Regulatory strategies for value maximisation of early clinical stage assets

Prepare for partnering – Optimizing value in early development

There are many important reasons why a company would choose not to develop and commercialise a product on their own. The cost of development increases exponentially, making the final stages impossible to finance for many companies. Building a commercial organisation covering vast territories can be an equally daunting task.

Companies we work with have a clear definition of what it is they want to do and often their strategy is limited to discovering and developing proofs of concepts of products in a certain region; the rest is simply not part of their focus. Whatever the reason, the goal for many companies we work with is often to develop the product to a stage where partnering or out-licensing becomes feasible.

This white paper written by Niamh Kinsella, Biologics Expert, Paul Chamberlain, Biopharmaceuticals Expert, Josi Holz, Clinical Strategy Expert and Eva Lilienberg, Service area lead Global Development, focus on how you can strengthen your partnering negotiation position, reduce the time to the clinic and to help you determine value-adding regulatory milestones by applying integrated regulatory strategies, ultimately optimising the value of your asset at the point of exit.

 

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By:

Niamh Kinsella
Paul Chamberlain
Josefin-Beate Holz
Eva Lilienberg

 

 

 

 

 

 

 

Paula Salmikangas presents on Regulatory and scientific challenges for global development

Dr Paula Salmikangas, Director for Biopharmaceuticals and ATMPS, NDA Advisory Board, has been invited to present at the World Advanced Therapies and Regenerative Medicine Congress, 16 – 18 May, Business Design Centre, London.

Dr Salmikangas will speak in the Plenary Round Table Discussion Session: Process Development & Manufacturing Focus, with the topic title: Regulatory and scientific challenges for global development.

At this event you will have the opportunity to Research, Develop, Collaborate & Commercialise.

  • Meet 600 industry leaders from the pharma, biotech and research industry
  • Take part in 20 free seminars focusing on human application for stem cells, bioelectronic medicine, investment for AI in Healthcare and more!
  • Discover and experience the latest and most innovative products and solutions in the market showcased by 50 industry leaders
  • Be inspired by industry thought leaders during live interviews conducted on the exhibition floor
  • Discover the companies of the future in our innovation zone

 

Click here to find out more about the event.


 

Professor Carole Longson to join NDA as Scientific Adviser

Carole Longson MBE, former Executive Director and Board member at the National Institute for Health and Care Excellence (NICE), has joined the NDA Advisory Board. Carole will act as an adviser within NDA on matters relating to drug approval, scientific advice and Health Technology Assessments, areas in which she has had great impact in her previous role.


Carole brings tremendous research, academic and pharmaceutical industry experience to the role, including seven years as a Research Lead at GlaxoSmithKline R&D.

She has extensive expertise of directing multidisciplinary life sciences research programmes, managing large scientific departments and collaborating on multinational research grants.

Carole was a past member of the Scientific Advisory Committee for Innovative Medicines Initiative (IMI), the leading pan-European public- private partnership which funds health research and innovation. She also holds non-Executive Director and advisory roles in other scientific organisations in the UK and abroad. These positions give her a unique and extensive perspective on the changing face of industry.

Carole has unparalleled insight into the fast evolving medicines pipeline having spent the past 18 years at NICE where she has pioneered and led the organisation’s technology appraisal programme. Carole is highly respected as a leader in HTA & Market Access, both in the UK and internationally and was formerly President of Health Technology Assessment International.

Throughout her career and role at NICE, Carole has gained valuable understanding of how the public and private sector must continue to collaborate to meet the shared aims of ensuring medical innovation benefits patients in the UK.

Johan Strömquist, CEO NDA Group, commented on the appointment:
“I am delighted to see Carole join us. Not only will she bring a wealth of knowledge and experience to NDA that fits intimately with our strategic direction, her reputation in the industry and among her former Agency peers, also stems from her positive and collaborative personality.”

