L’IA dans la découverte de médicaments: les robots découvriront-ils les entités moléculaires nouvelles de demain ? (article en anglais)

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.


[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

L’importance croissante des Données en Vie Réelle, des stratégies réglementaires à la gestion du patient (article en anglais)

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?


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.


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.


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.



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


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

A jamais jeunes: comment le culte de la beauté a créé un marché de la médecine esthétique à $11Md (article en anglais)

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 (sources: Cepton analysis based on various market studies)

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: substituable 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 niche competitor

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. Dermal fillers being now classified as Class III injectable 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.



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 parmi les cabinets de conseil incontournables en Santé et Industrie Pharma selon le magazine “Les Décideurs”

Pour la deuxième année consécutive, l’étude publiée par le magazine “Les Décideurs” classe CEPTON parmi les meilleurs cabinets de conseil en Santé et Industrie Pharmaceutique (2018). Douze ans après la création du cabinet, c’est une formidable reconnaissance pour le travail et les efforts de notre équipe.

Décideurs 2018 ranking

Lien :

CEPTON classé par la magazine “Capital” parmi les meilleurs cabinets de conseil dans les catégories “Stratégie” et “Santé”.

Après seulement 10 ans d’existence, CEPTON vient déjà d’être classé parmi les meilleurs cabinets de conseil dans les catégories “Stratégie” et “Santé”, selon l’enquête indépendante du magazine CAPITAL parue en octobre 2016, qui a interrogé plus de 4000 personnalités du monde des affaires en France. Tout l’équipe de CEPTON est très fière de cette reconnaissance qui consacre dix ans d’efforts soutenus et nous positionne désormais au côtés des plus grands cabinets internationaux.

Liens :

Classement des cabinets de conseil par secteur,

Classement des cabinets de conseil par spécialité.

Pharma 2015 : une nouvelle approche de l’hôpital

L’hôpital, au centre du système de santé, concentre de plus en plus l’attention des industriels.
Mais aujourd’hui, les besoins changent, et les laboratoires doivent s’adapter. Une nouvelle approche commerciale des hôpitaux est nécessaire, plus collaborative et plus globale. L’industrie pharmaceutique doit adopter les approches de type “Key Account Management”, déjà largement répandues dans d’autres industries telles que l’automobile ou la chimie.

L’industrie alimentaire au service de la santé : un rêve en pleine croissance

Le marché de «l’alimentation santé» est très dynamique. Et même si la science nutritionnelle est complexe, sa croissance ne semble pas près de s’interrompre, analysent dans cette tribune l’hépato-gastroentérologue et consultant associé à The Family Jean-David Zeitoun et Marc-Olivier Bévierre, directeur associé de Cepton Strategies.

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Philippe COCUDE rejoint CEPTON

Nous avons le plaisir d’annoncer l’arrivée de Philippe Cocude comme nouvel associé chez CEPTON. Philippe est diplômé d’HEC Paris. Il a plus de 25 ans d’expérience de Conseil et de Direction Générale dans la Santé : Pharmacie, Santé animale, Dispositif médical, Diagnostique, Cosmétique, Services à la personne….
Avant de rejoindre Cepton Strategies, Philippe a été le fondateur et le Managing Partner de AEC Partners, il a aussi été Directeur Général du laboratoire Innothera et auparavant Consultant en stratégie chez Arthur D.Little et ABC Groupe. En complément de son activité professionnelle et pendant plus de 15 ans, Philippe a été chargé de cours de finance à HEC Paris.
“Le modèle de CEPTON, spécialisé dans l’univers de la santé et reposant sur des équipes très expérimentées, m’a séduit car il correspond bien aux besoins de cette industrie en pleine mutation”, déclare Philippe Cocude.

