AI in drug discovery: will tomorrow’s New Molecule Entities be discovered by robots?

By Valentin Fleury and Marc-Olivier Bévierre  – CEPTON Strategies

 

Artificial Intelligence (AI) is taking the old concept of “Rational Drug Design” to a new dimension. The time has not come yet where robots will replace medicinal chemists, but drug discovery in the small molecule area is on the brink of a radical transformation.

The economist Joseph DiMasi (Director of the Tufts Center for the Study of Drug Development) published a study [1] highlighting a multiplication by 6, between 1991 and 2013, of the costs of research and development engaged for a single molecule to reach the market: from ~€450m in 1991 versus ~€2,560m in 2013.

According to Deloitte’s annual report “Measuring the return from pharmaceutical innovation”, the return on investment of the big pharmaceutical companies is steadily decreasing (10% in 2010 versus 3.2% in 2017), thus predicting a possible shift in negative ROI by the beginning of the 2020 decade. This efficiency crisis shakes the traditional model of the pharmaceutical R&D to such an extent that it becomes urgent to adapt it.

 

The long and expensive way leading to drug discovery…

The research and discovery of small molecules (as opposed to biologics, which are bigger molecules, more complex, and less stable) can be seen as a succession of steps of molecules’ identification and selection. It is usually segmented into four major steps:

Figure 1 – Drug Research and Discovery steps

Lead optimisation remains a puzzle for chemists that compares to the Rubik’s cube: maximise a parameter, you will degrade another one. This step alone concentrates 20% of total research and development costs.

Next steps are more widely known to the general public: in preclinical research, the best molecules are tested on vivo models to assess their toxicity, pharmacology and pharmacokinetics. Finally, one (or more) drug candidate enters the human clinical trial phase. This is the “development” part which usually lasts several years (10 years on average, according to Bernstein Research) and accounts for 60% of total R&D costs.

Why is pharma R&D productivity declining?
The reasons for this decline in productivity are numerous and have been intensively discussed [2]. Among them, two reasons stand out, in our opinion.

First: pharmaceutical R&D addresses more complex pathological processes today than in the past. In other words, we have found medicines for all the ‘easy diseases’, and we are now facing the “difficult” ones.

The second reason is based on a technological bias: the scientific and technical progress of the 80s and 90s allowed the industrialisation of certain research stages. For instance, High Throughput Screening (HTS) or more recently DNA-encoded chemical libraries have artificially inflated the number of leads generated, by increasing the capacity of the filtration stages, without increasing their quality in similar proportion. Thus, more molecules, not better ones, have been pushed through later stages of development, generating more spending without better results in the end.

Thus, the pharmaceutical industry is now seeking to reduce operational costs and improve cycle time within research and development. And AI’s ability to reduce drug development times is increasingly established.

The potential of AI in drug discovery

To improve productivity in small molecule discovery, the key challenge is to find a molecule (the identification part of the process) that maximizes a large number of very diverse criteria, which will be tested sequentially, one after the other (the selection part). Artificial Intelligence (AI) makes it possible to build holistic models for the design of new drugs where these tests can be performed simultaneously, in silico.

The use of deep learning algorithms in drug discovery became widespread in 2012, after Georges Dalh won the Merck Molecular Activity Challenge by demonstrating the effectiveness of little trained deep neural networks to predict the activity of a molecule starting from its structure [3]. This has automated a discipline well known to chemists: QSAR (Quantitative Structure-Activity Relationship).

In 2016, in an article entitled “Automatic chemical design using a data-driven continuous representation of molecules“, Alan Aspuru-Guzik et al.[4] describe a method of continuous and multidimensional representation of the chemical space using deep neural networks. This method allows a simpler, faster and more comprehensive exploration of the chemical space (estimated at 1060 molecules potentially usable as a drug), and ultimately, the generation of virtual molecules previously inaccessible even via the largest databases (containing about 108 molecules).

A case study…

One of our clients, IKTOS, a French start-up founded in 2016, has developed an AI technology capable of generating molecules under the constraint of a set of physicochemical and biological characteristics, according to in silico predictive models of such characteristics.

IKTOS technology is based on the interweaving of three algorithms, which are orchestrated to enable an efficient exploration of the chemical space in an iterative manner and enable the identification of optimal in silico compounds in a few hours of computation.

The first is a generative model: trained on databases containing several million chemical compounds, it can “build” virtual molecules located anywhere in the chemical space (implementing a principle close to that proposed by Gomez-Bombarelli et al.).