Werner Van den Eynde, Vice President NDA Advisory Services, commented:
“This appointment is a major step in our continuing aim to broaden our reach and expand HTA and market aspects into our drug development service offerings. It is also a testament to NDAs reputation amongst regulators and HTA bodies – NDA remains the undisputed prime destination for the greatest contributors to our regulatory and assessment systems.”


NDA media contact: anna.perrin@ndareg.com

About NDA
NDA is an independent consulting group with offices in Stockholm, London, Zürich, Munich, Paris, Princeton, Boston and San Francisco. Its mission is to ensure that good medicines reach patients without unnecessary delay. It accomplishes this by providing the pharmaceutical industry with a comprehensive range of professional drug development services focusing on regulatory affairs, health technology assessment, pharmacovigilance and quality assurance. NDA’s team of more than 150 full time professionals is comprised of more than 25% ex-regulators from major EU Agencies, and a specialist Advisory Board consisting of Europe’s leading regulatory and HTA experts. The NDA Advisory Board provides scientific advice to pharmaceutical companies supporting them in gaining fast and constructive assessment of applications from regulatory agencies and HTA bodies. www.ndareg.com

 

 

Free Webinar – Rational EU risk management for oncology medicines: time for a rethink

It is timely to reflect on how we can best implement the revised GVP module (V) concerning risk management in the interests of patients throughout the life-cycle of a medicine.

Join us on Thursday, 24th May to hear NDAs Dr. Bill Richardson, Medical Advisor, discuss factors to consider include:

  • Taking into account the needs of the prescriber and other healthcare professionals
  • Applying the resources of the marketing authorisation holder (MAH) effectively to comply with regulatory expectation
  • Ensuring risk management plans reflect only measures that MAHs can reasonably control while retaining the MAH’s duty of care
  • Remembering risk management during clinical development is intrinsic to Good Clinical Practice
  • Providing precise instructions for minimising risk in the protocol and investigator brochure to form the basis of the EU risk management plan
  • Designing pivotal studies based on the anticipated target group once marketed
  • Defining recommended conditions for safe and effective use of a medicine to minimise risk

Thus, how can we now sensibly apply the revised GVP module for risk management?

Dr. Richardson is an experienced ex-EU regulator who understands the detail by which a typical RMP will be assessed and who will provide practical guidance to help you produce compliant RMPs effectively and efficiently.

Click here to book your place today.


 

Dr. Bill Richardson qualified in medicine in 1980, and subsequently trained as an anaesthetist. He has over 25 years of regulatory affairs and pharmaceutical medicine experience, from clinical development to post-marketing. He joined NDA Group in 2014 after having worked for 11 years as a medical assessor at the UK medicines’ regulator (MHRA). He is an expert in pharmacovigilance and risk management – risk:benefit evaluation, risk management planning and scientific advice in the context of the current EU pharmacovigilance legislation, including the role of the QPPV. He has considerable expertise in the following areas:

  • Clinical development and clinical safety of medicines delivered by inhalation, particularly medicines for asthma and chronic obstructive pulmonary disease.
  • Clinical assessment of drug safety aspects of marketing authorisation applications in a wide range of therapeutic areas particularly: immunosuppressants including TNF inhibitors; epoetins; biosimilar products; oncology products including thalidomide and analogues, protein kinase inhibitors, and vascular endothelial growth factor (VEGF) inhibitors; anaesthetic agents/ICU medicines.
  • Assessment of new drugs, biologics, generics and EU safety referrals and major changes to marketing authorisations.
  • Training in pharmacovigilance particularly risk: benefit evaluation

 

Is a global regulatory and market access strategy the way to go?

Dr. Thomas Lönngren, Strategic Advisor to NDA Group and former Executive Director of the European Medicines Agency (EMA), has been invited to present at the Chief Medical Officer Summit, Omni Parker House, Boston, MA on 7th May.


