Anonymous Jan 08

Interview: market authorisation, HTA involvement in early drug development and working with your HTA

Dr Leeza Osipenko, NICE

Dr Leeza Osipenko is Associate Director of NICE and works closely with EMA, MHRA, European HTA agencies and EUNETHTA. She chairs most of the national, international and parallel scientific advice meetings, signs off all key deliverables produced by the team and leads on business development activities via frequent public speaking engagements

Phacilitate: The cell & gene therapy field has taken some major steps forward in terms of licensed products over the past few years; how do NICE and its staff stay abreast of swiftly emerging novel technology areas such as this one?

Dr Osipenko: One constant throughout NICE’s 16 years of existence is that our methods of evaluating technologies have had to continually change to keep pace with new developments. Cell and gene therapies are no exception. Regenerative medicine poses some unique challenges – but we are aware of them and feel confident we can rise to them.

NICE has already appraised two regenerative medicine products which helped us to gain valuable insight into the issues associated with these therapies. We also spend a lot of time speaking to companies in this field, to keep up to date with developments.

The UK Regenerative Medicine Expert Group’s report in March 2015 prompted further consideration of regenerative medicines. In response to a recommendation, we began a project to further explore the application of our appraisal methodology to regenerative medicines and cell therapies. This study considers a hypothetical new product based on CD19 CAR T cell therapy. As part of the exercise we will be analysing multiple scenarios, varying parameters such as estimates of effectiveness, maturity of evidence, discounting rates, price and payment models and managed access arrangements. What the study will do is help us identify areas where we may need to adapt our methods or processes. It will also inform the development of a framework for the developers of regenerative medicines to help their understanding of how NICE evaluates clinical- and cost-effectiveness.

Our outreach activities to developers is also important. In September in London we are running our first ever NICE Scientific Advice educational seminar designed specifically for the developers of regenerative medicine products. Our aim is to reach out to the industry and academics to communicate the need for evidence generation from the payer’s perspective.

We collaborate very closely with the Cell Therapy Catapult in the UK, EMA, MHRA, DH and NHS England to understand and address the challenges posed by regenerative medicines products.

Phacilitate: Many of the first cell and gene therapies to achieve market authorisation are/will be for rare or even ultra-rare indications, how does this impact your work in assessing them?

Dr Osipenko: NICE already has considerable experience of appraising products for rare diseases and will continue to build on this. For example, our Highly Specialised Technologies programme evaluates products for very rare diseases, and we have had to develop new methods and processes for doing this. More broadly, many orphan products have been, and continue to be appraised by our Technology Appraisal programme.  

Phacilitate: Sparked by Glybera, there is much debate currently around the value one can attach to a potentially curative, one-time therapeutic for a severe disease, what are your thoughts on what is feasible in this regard?

Dr Osipenko: The evaluation framework used in NICE Technology Appraisals can and does apply to potentially curative treatments. Regenerative medicine presents some perhaps unique challenges: their mode of action and method of application is quite different. They may provide a cure rather than simply alleviate symptoms but, as a result, come with very high up-front costs. Other challenges include assessing claims of long-term /lifetime benefits, changes in costs due to scaling up of production, potential longer-term patient safety issues due to persistence.

We are working hard to investigate and understand whether the conceptual differences between regenerative medicine and other types of technologies (e.g. pharmaceuticals and medical devices) require a different approach to the conduct and assessment of cost-effectiveness. Risk-sharing schemes may have an important role in ensuring patient access to products as soon as possible.

Phacilitate: HTAs are getting more and more actively involved in the earlier stages of drug development, e.g. through involvement in the adaptive pathway pilot. Can you outline the HTAs role in that particular example and perhaps discuss NICE's goals in this particular regard?

Dr Osipenko: We have been involved closely in the recent adaptive pathway pilots, and have participated in most discussions with companies going through this scheme. Some of these technologies were regenerative medicines products, and safe harbour dialogues were a very productive learning curve for everyone – the industry, regulators and HTA agencies.

The safe harbour format allows companies to put forward proposals that will interact in a different way with existing processes and the iterative dialogue allows us to explore the implications. For example, companies are proposing further UK evidence generation to support subsequent regulatory and HTA activities. Some of the methodological work at NICE has resulted from learning derived through these early dialogues with industry.

The benefits of these kinds of schemes are clear: an early sign from regulators about the potential of a new technology; better interaction with bodies such as NICE and commissioners who are part of these projects; and the additional data and experience of using these medicines in the clinic. All result in a smoother path to market once the licence is gained.

We also think that at the other end of the pipeline, it’s really important that those responsible for commissioning these new technologies are clear about the potential benefits of a new technology. So for example we are working with NHS England on how we use ‘real-world’ clinical evidence, rather than only clinical trial data, on a scheme called Commissioning through Evaluation, a new approach to evaluating promising specialised treatments for which there is insufficient evidence to support routine commissioning.

Phacilitate: Any general advice for the developers of the next wave of cell & gene therapies in terms of how to work with NICE and other HTAs?

Dr Osipenko: Definitely! Whether the product ends up undergoing an evaluation with us or by any other part of the healthcare system, the requirements from the payer for evidence generation are similar:

  1. Developers should be able to demonstrate the value of their product
  2. Early dialogue with payers during product development in my view are essential to understand and be able to address evidence requirements in the product development phase
  3. Come to us for Scientific Advice prior to finalising trial plans and discuss with us your clinical plans as well as economic modelling.

We collaborate closely with EMA and MHRA, and run parallel and joint advice projects. To meet the needs of SMEs, we have developed a faster and cheaper offer and we are happy to have an informal discussion with any company potentially considering HTA Scientific Advice.