The second is a predictive algorithm: trained on a customer database that contains already available and tested molecules, those models can predict the physicochemical and pharmacological properties of a molecule only from its chemical structure.

The third is the reinforcement algorithm: the reinforcement component uses the information (scores) provided by the predicted models on the previous sets of generated molecules to modify the weights of the generative model in order to orientate the molecule generation in the right direction.

This technology has demonstrated[5] its effectiveness through a collaboration with a major pharmaceutical company. For 10 years, the chemist team had tried to make compounds maximising a set of 11 biological activity criteria. Among the 900 compounds that they had synthesized and tested; they were not able to find any molecule hitting more than 9/11 success criteria. In just a few days, IKTOS technology generated 150 virtual molecules which were predicted to meet all 11 criteria, in silico. Out of those 150 molecules, 11 were selected (based on their synthetic accessibility and originality), synthesized by the chemists, and tested on all 11 criteria. 9 molecules were found to maximize 9 criteria, 3 to maximize ten criteria, and 1 molecule was found to be good on all 11 success criteria. It took only a few days for an AI, and 11 molecules, to achieve better results than what had been achieved by a team of chemist experts over 10 years of benchtop research and 900 trials of molecules.

An emerging field attracting massive investments

The use of artificial intelligence in small molecule research is quite new, and it is still difficult to figure out how far it will go. We have identified -and often met as well- more than a hundred companies (mainly start-ups) at the crossroad of pharmaceutical R&D and AI. Many start-ups are flaunting attractive technologies, but those who are really able to deliver high value-added and actionable results are still few in number. In addition, the still limited number of success stories and the confidentiality that surrounds most of them contribute to a lack of clarity among medicinal chemists around the applications of AI in their profession. In fact, big pharma is still seeking to understand the possible applications of AI, and to evaluate existing technologies and stakeholders.

Numerous partnerships have been signed recently, demonstrating the growing interest in the area (Sanofi with Exscientia and Recursion, Merck with Atomwise, GSK with Cloud pharmaceuticals, InSilico Medicine and Exscientia, Iktos and Janssen, Iktos and Merck). The increasing number of scientific publications in recent years also reflects the enthusiasm of the scientific community and the industry. In addition, private investments are accelerating (~$30m invested in 2012 versus ~$500m and ~$800m in 2014 and 2016 respectively). The enthusiasm of investors is all the greater when certain start-ups, initially service providers of R&D for the pharmaceutical industry, develop their own pipeline of molecules and thus compete frontally with traditional biotech startups. Benevolent AI, whose first clinical trials on Parkinson’s disease began in 2018, holds 20 molecules in the preclinical phase, and has recently raised $115m. Today, it is valued at $2bn.

Towards automated drug discovery?

Certain companies (like SRI or Catapult Medicine Discovery) aim at developing a fully automated research workflow, from automated design and retrosynthesis to robotised synthesis and tests. We are not among the few utopians who believe in the total automation of pharmaceutical drug discovery. Nevertheless, AI will certainly contribute to deeply transforming pharmaceutical research. As some say, “AI will not replace medicinal chemists, but medicinal chemists who use AI will replace those who don’t”. Investments of pharmaceutical companies in AI are nibbling budgets of benchtop research and computational chemistry, progressively driving research activities to more in silico and automated methods. Today, most of the major names in the industry develop partnerships with companies mastering these technologies. The question remains whether they will try to internalise it or not. If not, we expect to see in the next few years the emergence of a new model of AI-based biotech start-ups, with highly automated discovery processes, and sufficient funding to develop their own pipeline.

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Sources:
[1] DiMasi JA, Grabowski HG, Hansen RA. “Innovation in the pharmaceutical industry: new estimates of R&D costs”. Journal of Health Economics 2016
[2] J.W. Scannel et al. “Diagnosing the decline in pharmaceutical R&D efficiency”. Nature 2012
[3] George E. Dahl et al. “Deep Neural Nets as a Method for Quantitative Structure-Activity Relationships”. Journal of Chemical Information and Modeling 2015
[4] Alan Aspuru-Guzik et al. « Automatic Chemical Design Using a Data-Driven Continuous Representation of Molecules”. ACS Central Science 2018
[5] “Deep Learning For Ligand-Based De Novo Design In Lead Optimization: A Real Life Case Study”. Iktos and Servier Poster 2018

The growing role of Real-World Evidence, from regulatory strategies to patient management

By Alexandre Bréant and Marc-Olivier Bévierre CEPTON Strategies

The excitement and controversies that ensued the presentation of the Apple Heart Study at the AAC congress earlier in March show how data generation is evolving in the pharma industry: health data, coming from a non-medical device, harvested by a non-medical company.