Thomas will present along with Jeffrey Sherman, CMO, EVP R&D, Horizon Pharmaceuticals, in the session ‘Taking a Strategy Approach to Global Regulatory and Market Access Challenges’, were they will discuss:

  • Is a global regulatory and market access strategy the way to go?
  • Why isn’t EMA approval the same as market access in Europe?
  • What is the difference between EMA and FDA in regulating and approving medicines?
  • When and how to generate evidence that will satisfy regulators and payers
  • What is the best strategy to interact with regulators and payers?
  • Early access schemes in EU and how to qualify
  • How will trends like Real World Evidence influence regulatory decision making?
  • Brexit and its consequences for the EU regulatory system and how will it affect pharmaceutical companies

As well as presenting at the event, NDA Group is ‘Associate Sponsor’ of the CMO Summits, demonstrating its commitment and support towards the CMO community.

Please come by booth #2 and meet us;

  • Dr. Thomas Lönngren, Strategic Advisor to NDA Group and former Executive Director of the EMA
  • Laurie Smaldone-Alsup, MD, COO/CSO
  • Barbara Clendenen, Director, Business Development

The CMO conference is an annual gathering for physicians and scientists in biotech to exchange best practices in the advancement of drug development and business management. Although the program is primarily designed for CMOs of emerging biotech companies, CMOs of large pharma and other R&D decision-makers will also benefit.

To find out more about the event click here.


 

 

Meet us at PEGS Boston


 

NDA Group will be attending PEGS Boston, that takes place in Seaport World Trade Center, Boston April 30 – May 4, 2018

NDA supported over 40% of the new medicinal products that were approved in the EU during 2013 -2017. In 2016 NDA acquired PharmApprove, the market leader in managing critical FDA interactions to help us achieve the same results in the US.

If you are planning to attend this year’s PEGS, we would really like to meet up with you. We will have a few of our experts available at the event at booth 437:

  • Dr Niamh Kinsella, Biologics Expert
  • Dr Jenny Sims, Non Clinical Expert
  • Dr Josefin-Beate Holz, Clinical Strategy Expert

If you would like to arrange a meeting, please contact Niamh Kinsella, who will be happy to assist, niamh.kinsella@ndareg.com

 

Presentations

Three of our experts will present at the event:

Jenny Sims:

Monday 30th April 12.20 pm, Immunogenicity Case Studies and Clinical Management Track.
Title: Early Development Strategy for Bacterial- or Viral-Vectored Gene Therapies: 2 Case Studies

 

 

Josefin-Beate Holz
Monday 30th April and Tuesday 1st May, Poster Session A
Developing an Integrated Summary of Immunogenicity (ISI) to Effectively Manage Regulatory Risks in Product Development

 

 

 

Niamh Kinsella
Wednesday 2nd May and Thursday 3rd May, Poster Session B
Maximising Value in Early Development

 

 

 

 

Click here to find out more about the event.

We look forward to hearing back from you about a meeting and to seeing you at the event!

 

 

 

Europe vs USA: new drug product approvals in 2017

By Terese Johansson PhD, Consultant, NDA Group

It’s been an exciting year for new drug approvals! Many of the new drugs approved during the year address significant and meaningful needs or give additional therapeutic choices for patients and physicians. In the US we have seen a ground breaking approval in oncology that changes the way we look at and relate to indications; in addition the first digital pill has seen the light of day.

The following summary provides an overview of the key findings and an analysis of what the data means for the industry. The data is visually represented in an infographic below.

 

More approvals and more novel drugs

Last year there were a total of 103 new drug approvals granted in US and EU together that meet our selection criteria (i). Of these new products, 15 were approved only in the EU, 52 only in the US, and 36 were granted approval in both regions. It’s a large improvement compared to last year’s figures that showed 19 only in EU, 19 only in US and 36 in both regions, with a total 74 new approvals. In addition, 56 of the new approvals in 2017 were classified as novel drugs (ii). Our data show that the trend to apply for approval in the US prior to registration in the EU is, as usual, still a regular practice.

