FDA Breakthrough Designation Approval: Challenges & Tips from Roche’s Dr. Niklas Engler

Since being signed into law on 9th July 2012, the FDA’s Breakthrough Designation has changed the face of drug development. In November 2013 Roche’s monoclonal antibody, Gazyva, became the first medicine designated as a Breakthrough Therapy and in the next two years a further 37 approvals were granted. This increasing trend has continued into 2016, with a raft of new drugs given approval in the first two months of the new year.

Roche continue to be at the forefront of the industry and have had a hand in more than one of these new approvals. In January their drug venetoclax (ABT-199), developed in partnership with AbbVie, received a third Breakthrough Therapy Designation for use in combination with hypomethylating agents, to treat patients with first-line acute myeloid leukemia (AML) who cannot receive high-dose chemotherapy. Then just this week it was announced that ocrelizumab (OCREVUS) has been given BTD approval for treatment of patients with primary progressive multiple sclerosis (PPMS).

Early last year we spoke to Dr. Niklas Engler, Head of European Technical Development for Biologics at Roche, about the company’s success with the FDA’s Breakthrough Designation and the challenges it creates.


“The FDA’s Breakthrough Designation has created a direct dialogue between sponsors and the agency. For Gazyva, which attacks targeted cells both directly and together with the body’s immune system, we had weekly exchanges; the speed in which the FDA was working with us was really impressive.”

Technical Support Teams

“The big challenges we face at the moment aren’t necessarily protein production, that is fairly well understood, it’s how technical teams support variations in clinical trials, whether it’s an accelerated programme such as FDA Breakthrough Designation, or heavily gated programmes where you don’t do any technical support for a long time and then have to catch up very quickly.”

Cost and Resources

“Obviously, the financial and personnel investments are huge for such as product so you have to make sure you have the right product in place and all the departments are aligned – technical, clinical and non-clinical development. Because once you jump on that train you accelerate very quickly. If you are not prepared you can really slow down any accelerated advantage you once had.”

Supplying the market

“If you want to go for a large indication like the PD-1 and PDL-1 markets, you need to make sure everything is in place to supply. This is a big topic for the FDA, they don’t want difficulties in supply.”

Want to find out more about this topic? Gargi Maheshwari (Executive Director, Biologics Process Development and Commercialisation, MSD) will be talking on Merck product Keytruda’s FDA Breakthrough Designation at BioProcess International European Summit in Vienna. Her session – “Keytruda – Acceleration of a Breakthrough Therapy…What to do when CMC is on the Critical Path” – is at 9.25am 11th April. Find out more and see the full agenda here.

3D tissue printing breakthrough sends excitement through regenerative medicine industry

On a day that has seen the UK’s newspapers run front page stories on the benefits and successes of science’s golden child – the CAR-T cell, other news has surfaced of another equally successful breakthrough in the field of regenerative medicine.

First published in Nature Biotechnology, a team at Wake Forest Baptist Medical Centre has developed a new technique that 3D-prints living body parts, which when implanted into animals function normally.

Although similar techniques where biodegradable scaffolding is built and then ‘soaked’ in cells are already in use for human patients, the science of tissue regeneration in the past has been limited by the enormous challenge of keeping the cells alive. Generally speaking once the tissues become thicker than 0.2 millimetres the cells become starved of nutrients and oxygen.

To combat this limitation the team, led by Professor Anthony Atala, has developed a ground breaking new technique that creates tissues laden with micro-channels more akin to a sponge, which allows the nutrients to be delivered and penetrate the tissue.

In a joint publication with Hyun-Wook Kang, Sang Jin Lee, In Kap Ko, Carlos Kengla and James J Yoo, Professor Atala writes that the challenge of producing “3D, vascularised cellular constructs of clinically relevant size, shape and structural integrity” can be overcome by their “integrated tissue-organ printer (ITOP)”.

ITOP can create stable tissue constructs of any shape at a human-scale. Explaining how the technology works, the paper details:

“Mechanical stability is achieved by printing cell-laden hydrogels together with biodegradable polymers in integrated patterns and anchored on sacrificial hydrogels. The correct shape of the tissue construct is achieved by representing clinical imaging data as a computer model of the anatomical defect and translating the model into a program that controls the motions of the printer nozzles, which dispense cells to discrete locations.”

The real genius though is the addition of microchannels into the tissue that facilitates the diffusion of nutrients to printed cells (the sponge like quality) thus overcoming the 0.2 mm thickness limit of tissue constructs.

The technology has been demonstrated in mandible and calvarial bone, cartilage and skeletal muscle, with the future aims to produce tissues for human complex tissues and solid organs.

Speaking to the BBC, Professor Atala explains how this works in the real world,

“Let’s say a patient presented with an injury to their jaw bone and there’s a segment missing. We’d bring the patient in, do the imaging and then we would take the imaging data and transfer it through our software to drive the printer to create a piece of jawbone that would fit precisely in the patient.”