How can Real-World data and Real-world Evidence be integrated in pharma companies’ best practice and help them redefine what standard of care means for the medical community and the patients?

Summary

Real-world evidence (RWE) is the evidence derived from real-world data (RWD), which is any kind of health-related data not coming from a clinical trial. Far from opposing to one another, real-world data and data from clinical trials complement each other. Together, they could reduce time to market of innovative solutions, help both the payer and the industry derive better value from treatments, inform clinical practice and optimize treatment allocation to the patients most-likely to have the highest benefit/risk ratio.
However, to realize the full potential of RWD, changes need to happen in both the public (regulatory, payers, healthcare infrastructure) and private side to define the data standards as well as the best practice to collect, consolidate, present and use these data.
With no doubt, companies integrating RWE at each step of the value chain will gain a competitive advantage but this requires an in-depth change in the way data are strategically considered and operationally collected, managed and analyzed.

Introduction

Sometimes, there is merit in comparing apples with oranges. Or more accurately a quart of cider vs. two oranges and a lemon daily, as did James Lind when searched for a cure to scurvy in 1747. Scurvy is a disease resulting from lack of vitamin C that plagued sailors during the Age of Sail. Lind took 12 scorbutic sailors, with “cases as similar as [he] could have them” and split them into 6 groups of 2, gave each group a different treatment (cider, citrus fruits, vinegar, elixir vitriol or mere sea water) and compared the health improvement in each group. This experiment is considered as the first controlled clinical trial [i] and since then, the methods for clinical trials have been refined and improved (blinding of patients and health-care providers, randomization and stratification, advanced statistical analysis, reporting guidelines…) to reach what is now considered the gold standard of evidence generation and the foundation of evidence-based medicine: the double-blind, randomized controlled trial (RCT).

However, while RCT’s praised methodology reduces the risk of getting false positive or false negative results, it does so at the expense of its generalizability to a broader population of patients: for a given treatment, efficacy could substantially differ from effectiveness, as nicely illustrated in the British Medical Journal [ii]. Indeed, efficacy is measured under almost ideal conditions on a carefully selected population in an RCT while effectiveness is evaluated in conditions of clinical practice on the more variable population of patients that exist in real-life.

In an ideal world, data should combine the richness of the real-world setting with the objectiveness of the clinical trial setting. With the increased digitization of the world [iii], will real-world data be able to fulfill this ambitious objective?

 

What are real-world data and real-world evidence?

As defined by the Innovative Medicine Initiative (IMI), Real-World Data (RWD) are “An umbrella term for data regarding the effects of health interventions (e.g. safety, effectiveness, resource use, etc) that are not collected in the context of highly-controlled RCT’s”. Real-world Evidence (RWE) is the evidence derived from the analysis and/or synthesis of RWD.

This definition makes it obvious that RWD and data from RCT are complementary subsets of the overall health data available. RWD can come from several sources and be split in 3 different types (see Box 1).

How can RWE be used?

RWD is, fundamentally, data, which means they could be useful, in principle, anywhere data coming from RCT are currently used (regulatory decision for marketing authorization, HTA evaluation for pricing and reimbursement, guideline elaboration and treatment decisions) and even beyond, as it could help empowering the patients.

Regulatory

The primary concern of the regulator is the evaluation of the benefit risk ratio throughout the product lifecycle, so they welcome any reliable information that improves their assessment. Therefore, the EMA considers that, for regulatory purposes “leveraging RWE is a need – and an achievable goal”[vii]. For example, RWE could be used in evidence generation:

– Before marketing authorization (i.e. to obtain new indication or expand indications):

  • To demonstrate efficacy (e.g. External control for very rare conditions, complement or even replace RCT [viii] in some cases)
  • To enrich safety data

– After marketing authorization:

  • For post-approval Efficacy [1] or Safety Studies (PAES/PASS)
  • For Effectiveness [2] demonstration

For example, today, home hemodialysis (HHD) is a treatment reserved for young and autonomous Chronic Kidney Disease (CKD) patients. However, most nephrologists believe that with smart telemonitoring services HHD could safely be extended to sicker patients (older and/or with comorbidities). In this case, the generation and analysis of RWD on compliance (number and duration of dialysis sessions), efficacy (ultrafiltration rate), and safety (vascular access state) would allow both nephrologists and patients to safely consider HHD as a relevant dialysis modality.