CEPTON est un cabinet de conseil de Direction Générale créé en 2006 par Jean Reboullet, dont les associés sont issus de grands cabinets de conseil internationaux (BCG, Roland Berger, Booz) ou de grands groupes pharmaceutiques (Novartis, Johnson & Johnson). Dès le départ, CEPTON a misé sur l’expérience et la spécialisation de ses équipes, ce qui leur permet de monter rapidement en puissance sur des sujets complexes et à fort impact pour ses clients. “Je suis très heureux d’accueillir Philippe comme nouvel associé chez CEPTON, car il nous apporte une expérience et un savoir faire inégalé en France dans l’univers des industries de santé.”, déclare Jean Reboullet.

Mieux gérer le parcours du patient est un impératif (Le Monde)

Marc-Olivier Bévierre, Le Monde En quête d’une plus grande qualité des soins mais aussi d’économies, les autorités de santé s’intéressent de plus en plus à “l’avant” et “l’après”. Autrefois, on allait chez le médecin lorsqu’on était malade, on repartait avec un traitement et on espérait être tranquille le plus longtemps possible! On voit aujourd’hui les limites de cette approche, et on s’est rendu compte qu’intervenir en amont (dépister, intervenir dès les premiers signes de la maladie) mais aussi en aval (adapter les traitements, prévenir les rechutes) est souvent bien plus important, plus efficace, et plus économique.

“Mieux vaut prévenir que guérir”, dit l’adage, qui ne croit pas si bien dire. Dans le diabète par exemple, on sait que le suivi rigoureux et régulier du taux de glycémie est fondamental pour la survie du patient et pour son état de santé général. En psychiatrie, le taux d’hospitalisation est divisé par deux si le patient prend son traitement régulièrement et si on l’aide à anticiper ses crises.

Les même principes s’appliquent dans toutes les maladies chroniques: asthme, hypertension, sclérose en plaques, cancer,… Tout le monde s’accorde aujourd’hui pour dire que la bonne gestion du parcours de soins est une des clés de la qualité des soins, mais aussi de la pérennité de notre système de santé.

Facile à dire, mais pas forcément très simple à réaliser en pratique, car de nombreuses questions se posent: comment partage-t-on les données de santé du patient, qui y a accès? Qui est en charge de la coordination globale du parcours de soins et comment se fait-il rémunérer pour cela? Dans les pays où ce sont des assureurs privés qui payent, ces questions-là ont trouvé des réponses depuis longtemps. En France, notre Sécurité Sociale, qui autrefois remboursait tout sans discuter, a maintenant compris que c’est là que résidait une des clés de sa survie… Reste maintenant à mettre en œuvre les solutions à grande échelle.

CEPTON soutient le développement des biotechnologies en France

Les entreprises de biotechnologies, portées de plus en plus par des ingénieurs à la formation généraliste, offrent des perspectives de croissance et d’emploi majeures en France A l’occasion de ses 10 ans, XMP-Biotech, (association des ingénieurs de Polytechnique, de l’Ecole des Mines et de ParisTech travaillant dans les biotechnologies), organise le 17 mars prochain, avec le soutien du laboratoire PIERRE FABRE et du cabinet de conseil CEPTON Strategies, un colloque qui présente les grandes réussites du secteur et ses perspectives. L’objectif est notamment d’inviter les jeunes générations d’ingénieurs à saisir les opportunités de carrières et d’entrepreneuriat : ” de la start-up à la multinationale, les biotechnologies, industrie des ingénieurs du 21ème siècle, constituent un gisement d’emploi majeur pour les 50 ans à venir”, précise Marc-Olivier Bévierre, président de XMP-Biotech.

Santé : « l’innovation sera le moteur de la hausse des coûts » (Le Figaro)

INTERVIEW – Pour Marc-Olivier Bévierre, associé du cabinet de conseil Cepton, la prise en charge globale de la santé sera plus efficace. Mais il faudra aussi choisir entre le maintien en bonne santé d’une large part de la population et la survie d’une poignée de patients.