Although this breakthrough has got many in the field excited, Professor Atala has cautioned that additional research is needed before ITOP tissue constructs can be used in patients, but mused that “it will be less than a decade before surgeons like me are trialling customised printed organs and tissues. I can’t wait!”

Image Credit: Nature BioTechnology

Francis Crick Institute Scientists Granted License to Edit Genes in Human Embryos – What will the Initial Impacts be?

In a global first, the UK’s Human Fertility and Embryology Authority (HFEA) have granted permission to a group of London-based scientist to edit the genomes of human embryos for research. Announced on 1st February 2016, the endorsement is the first of its kind by any national regulatory authority.

The approved research application from the Francis Crick Institute led by Dr Kathy Niakan is aimed at identifying and understanding the gene human embryos need to develop successfully. The research team will look at the first seven days of a fertilised egg’s development in the hope of providing important knowledge for understanding how a healthy human embryo develops.

Dr Niakan will be using CRISPR-Cas9 technology which enables the scientists to modify, identify, or replace genetic defects.

Commenting on the news, Paul Nurse, Director of the Crick, explained: “I am delighted that the HFEA has approved Dr Niakan’s application. Dr Niakan’s proposed research is important for understanding how a healthy human embryo develops and will enhance our understanding of IVF success rates, by looking at the very earliest stage of human development.”

So what will be the initial impact of this authorisation?


With a topic such as genetically modified human genomes, controversy will not be far behind, with those opposed to the authorisation believing that this will open the door to ‘GM babies’.  It must though be made clear that this authorisation specifically states that it will be illegal for the scientists to implant the modified embryos into women.

Speaking on the ethical implications of the decision, Dr Sarah Chan from the University of Edinburgh said:

“The use of genome editing technologies in embryo research touches on some sensitive issues, therefore it is appropriate that this research and its ethical implications have been carefully considered by the HFEA before being given approval to proceed.”

“We should feel confident that our regulatory system in this area is functioning well to keep science aligned with social interests.”


Moving away from the controversy, it is good news for those receiving IVF treatment. With the increased knowledge that will be gained from the research, IVF success rates should dramatically improve thanks to the focus on miscarriage and fertility. Speaking to the BBC, Dr Kathy Niakan has said that the reason why she applied for the approval to edit human embryos was that “we would really like to understand the gene needed for a human embryo to develop successfully into a healthy baby”.

Dr Niakan went further to explain that “the reason why it is so important is because miscarriages and infertility are extremely common, but they’re not very well understood”.

Ethical Approval

The research is still in need of ethical approval before the programme can begin, but it is looking likely that this will be granted and the research will begin in the next few months.

With the research likely to add to the basic scientific knowledge needed for assisting infertile couples becoming parents, and to reduce the heartbreak of miscarriage, this is but one practical positive that will hopefully come from the work of Dr Niakan and her team.

Not only does the research have the potential to greatly assist in IVF treatment, it is another display of the excellent position the UK holds in the genome editing field of research and the advances being made by UK scientists.

At Cell Therapy Manufacturing & Gene Therapy Congress on 2nd – 5th February in Brussels, industry leaders will discuss technical and commercial strategies to deliver gene therapy products to patients. See the full agenda and book tickets at https://celltherapy.knnlab.com/.

The Prime Medical Group: The Value of Medical Communications for Gene Therapy

With Cell Therapy Manufacturing & Gene Therapy Congress less than a week away, we spoke to one of the exhibitors presenting in Brussels:

“The Prime Medical Group is delighted to be presenting at next week’s Cell Therapy Manufacturing and Gene Therapy Congress. The congress will provide a forum for delegates to discuss technical and commercial strategies for cell and gene therapies.

The Prime Medical Group has worked extensively in this area, providing strategic communications support for several orphan drugs and rare diseases, as well as developing and implementing the communications programme for the only gene therapy approved in Europe.  Howard Sinclair (Strategic Director – Rare Diseases and Gene Therapy) and Andrew Jobson, PhD (Scientific Director – Rare Diseases and Gene Therapy) will present on Tuesday 3 February at 12:10pm. The presentation will focus on the importance of an effective medical communications strategy and plan, as well as the key considerations when bringing an orphan drug or gene therapy to the market to ensure optimal return on clinical studies investment.

‘This is an exciting opportunity for The Prime Medical Group to share our experience and expertise with some of the leading figures in the industry,’ Howard commented. ‘We have successfully partnered with pharmaceutical and biotech companies over the years and understand the challenges faced when developing an impactful communications programme for orphan drugs and rare diseases as well as gene therapies.’

In addition to presenting, The Prime Medical Group will also have an exhibition booth at the congress allowing delegates to discuss their specific communication needs with the team in more detail.”

Cell Therapy Manufacturing & Gene Therapy Congress is being held in Brussels on 2nd – 5th February 2016. See the full agenda and book tickets at https://celltherapy.knnlab.com/.  

The Prime Medical Group: Established in 1997 The Prime Medical Group is a leading medical education and communications agency, committed to creating outstanding medical education and communication programmes with global, regional or national implementation. To learn more their therapeutic experience or services visit www.prime-medica.com.