Market access

Payers aim at maximizing public health within the constraints of their budget. This mandate is becoming increasingly difficult with the high price of innovative treatments and the ongoing demographic mutation of developed economies (rise of chronic diseases, increased proportion of senior citizens…).

To optimize spending, they more and more often rely on managed entry agreements (MEA) with pharmaceutical companies, such as value-based pricing or outcome-based contracts. The idea behind the MEA is simple: if a certain level of effectiveness is not met by a predefined deadline, the pharmaceutical company should reimburse all or some of the treatment for that patient.

For example, in 2015 Janssen agreed on rebates on Olysio to the NHS if the patient is not cured within 12 weeks [ix]. To limit the likelihood of a failure (and a rebate), Janssen provided a companion blood test to help predict whether a patient would respond to the treatment, thus limiting the number of patient’s futile exposure to a serious and expensive treatment. Real-world evidence can also be used for pay-for-performance schemes when the situation is not as black and white as the Olysio case, where the cure is the expected outcome. In 2007, a pay-for-performance scheme was negotiated between Janssen and the NHS for Velcade in multiple myeloma. In this scheme, “the company will provide replacement stock or credit for those patients at first relapse who fail to respond to Velcade”, response being measured as the reduction of at least 25% of a serum biomarker [x]. With this response-based rule, Velcade became cost-effective despite their high then-price and was granted reimbursement.

Clinical practice

Improved access to RWE could also mean a continuous and hyperlocal analysis of data, which could guide treatment decision on what works best on specific patient populations:

  • Taking into account the geographical, social and personal components [xi] to select a given treatment course or sequence (RWE were cited as the most important data to inform treatment decision, before RCT data, in a recent survey [xii])
  • Identify subpopulations or relevant biomarkers [xiii]
  • Improve original drug schedule to improve efficacy and or adverse event management [xiv]

Patient empowerment

Whether it is through the extension of available indications, a better reimbursement or improved care, Real-world evidence generated from Real-world data are ultimately benefiting the patients. However, on the patient side, the mere production of RWD could also be beneficial, as the involvement of the patients in their care boosts adherence and helps detect complications and signs of relapse in real-time, to avoid wasting precious time at critical moments. For example, symptom monitoring through an online portal not only improves quality of life, patient satisfaction and ER utilization but also has a significant impact on extending patient’s overall survival [xv].

 

What are the key issues and opportunities for companies willing to use real-world data?

The EU has started funding many initiatives to bolster the generalization of RWD and RWE, and the EMA is strongly advocating for their use on a routine basis. However, Pharma companies should also marshal their resources to ensure they can seize the opportunity to improve their practice at every steps of their operations:

– Improve clinical trials through:

  • Better understanding of patients and medical community needs
  • Combining traditional RCTs, adaptative trials, pragmatic trials and collect data from more sources
  • Pooling data from several trials to speed up trial execution and reduce unnecessary patient exposure

– Enrich Payer value proposition:

  • Narrow the gap between efficacy and effectiveness
  • Track the actual economic value of their treatments or of their competitors

– Isolate better responding population through biomarkers or socio-economic data

– Engage with patients in a compliant fashion, to better gather feedback and maximize treatment benefit

We see 3 key topics to be addressed by companies willing to build expertise in RWD:

1.      Technical

Real-world data are rarely as clean as RCT data, since RCT data is homogenous, recorded in controlled conditions on well-defined patients, with identified confounding factors and strategies to minimize their influence. This implies several technical challenges to collect RWD in a timely and standardized manner despite the variability of the points of care, store them properly, especially within the framework of GDPR in Europe.

2.      Talent

Parallel to the technical challenges mentioned above, analyzing RWD is more complicated than designing a priori a robust statistical analysis plan. It requires expert data scientist profiles, combining strong biostatistics knowledge and IT acumen to exploit the data lakes of structured and unstructured data of uneven quality.Beyond pure technical profiles, a new breed of cross-functional coordinators will be needed to ensure smooth information flow and alignment between all internal (R&D, Medical affairs, Regulatory affairs, Market Access, Patient centricity, Public affairs, IT, BI and analytics, Legal…) and external stakeholders (Regulators, Payers, Scientific and patient organizations, Insurers, Hospitals, …).

