medicines portfolio.

Stefan Oschmann, chairman of the executive board and CEO of Merck, said: “This investment underpins the importance of the Modugno-Bari production site for our growing healthcare business.”

Modugno is one of 15 manufacturing sites in operation by Merck and the facility currently employs around 225 people.

Oschmann added: “It will help us to secure the supply of medicines that improve people’s lives around the world.”

The new production line – which is expected to pump out 14 million units per year – will be used for biologic medicines for several disease areas including multiple sclerosis, fertility and endocrinology.

The move builds on a 2014 investment made by the pharma firm that saw it inject €50m into the site for a fully automated production line using isolator technology, as well as an automated warehouse.


AbbVie adds biologic production capability to Singapore facility

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

AbbVie has expanded the operational capability of its facility located at the Tuas Biomedical Park in Singapore with the addition of a biologics manufacturing facility.

The move means the plant will now add the production of biological drugs to its repertoire in addition to small molecule active pharmaceutical ingredients (APIs).

The plant is the 13th site within the company’s global manufacturing network which spans across the US, Europe and Puerto Rico, and is the only one of its kind within the network with the capability to produce both biologics and APIs. AbbVie employs around 400 workers in Singapore, around 250 of which serve at the manufacturing plant.

Singapore’s Minister for Trade and Industry, S Iswaran, was present at the opening ceremony, where he said the facility expansion came at an “opportune moment” to meet the increasing demands of ageing populations and technological advancement.

“While these shifts will disrupt existing business models, they also present significant new opportunities,” he said.

According to Iswaran, the country’s government is committed to investing S$4 billion in health and biomedical sciences in addition to a further S$3.2 billion in advanced manufacturing and engineering as part of the Research Innovation and Enterprise (RIE) 2020 plan, a programme jointly developed by Workforce Singapore and the Singapore Economic Development Board.

“A strategic goal of RIE 2020 is to strengthen linkages between public research performers and private enterprises to create greater value from our investments in R&D,” Iswaran noted.

Over 350 people have benefitted from the programme since its inception in 2014.