In the US expedited drug development and nonstandard review approval pathways are the new normal. In 2017 special approval and designation procedures like Fast Track, Breakthrough (BTD), Accelerated Approval and Priority Review was used for 37 of the new approvals, in many cases more than one of these approval pathway designations was granted per product. FDA has a higher rate of granting special approval status compared to EMA, 37 vs 10. One can only conclude that the policy groundwork laid by FDA in the past years to speed up drug approvals with the introduction of shorter nonstandard approval pathways has a clear overall effect on shortening the mean approval timelines.

Ground Breaking Oncology approval and the rise of CAR-T therapies

It’s been an exciting year for oncology with a total of 27 new approvals, so far 12 of these are only approved in the US and one of them were rejected by the EMA in 2008 (Mylotarg, gemtuzumab ozogamicin), however EMA now granted approval during 2018. A ground breaking approval was granted in the US where FDA (CDER) approved Keytruda (pembrolizumab) by Merck & Co Inc as the first drug ever where a biomarker (PD-1 (programmed death receptor-1) defines the indication (iii). The scientific rationale underpinning the Keytruda approval has effectively created a single therapeutic approach for patients with different tumour types, allowing extrapolation of the observed treatment effect to diverse tumours. The approval is likely to have implications for how the drug development process is pursued in the future, in oncology, but most likely also for other therapeutic areas as science progress.

Furthermore, also in oncology, the two first chimeric antigen receptor T-cell (CAR-T) therapies have been approved by FDAs CBER unit, its Novartis Kymriah (tisagenlecleucel, for the treatment of B-cell acute lymphoblastic leukemia) and Gilead’s Yescarta (axicabtagene ciloleucel, for the treatment of relapsed or refractory large B-cell lymphoma). Both drugs are currently under assessment in EU with Kymriah being granted an accelerated assessment by CHMP.

The Approval of a Pill with a Digital Sensor

Other noteworthy approvals from the US includes Abilify MyCite, the first pill with a sensor that digitally tracks if patients have ingested their medication (aripiprazole, for the treatment of schizophrenia, acute treatment of manic and mixed episodes associated with bipolar disorder and as an add-on treatment for depression) (iv).

Noteworthy Orphan Approvals

Several important ultra-orphan medicines have been approved in the US and EU, Mepsevii (vestronidase alfa-vjbk, for the treatment of the inherited metabolic condition mucopolysaccharidosis type VII, also known as Sly syndrome, approved in the US only) and Brineuria (cerliponase alfa, an enzyme replacement therapy for the treatment of Batten’s Disease, approved in both regions). With more treatments for orphan diseases hitting the market the debate on the pricing of these drugs intensifies: Drug developers are increasingly meeting the treatment demand from the patients and physicians but are the payers willing to pay the price? Drug developers will benefit from being prepared early on to develop strategies to ensure patient access to and affordability of their orphan agents.

The Birth of EU Public Hearings

2017 is also the birth year of public hearings at EMA. The EU Pharmacovigilance legislation enabled the Pharmacovigilance Risk Assessment Committee (PRAC) to hold public hearings during certain safety reviews of medicines allowing the committee and EMA to engage with citizens in the EU. Unlike the US, where public hearings for new drugs approvals has been going on for years, the system in EU focuses on post approval hearings in the context of urgent safety procedures / referrals and public hearings for new drug approvals is out of scope for now.

In the US public hearings of new drug approvals and how to deal with them can be an important part of drug developers planning for success. Drug developers aiming for US approval should consider building awareness of public hearings into their planning and ongoing relations with medical societies, patient organisations, physicians and other healthcare professionals. The perspectives from these groups can provide an important context for the safety and efficacy data submitted by drug developers and have additions to the severity and impact of a condition and the limitations of current standards of care. The Sarepta Exondys 51 approval in 2016 (for the treatment of Duchenne muscular dystrophy, only approved in the US, a review decision from EMA is expected during 2018) is an excellent example of a public hearing playing an important role in the approval process of a new drug. The approval showed the US Advisory Committees receptiveness to public perspectives as they evaluate the benefit-risk of new drug under review.