3.      Governance

The importance of the coordinator position will go hand in hand with profound changes in governance, especially regarding the strategic role of these data on how to prioritize assets, to decide on the focus of future acquisitions or in-licensing. The questions of “who owns the data”, “what can be done with it” will be central in the generation and use of RWE, which will not accommodate the frequent siloed ways of working still at play in many pharma companies.

 

Conclusion

Far from opposing to one another, real-world data and data from clinical trial complement each other. Together, they could reduce time to market of innovative solutions, help both the payer and the industry derive better value from the treatments, inform clinical practice and optimize treatment allocation to the patients most-likely to have the highest benefit/risk ratio. However, to realize the full potential of RWD, changes need to happen in both the public (regulatory, payers, healthcare infrastructure) and private side to define the data standards as well as the best practice to collect, consolidate, present and use these data. With no doubt, companies integrating RWE at each step of the value chain will gain a competitive advantage but this requires an in-depth change in the way data are strategically considered and operationally collected, managed and analyzed.[1] Efficacy: benefits measured in a RCT setting[2] Effectiveness: benefits measured in clinical practice

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Sources :

[i] A. Bhatt, Perspect Clin Res. 2010 Jan-Mar; 1(1): 6–10.

[ii] Yeh et al. BMJ 2018;363:k5094

[iii] https://www.politico.eu/sponsored-content/making-the-eus-health-systems-fit-for-the-21st-century/, consulted March 12, 2019

[iv] Eichler et al, Clinical trials 2018 Vol 15 (S1) 27-32

[v] https://edps.europa.eu/data-protection/our-work/subjects/health_en consulted March 12, 2019

[vi] https://arstechnica.com/gadgets/2018/10/amazon-patents-alexa-tech-to-tell-if-youre-sick-depressed-and-sell-you-meds/ consulted March 12, 2019

[vii] Eichler, Real-World Evidence – an introduction; how is it relevant for the medicines regulatory system, EMA, London, April 2018

[viii] https://www.fdli.org/2018/08/update-fdas-historical-use-of-real-world-evidence/, consulted March 13, 2019

[ix] https://www.fiercepharma.com/pharma/janssen-agrees-to-rebate-cost-of-olysio-to-england-s-nhs-if-it-doesn-t-work consulted March 12, 2019

[x] https://www.nice.org.uk/guidance/ta129/documents/department-of-health-summary-of-responder-scheme2

[xi] https://www.medscape.com/viewarticle/910447, consulted March 16,2019

[xii] http://www.volumetovaluestudy.com/docs/Tracking%20the%20Shift%20From%20Volume%20to%20Value%20in%20Healthcare.pdf, consulted March 13, 2019

[xiii] Fiore et al. Clin Pharmacol Ther. 2017;101(5):586-589.

[xiv] Boegemann et al. Anticancer Research November 2018 vol. 38 no. 11 6413-6422

[xv] https://meetinglibrary.asco.org/record/147027/abstract, consulted March 13, 2019

Forever young: how the cult of beauty created a $11bn medical aesthetics market

By Maxime Huerre and Francis Turina-Malard, CEPTON Strategies

 

Looking younger, fitter, and correcting body imperfections: these are the pillars that have been driving the insatiable demand for aesthetic procedures and sustaining the market dynamism over the past few years. In quest for treatments always more “natural” and safer, patients have been increasingly seduced by non-invasive procedures that recently emerged on the market. Formerly reserved to a wealthy population, these less invasive practices and technologies have driven the democratisation of aesthetic medicine toward a younger and broader public. Meeting this demand and diversifying their offer, aesthetic players benefited from a significant and unstoppable growth. But what are the key activities behind such a success?

 

The Medical Aesthetics, a $11bn market dominated by the US

The International Society of Aesthetic and Plastic Surgery (ISAPS) registered circa 23 million surgical and non-surgical aesthetic procedures worldwide in 2017, for a total medical aesthetics market value estimated at circa $11bn.

From heavy surgeries, such as breast and buttock implants, to less invasive procedures, such as injections or laser-assisted treatments, the demand for aesthetic procedures has been steadily growing over the past few years.

The medical aesthetics market can be divided in four segments:

Figure 1 – Medical Aesthetic market segmentation

 

Over-represented due to higher prices, the US represents twice the European market, and 50% of the global market value. In Asia, the unformal and hidden practice of aesthetic procedures represents a major obstacle to faithfully measure the demand. Nonetheless, Asia is estimated to represent 20% of the global market and to be the most dynamic geography.