Cell Therapy: Three Predictions for the Future of the Industry

There is a palpable air of excitement and enthusiasm around the cell therapy industry and a sense that, as Christopher Bravery of Consulting on Advanced Biologicals, puts it: “cell therapy has taken off”.

There have been tremendous breakthroughs as the field has matured over the last 10 years, but we want to know what’s next: what exciting developments can we expect going forward, over the next 5 to 10 years? We put this to our panel of experts and these were their top 3 breakthrough areas:

1) Cures, not just treatments.

To date, most biopharmaceuticals offer treatment, not a cure. All that could be about to change: Jason Carstens, of the Fred Hutchinson Cancer Research Center, is excited about the advancements made in the CAR T-cells field. He says it’s mind-boggling that we are actually talking about a cure for cancer. He continues, “if I had a crystal ball and was looking forward to some potential breakthroughs, I would say it’s in the area of regenerative medicine where we have the ability to repair spinal cord injury for example, cartilage injury, bone damage, cardiac damage and really have a great impact on the quality of life for people.”

2) Cell kits: the microchip of the healthcare industry

John Rowley, of RoosterBio, says the future of our biotechnology healthcare products are going to incorporate stem cell technologies. For this to happen, stem cells need to be provided, very similarly to microchips, in formats that enable product development. He explains, “technology revolutions happen when kits come on the market. They allow anybody to gain access to a technology – making it easy to use, simple, affordable, and robust. Something that works every time.” Looking to the future he sees, “a day of a true stem cell reagent where you’re able to take out 50 million, 100 million cells from the freezer, thaw it out and use it directly in an experiment. And where that’s really going to be huge is the tissue engineering world.”

3) Improvements in Manufacturing Technology

Aby Mathew of BioLife Solutions, believes that over the next 5 to 10 years we will see developments on both the clinical and manufacturing sides. On the clinical side he expects that more therapies will get approval and we’ll know they’re working at the patient level.

On the commercial side, he sees that “manufacturers of these therapies will be able to optimize their processes a little bit better and also be able to drive the cost down, in combination with relationships with suppliers, who can now generate these tools and supplies on a larger scale.”

He hopes that the lower costs will mean that these therapies can reach a much wider patient population, whether you are in a first world or third world country.

Over 50 speakers and 200+ industry pioneers will be discussing the future of cell therapy at the Cell Therapy Manufacturing & Gene Therapy Congress in Brussels on 2nd – 5th February 2016. Join the conversation at https://celltherapy.knnlab.com.

Bringing Orphan Drugs and Gene Therapies to Market: Maximising ROI through an Effective Communications Plan

Businessman with business plan concept analysis strategy questions

Howard Sinclair, Strategic Director – Rare Diseases and Gene Therapy, The Prime Medical Group, UK, and Andrew Jobson, PhD, Senior Editorial Manager – Rare Diseases and Gene Therapy, The Prime Medical Group, UK, are talking at Cell Therapy Manufacturing & Gene Therapy Congress on Wednesday 3rd February in Brussels. Here they explain what they’ll be talking on:

“There are a multitude of urgent and critical areas to address in further developing your orphan drug or gene therapy to achieve the next milestone. They consume all your team’s energy, resources and time, and there never seem to be enough hours in the day. Against this reality, is creating a communications plan really that important? – Yes! Won’t the external communications just happen naturally anyway, as the relevant data become available? From decades of experience supporting everything from mega-blockbuster first-in-class agents, to very specialised medicines for the most obscure ultra-rare diseases, we would respectfully and emphatically answer: No.

Unique challenges exist for rare diseases, orphan drugs and gene therapies that require tailored solutions, distinct from standard approaches. Creating a robust, evidence-based, authentic and compelling scientific narrative is the starting point – and you will need a sound plan to effectively share this with potential product users, key influencers and the broader healthcare community. This could include clinical trial investigators, practicing specialty clinicians, primary care providers, nurses and payers.

An effective strategic communications plan is critically important, enabling you to optimally engage with your target audiences at the right time (which will likely vary over the course of the development of your asset) to achieve your immediate and long-term goals, whether it’s accelerating clinical trial accrual or ensuring optimal awareness and adoption into clinical practice upon market authorisation. Early development and initiation of a tailored, proactive and cohesive communications plan is arguably even more critical for orphan drugs and gene therapies to ensure your limited resources are most effectively channelled.

Topics to be covered will include:

  • Adding value to your product/clinical studies programme with a tailored medical communications plan.
  • Addressing the specific challenges for a medical communications plan in orphan drugs, rare diseases and gene therapy.
  • Driving the communications strategy through a focus on the unmet needs of both the patient and the healthcare professionals.
  • Defining the key elements of an optimal communications plan.
  • Making the plan happen – driving the initiation, management and delivery.

Creating a robust and tailored strategic communications plan is critical to success – we will explore the why, what and how.”

See the full agenda for Cell Therapy Manufacturing & Gene Therapy Congress and buy tickets at https://celltherapy.knnlab.com.