Lire l’article sur le site du figaro.fr

LE FIGARO. – La santé coûtera-t-elle plus cher au cours des prochaines décennies? Marc-Olivier BÉVIERRE. – Oui et non. Les dépenses ne baisseront pas. Mais la prise en charge globale de la santé sera plus efficace. L’accent sera mis sur la prévention, le parent pauvre de la santé aujourd’hui, alors qu’elle permet des économies considérables. Les systèmes d’alerte précoce vont se multiplier. Par exemple, on saura identifier les quelques centaines de milliers de Français qui doivent être vigilants sur tel ou tel aspect de leur mode de vie et on pourra s’adresser directement à eux plutôt qu’à l’ensemble de la population. Par ailleurs, le recours à latélémédecine – consultation de spécialistes, analyses d’images à distance, etc. -, qui commence à fonctionner, à faible coût, dans les pays émergents, finira par se développer en France. On verra aussi se répandre les bracelets et autres objets connectés qui collectent des données de santé et facilitent la prévention.

Enfin, l’un des grands enjeux sera d’améliorer l’observance des traitements et le suivi des ­patients dans le temps, pour ­éviter des rechutes aux conséquences souvent lourdes. Pourquoi la croissance des dépenses de santé sera-t-elle plus rapide que celle du PIB? L’innovation sera le principal moteur du développement du coût de la santé. On la trouvera dans les médicaments et, plus encore, dans les dispositifs médicaux, qui finiront d’ailleurs par fusionner, d’une certaine façon, avec la miniaturisation des instruments médicaux ou l’inclusion de minidispositifs dans les médicaments pour s’assurer de leur absorption par les patients. Mais je ne crois pas que le coût des traitements, qui peut dépasser aujourd’hui un million d’euros par an pour certains cas rares d’hémophilie, continuera d’augmenter indéfiniment. Les outils de diagnostic seront plus nombreux et plus précis, ce qui permettra de faire le tri dans les ­médicaments à administrer à un patient. Et à terme, on trouvera sans doute des solutions moins coûteuses.

C’est inévitable. Le budget de la santé n’est pas illimité et des choix difficiles vont s’imposer entre le maintien en bonne ­santé d’une large popu­lation et la survie d’une poignée de ­patients. Les modalités de remboursement des médicaments évolueront-elles? Depuis de nombreuses années, des accords lient les tarifs et la quantité de médicaments consommés. Aujourd’hui, le ­partage des risques se développe pour des traitements chers. Si un médicament ne soigne pas le ­patient comme prévu, le laboratoire le rembourse, ce qui peut lui coûter très cher. À l’avenir, en dehors des innovations majeures, aucun produit de santé ne sera remboursé si son intérêt éco­nomique n’est pas clairement démontré.

L’industrie pharma de demain : 7 pistes pour se réinventer

L’industrie pharmaceutique fait actuellement face à 3 grands défis :
• L’innovation s’essouffle dans les grands domaines thérapeutiques. A horizon 2019, aucune innovation n’est par exemple annoncée dans les traitements de l’hypertension ou de la maladie de Parkinson. Le traitement de la dyslipidémie ne connaitra que 5 % d’innovation 1. De la même manière pour la polyarthrite rhumatoïde, le taux d’innovation ne dépassera pas 5 %.
• L’innovation thérapeutique n’est plus générée par les grands laboratoires pharmaceutiques mais par les petites entreprises de biotechnologies. En effet, 70% des produits actuellement en phase III proviennent de ces petites entreprises.
• Une réglementation de plus en plus sévère rend extrêmement difficile la mise sur le marché de nouveaux traitements.
Face à ces défis, il devient vital pour l’industrie pharmaceutique de s’adapter et de repenser son modèle en profondeur.

CEPTON prévoit une explosion du marché de l’hépatite C (Pharmaceutiques)

CEPTON, cabinet de conseil en stratégie spécialisé dans le domaine de la santé, vient de réaliser une étude indépendante sur le marché de l’hépatite C. Celle-ci prévoit une très forte croissance du segment qui pourrait atteindre 20 milliards de dollars à l’horizon 2020, contre 3 milliards aujourd’hui. Explications avec Marc-Olivier Bévierre, associé du cabinet CEPTON.