Figure 2 – Market breakdown of medical aesthetics by geography

Facial aesthetics driving the market

A. Facial aesthetics is the largest and well-established segment (half of the global market in value). It is dominated by three generalist companies (Allergan, Galderma and Merz) that have established their positioning through the development of several generations of injectables, from collagen to botox and hyaluronic acid. These products are used for wrinkle correction, facial tissue augmentation and lip enhancement. They are injected by plastic surgeons and dermatologists.

B. Unlike injectables, energy-based devices can be used in various distribution locations such as aesthetic centres, gynaecologists or spas. The broader and easier access to this technology makes it a serious alternative to injections and surgical procedures. Moreover, the complete non-invasive aspect of some energy-based products is an argument to convince patients mistrustful of injectable products and concerned by health hazards of aesthetic products. Nevertheless, energy-based devices have a limited scope of action, mostly skin stimulation functions.

C. Skin tightening and body contouring devices aim to remove body fat excess which cannot be eliminated through natural methods such as exercise or specific diets. Liposuction, the traditional method, is an invasive and painful procedure associated with risks of bleeding, infection or embolism. To limit adverse events, non-surgical treatments have been recently developed and are gaining popularity. For instance, several technologies such as cryolipolysis, laser lipolysis or radiofrequency lipolysis target and naturally eliminate fat cells by using controlled freezing or heating. These technologies cannot be considered as weight loss solutions but can effectively remove stubborn fat excess. Among the invasive procedures, the transfer of autologous fat from an unwanted area to a desired one, called “Brazilian Butt Lift”, has also been experiencing a dynamic 10% growth in 2017.

D. Despite frequent health and sanitary scandals, aesthetic surgical implants are still a growing market. Breast augmentation remain the top surgical procedure, but their number has been stagnating while buttock augmentation is driving this segment growth. The recent international “Implant files” scandal published in November 2018 highlighted severe failures in medical devices monitoring and could act as an impediment to this segment sustainability.

Strong underlying drivers fuelling a sustainable growth

Growing at around 8% per year, the medical aesthetics market is certainly one of the most dynamic markets among the different healthcare specialties. This growth is fuelled by several strong factors.

First, demographic trends steadily contribute to the aesthetic market growth. The worldwide population is continuously growing at +1% per year until 2025 thus logically increasing the target population. Furthermore, the ageing population (over 60 years old) is expected to grow at +3% per year until 2025.

In addition to demographic factors, several societal changes raise the promise of expanding the target population in medical aesthetics.

The first trend is the rising demand for safer, more natural and less invasive aesthetic procedures. In this context, non-surgical procedures have gained popularity and have emerged as a standard transition step between cosmetics and surgery. They largely contributed to the growth of the global aesthetics market and gained momentum over surgical procedures. For instance, in Japan, Brazil and Europe non-surgical procedures have significantly gained market share on the overall number of surgical procedures (see figure 3).

Figure 3 – Penetration of non-surgical procedures in the medical aesthetic market (source: ISAPS Global Statistics 2010, 2016)

On the other hand, women, but also men, are eager to engage in aesthetics procedures younger than ever. Aesthetic doctors and private companies have rapidly adapted to this untapped reserve of patients by luring these new profiles with “beautification techniques”, such as innovative dermal fillers and skin boosting technologies. Convinced by the reversible effects of these products, this younger population has appeared as a new, large, and promising source of growth for medical aesthetics players.

In Asia, beauty standards prove to be slightly different from the ones in the US and Europe. Patients are either looking for skin pigmentation control solutions or for lip/cheek augmentation. As this second trend requires high injection volumes, it has dramatically fuelled the demand for dermal fillers.

 

Four technologies of injectables: substitutable or complementary?

In addition to traditional promotional campaigns, celebrities and reality TV stars have largely contributed to promoting the use of injectables, particularly among a younger population. But what are the different products on this market and how do they differentiate themselves?

Collagen, the deceased market leader

First dermal filler to be approved by the FDA in 1981, collagen from bovine origin has long been used for regenerating volumes and filling lines in facial aesthetics. Because of Collagen injection site reactions, the lack of antidote and the emergence of more efficient products, collagen has progressively lost momentum. The production of a recombinant collagen at a low cost could reverse that trend but the current state of research is not ready to propose a comeback in the next 10 years.