The Era of New Designation Pathways Continues

It’s also been an exciting year for drug developers in advanced medicines (e.g. ATMP in EU and Regenerative Medicines in US). FDA has during 2017 launched its new designation pathway Regenerative Medicine Advanced Therapy (RMAT) to further enable the development of these drugs. RMAT may be considered as analogous to BTD for regenerative medicines, with some additional advantages in comparison: it does not require evidence to indicate that the drug may offer a substantial improvement over available therapies. The RMAT designation gives drug developers access to increased meeting opportunities in a manner comparable to BTD therapies.

In EU, special designation pathways and approval procedures is not as common as in the US. In March 2016, EMA launched PRIME (PRIority MEdicines), the EU counterpart to FDAs BTD. Last year the NDA Group published data showing that most products approved for PRIME was from companies based in US and most of the companies also already had BTD (v).

It is too early to tell if RMAT and PRIME will add to the strategies used by some companies that see cumulative advantages and/or benefits from obtaining multiple designation pathways, a phenomenon used mainly in the US and known as ‘layering,’ or ‘stacking’ of special designations with the intent to increase overall product value.

Continued Negative Trend of First-in-class Medicine Approvals

The approvals for targeted novel, first-in-class mechanism of action drugs continue to decrease, a trend that has been going on for years. Is it a sign of drug developer’s increasingly competitive nature around targets that “work” in specific diseases? If this is the case, drug developers can expect the competition on pricing amongst innovator products to increase and become the norm from the beginning. Historically, price competition has been occurring later on during the life cycle. In an environment where it becomes increasingly important to distinguish oneself, drug developers should focus on creative clinical strategies for differentiation. This could include co-development of biomarkers and tests to target sub-populations, companion diagnostics and innovative designs for dosing and patient follow-up.

Small and Medium Sized Pharma Dominate

For the first time since we started mapping the new drug approvals small and medium sized pharma have surpassed big pharma (vi) – quite an achievement! In total small and medium sized pharma contributed with 51% of the new drug approvals, to be compared to 49% from big pharma.

NDA supported over 40% of the approvals in the EU

NDA had a strong presence in the EU regulatory arena and supported over 40% of the new products approved from 2013 to 2017.
To read the statistics of new drug product approvals from last year click here.


Data collection and disclaimer

(i) The data was gathered from the EMA and FDA official websites, as reported on the FDA and the EMA official websites on January 2018, The data collected contains drug approvals for new active substances (chemical, biological, biotechnology or radiopharmaceutical substance), new molecular entity, new biological entity, new drug combination, biosimilars, new active ingredient and vaccines, excluding only generic and duplicate applications from the data. As it is challenging to pull together data from two regions with different classification and reporting styles some general inclusion and exclusion criteria to create consistent indicators of the yearly trends in the EU vs the US has been applied. The above article provides an overview of the key findings and an analysis of what the data means for the industry. The data is also visually represented in an infographic. As experience tells us, the final number of approvals reported normally fluctuates for some time after the end of the year, as the Agencies go through their house keeping processes. There could therefore be some slight changes to the findings outlined in this report before the data is completely finalised. The PRIME analysis was based on publically available data from the EMA website and by mapping publically disclosed BTD.

(ii) FDA Novel Drug Approvals for 2017
https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm537040.htm
https://www.fda.gov/BiologicsBloodVaccines/DevelopmentApprovalProcess/BiologicalApprovalsbyYear/ucm547553.htm

(iii) First FDA Approval Agnostic of Cancer Site – When a Biomarker Defines the Indication. Lemery S, Keegan P, Pazdur R. N Engl J Med. 2017 Oct 12; 377(15):1409-1412

(iv) FDA approves pill with sensor that digitally tracks if patients have ingested their medication
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm584933.htm

(v) PRIME time for early designation pathways in Europe, T Johansson, Pharmafocus June edition 2017

(vi) The list of the top 50 pharma companies in 2017 was obtained from: EvaluatePharma 2017 Evaluate Ltd www.evaluate.com