Évolution du marché de l’hépatite C

De nouveaux traitements de l’hépatite C sont en train d’apparaître, qui permettent d’espérer une éradication de la maladie dans les 10 à 15 ans à venir. Pour la pharma, ce marché ressemble fort à un eldorado. Qui seront les leaders demain? Cepton a analysé le pipeline et les perspectives de développement de ce marché prometteur.

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Les perspectives de développement du diagnostic moléculaire

Colloque France Biotech, le 7 juin 2012. Le diagnostic moléculaire est la clé de la médecine personnalisée, et en ce sens, ses perspectives de développement sont importantes. Mais la situation réglementaire et l’accès au marché sont encore peu structurés, très variables selon les pays et de nombreux freins subsistent aujourd’hui. CEPTON a participé au colloque de France Biotech sur ce thème le 7 juin 2012.

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Voir aussi l’article paru dans “Pharmaceutiques”

Les perspectives de développement du diagnostic moléculaire

Colloque France Biotech, le 7 juin 2012. Le diagnostic moléculaire est la clé de la médecine personnalisée, et en ce sens, ses perspectives de développement sont importantes. Mais la situation réglementaire et l’accès au marché sont encore peu structurés, très variables selon les pays et de nombreux freins subsistent aujourd’hui. CEPTON a participé au colloque de France Biotech sur ce thème le 7 juin 2012.

Demander le document complet en utilisant notre formulaire de contact Voir aussi l’article paru dans “Pharmaceutiques”

L’art de réussir les alliances (Le Figaro)

Beaucoup de chefs d’entreprise continuent de miser sur les fusions. Ils n’hésitent pas à investir des sommes importantes pour s’emparer d’une entreprise prometteuse ou d’un concurrent.
Cette stratégie est d’autant plus étonnante que de nombreuses études démontrent que ces opérations entraînent souvent des désillusions. « 70 à 90% des opérations de fusion-acquisition n’atteignent pas les objectifs fixés initialement et plus de 50% d’entre elles se révèlent destructrices de valeur selon une étude publiée par la Harvard Business Review », constate Bertrand Kleinmann, senior partner de Cepton Stratégies spécialisé dans le conseil en stratégie et transactions.

Ces lois qui ont bouleversé l’industrie de la santé sous Sarkozy (L’Usine Nouvelle)

Le quinquennat qui s’achève aura été marqué par le vote de deux grandes lois sur la Santé : une première loi en 2009, dite HPST ou loi Bachelot, qui introduit une réforme structurelle du système de santé, et la loi sur les produits de santé ou loi Bertrand, plus politique, qui fut votée en 2011 suite au scandale du Mediator®. L’impact de ces deux lois pour les industries de santé est important et n’a pas fini de se faire sentir.

Les perspectives de l’industrie pharma à l’horizon 2020

Le monde de la santé a changé. Au-delà de la récente crise économique qui semblait l’avoir épargnée, l’industrie pharmaceutique doit faire face aujourd’hui à des défis plus structurels: un encadrement plus strict des dépenses de santé par les pouvoirs publics, une nécessité impérative de relancer l’innovation, et des patients plus nombreux et plus exigeants. Face à ces changements, les acteurs de l’environnement pharmaceutique évoluent.

Médecine personnalisée : la révolution est en marche

Du profilage des patients aux thérapies géniques, en passant par le diagnostic moléculaire et de nouvelles formes de vaccination, les possibilités ouvertes par la médecine personnalisée sont immenses. C’est aussi un enjeu considérable pour l’économie des systèmes de santé, et bien sûr pour les grandes firmes pharmaceutiques, qui ont dû repenser en profondeur leurs démarches de recherche et développement.