Botox, the well-established market leader

Botulinum Toxin, commonly called Botox, is produced from the bacteria Clostridium Botulinum. As a neurotoxin, Botox can be considered as a poison for the body due to its potential harmful effects on the nervous system. However, when administered correctly in dermal fillers, it is used to remove wrinkles thanks to its paralyzing function on the targeted muscles. Treatment effect lasts around 4 to 6 months and injection must be repeated to preserve the effects.

Over the past 10 years, Botox has been maintaining its dominant position in facial injections, with a global growth of +5% per year, and globally resisting to competition from other dermal fillers. It is the first non-surgical procedure, representing 59% of all injection procedures performed in 2017.

Hyaluronic Acid (HA), the unstoppable challenger

Hyaluronic Acid is a biopolymer naturally present in the human body (around 15g per human body). HA was originally extracted from rooster combs but is now largely obtained from bacteria bio fermentation. Thanks to its capacity to absorb massive quantity of water, HA can be transformed into a gel with viscoelasticity and moisturising properties (see figure 4). As a natural and friendly compound, HA, contrary to Botox, benefits from a very positive perception from the public.

Depending on the transformation process, HA can be either used as a dermal filler to remove wrinkles (cross-linked HA) or as a skin-booster (linear HA). Treatment effect lasts between 3 months (linear HA) and 12 months (cross linked HA). HA has steadily penetrated the market and is now representing 38% of injection procedures (2017). In Europe, HA is even standing shoulder to shoulder with Botox while in the US, Botox succeeded in preserving its leading position so far.

Figure 4 – Transformation chain of HA (source: Cepton Analysis)


Platelet-Rich Plasma (PRP), the new comer

Platelet-Rich Plasma is a concentrate of platelets in plasma free of red blood cells. PRP injections, prepared from the centrifugation of the patient’s own blood to separate the platelets, are used for facial rejuvenation purposes and against hair loss. PRP aims to repair and regenerate the quality of the patient’s skin. The stimulation of growth factors contained in platelets activates the “healing process” of aged tissues and conducts to a “regeneration effect”.

The media coverage, under the name of “Vampire Lift”, largely participates in promoting these therapies. However, considering the time (30 minutes), the expertise and the equipment required to prepare the injectable, barriers remain high to the penetration of PRP over other existing and well-established technologies.

 

Figure 5 – Injection sites of different technologies of injectables

Although all these technologies are used as stand-alone injectables, most of them coexist and can even be associated. First, PRP plays a different role and does not have the required filling properties to be used for wrinkles removing. PRP and HA can therefore be combined to provide enhanced anti-aging skin properties: HA would provide the volume corrections and PRP the skin rejuvenation. Second, products such as Botox and HA have different injection sites, which makes these technologies complementary.

Clear skies for the medical aesthetics market

As a conclusion, the medical aesthetics industry is a continuously-growing market with very few hurdles, apart from health and sanitary hazards. Injectables being now classified as Class III medical devices in the European regulation, the increase in regulatory requirements is likely to raise new market hurdles for smaller players and to lead to further market consolidation.

It certainly remains one of the most profitable industries with significant margins at each step of the value chain: manufacturers, distributors and physicians. The search for more “natural”, body-friendly, and safer practices being today’s opportunity to capitalize on.

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Sources:

The History of Injectable Facial Fillers, T. Kontis and A. Rivkin, 2009

Global Statistics from the International Society of Aesthetic Plastic Surgery (ISAPS), 2010-2017

Reports on the Emerging Trends in Aesthetic Medicine in 2018, International Association for Physicians in Aesthetic Medicine, 2018

CEPTON ranked among the top consulting firms in Healthcare and Pharma Industry by the magazine “Les Décideurs”

For the second consecutive year, CEPTON has been ranked in the highest category of consulting firms in Healthcare by the French leading business magazine “Les Décideurs” (2018). Twelve years after its creation, this is a wonderful recognition for all our team, and this is a great trust from our clients all along these years.

Décideurs 2018 study

Lien :
https://www.magazine-decideurs.com/classements/strategie-organisation-management-secteur-sante-industrie-pharmaceutique-classements-2018-cabinet-de-conseils-france

CEPTON ranks among the best consulting firms in France in categories “Strategy” and “Healthcare”.

The CEPTON team is proud to announce that, after only 10 years of existence, CEPTON has already been ranked among the best consulting firms in both categories “Strategy” and “Healthcare”, beside large international consultancies, according to an independent study performed by the business magazine CAPITAL in October 2016, where more than 4000 executives have been interviewed.

Links:

Ranking by industry,

Ranking by expertise.

Philippe COCUDE joins CEPTON

Our consultancy firm’s publication | CEPTON Strategies

We have the pleasure to announce that Philippe Cocude joins CEPTON as a new partner in the Paris office. Philippe has over 25 years of experience advising companies and investors in Healthcare, including pharmaceuticals, Medical Devices, Animal Health, Diagnostics (both human and environmental), Nutraceutics, Dermo-cosmetics, and Medical Services.
Prior to CEPTON, he was the founder and Managing Partner of AEC Partners, a management Consultancy focused on Healthcare, Based in Paris and New York. He has also been the CEO of a privately-owned pharma company, a consultant at Arthur D. Little and at Groupe ABC. He started his career at Banque Paribas.
“CEPTON in specialized in Healthcare and relies on very experienced teams. I think this is the right consulting model for today’s times of changes in the healthcare industry.”, says Philippe Cocude.
CEPTON is a European-style strategy boutique founded by Jean Reboullet in 2006. CEPTON’s partners have all served in large, international consultancies (BCG, Roland Berger, ADL, Booz & Co) or in global pharmaceutical corporations (Novartis, Johnson & Johnson). Since its inception, CEPTON has put a strong focus on Healthcare and relies on experienced teams that are able to quickly bring value to their clients on complex, critical business issues. “I am very happy to welcome Philippe in our team of Partners. His experience and know-how in healthcare is unmatched in France.”, said Jean Reboullet.

Towards a more integrated approach of patient care (Le Monde)

Article in the Press about our consultancy firm

Le Monde, Marc-Olivier Bévierre
The French National Health Service is looking for more quality, but also more efficiency in the delivery of care. Everyone agrees now that integrated care will be a source of huge savings and therefore is one of the keys of the long-term survival of the French healthcare system.
However, implementing integrated care on a national scale is not an easy task in a context where the only payer and healthcare operator is the Government.

CEPTON supports the development of biotech in France

Article in the Press about our consultancy firm

Biotech/Medtech companies are a major source of value and job creation in France. Moreover, they need more and more engineers and offer them interesting career opportunities XMP-Biotech, (Association of Ecole Polytechnique/PartisTech Alumni working in biotechs and biopharma companies), organized on march 17th a conference to show the industry’s achievements and outlook.This conference was sponsored by PIERRE FABRE and CEPTON strategies, a European consultancy specialized in healthcare.

Hepatitis C: the future landscape

Our consultancy firm’s publication | CEPTON Strategies

New breakthrough treatments of Hepatitis C are emerging, which are considerably more effective and lead to complete remission in more than 90% of cases. This raises the hope is that the disease may be eradicated within the next 10-15 years. Who will be tomorrow’s leaders in this market? CEPTON has analyzed the pipelines of key players and the outlook of this promising market.

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Molecular diagnostics: market dynamics and future developments

Our consultancy firm’s publication | CEPTON Strategies

Colloque France Biotech, le 7 juin 2012. Molecular diagnostics is the key to personalized medicine. In that respect, it has a promising future. However, the regulatory and market access landscapes are still fragmented and lack a clear framework. Many barriers still remain today. CEPTON has spoken at France Biotech’s congress on this topic in Paris, on June 7, 2012.

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The Revolution of personalized medicine

Our consultancy firm’s publication | CEPTON Strategies

From risk profiling to gene therapy and molecular diagnostics, personalized medicine opens new, exciting fields to medical research. Not only is it good news for the patients: considerable improvements are at stake, both for health systems and pharmaceutical firms now struggling to reinvent themselves. But the road ahead is still full of obstacles.

The concept of personalized medicine was introduced two decades ago by the Swiss company Roche. The initial concept was based on a simple reality in medical practice: the same drug may induce different reactions according to patients, and for a given patient, some drugs work while others don’t.

With the introduction of a treatment of breast cancer in the 1990’s, Roche demonstrated that it was possible to anticipate which patients would or would not benefit from the treatment.

It became therefore possible to personalize treatments, that is to administer a drug only to those patients who would react positively to it. The impact of this new approach is huge: a better efficiency, less side-effects, and no more waste of time and resources spent on a treatment that does not work.

Read the full article on Paristechreview.com