Le concept de médecine personnalisée a été développé il y a deux décennies par la société suisse Roche, l’un des leaders mondiaux de l’industrie pharmaceutique. Le concept initial était fondé sur une réalité très simple dans la pratique médicale: le même médicament peut provoquer des réactions différentes selon les patients, et pour un patient donné, certains médicaments fonctionnent et d’autres non.

Avec l’introduction dans les années 1990 de l’Herceptine, un traitement pour le cancer du sein, Roche a démontré qu’il était possible d’anticiper, grâce à un simple test sur les patients, ceux pour qui le traitement serait le plus bénéfique, et ceux pour qui il ne le serait probablement pas.

Il est désormais possible de personnaliser les traitements, c’est-à-dire de n’administrer un médicament qu’aux patients qui réagissent positivement. L’impact de cette nouvelle approche est énorme: une efficacité accrue, moins d’effets secondaires, et plus de temps ni de ressources perdus pour un traitement inopérant.

Lire l’article complet sur Paristechreview.com

Le déclin inéluctable des visiteurs médicaux (Le Figaro)

Les laboratoires reconvertissent leurs forces commerciales en visiteurs formés pour s’adresser au secteur hospitalier plutôt qu’aux généralistes. “L’hôpital est un lieu stratégique où se jouera à l’avenir la concurrence entre médicaments. 80% des nouveaux médicaments y seront prescrits”, explique Marc-Olivier Bévierre, associé de CEPTON. La visite collective, proposée par la loi Bertrand, sera difficile à mettre en oeuvre.

La pharmacie fait son aggiornamento (Valeurs Actuelles)

Les assises du médicament sont en train de modifier les règles qui régissent l’industrie pharmaceutique. CEPTON stratégies est un cabinet de conseil qui aide les entreprises à s’adapter au changement. Rencontre avec Jean Reboullet, son fondateur, ingénieur venu de la chimie.
Pourquoi l’industrie pharmaceutique, essentiellement constituée de majors, fait-elle appel à un petit cabinet comme le vôtre?

La télémédecine : un rôle clé dans l’essor des soins à domicile

Qu’entend-on par « Soins à domicile » ? Il existe principalement trois types de prise en charge d’un patient à domicile, qui diffèrent en fonction du profil du patient et de la gravité de la pathologie traitée.
L’hospitalisation à domicile (HAD) L’HAD est véritablement un prolongement de l’hôpital au domicile du patient. Elle concerne les pathologies graves, en sortie d’hôpital (soins de suite de chimiothérapie, convalescence post-opératoire, grossesses pathologiques, soins palliatifs,…) qui nécessitent la mobilisation de moyens et de compétences médicales lourds. Aujourd’hui environ 80 000 patients sont pris en charge en HAD.
Les Services de soins infirmiers à domicile (SSIAD), associatifs ou libéraux Les SSIAD, ou Soins à Domicile (SAD) simples, concernent des pathologies moins graves ; ils permettent en général de retarder ou d’éviter l’hospitalisation. Ils concernent soit des patients âgés et dépendants, soit des patients jeunes atteints de maladies chroniques ou de handicaps graves.
Dans les deux cas, l’hospitalisation de ces patients serait trop coûteuse au regard des bénéfices médicaux attendus. Les SAD sont encore très peu structurés et organisés, et concernaient déjà un nombre considérable de patients, estimé à 14 millions en 2007.
Les Etablissements d’Hébergement de Personnes Agées Dépendantes (EHPAD) Les EHPAD sont des établissements de long séjour pour personnes âgées dépendantes, pour lesquelles une prise en charge médicale est souvent nécessaire (soins infirmiers lourds, escarres, traitement de la douleur, démences).

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Pharma 2015: le nouveau modèle

Moins de nouveaux médicaments, conditions de remboursement plus dures, charte de la visite médicale, plans de gestion du risque, retraits de produits, déremboursements, déficit persistant de la Sécurité Sociale, renforcement du pouvoir des centrales d’achat hospitalières…
L’industrie pharmaceutique, on le sent bien, doit changer de modèle commercial. Quatre grandes mutations sont en cours.