Is Gene Therapy still on the brink of Commercial Success?

It is evident that there is still an imbalance between commercial viability from manufacturers and price considerations of payers.

launch markets

Let’s take this recent-ish example of misalignment in the case of BlueBird Bio and Zynteglo, the one-time gene therapy treatment for beta-thalassemia.

Here Bluebird Bio set their price at $1.8 million but were unable to come to an agreement on its price with the G-BA. This led to BlueBird Bio withdrawing Zynteglo from the whole European market citing challenges to achieving appropriate value recognition and market access.

It’s likely that this decision is related to the global pricing implications if a lower price were negotiated in Germany. As a Germany is a heavily referenced market in terms of international reference pricing (IRP), its likely this was a strategic decision for commercial viability.

What is GPI’s insight on the current state of cell and gene therapies (CGT)?

  • Our analysis on cell and gene therapies revealed that the average price payers accepted for orphan CGTs was way higher than for oncology or non-oncology CGTs.
  • The average price was over €1M across France, Germany, Italy, and UK for orphan CGTs, but only up to an average of around €300K for non-orphan.
  • The reason why payers were able to accept higher prices were because of high research and development (R&D) costs, little or no competition available, small population and high unmet need.
  • In addition, some markets have the infrastructure to incorporate innovation in their HTA (health technology assessment) process, which benefits CGTs – like France, Italy, UK. But for Germany, do not consider innovation as much as it does clinical evidence.

Given these challenges, particularly as the landscape moves towards more personalised, one-time treatment options and CGTs, payers have tailored their approaches to HTA.

First Launch Markets in Europe for Orphan Assets

Here we outline some examples from the first launch markets in Europe, namely, France, UK and Germany.

Listen to audio: Kate Anstee (Associate Director, Consulting | GPI) outline these examples from first launch markets in Europe.


In France, manufacturers can apply for an early access authorisation. This was previously the ATU but has been expanded to cover non-orphan products. As a general rule, products with an orphan designation are likely to meet the criteria for early access because:

  • There is no appropriate treatment.
  • Cannot delay initiation of treatment.
  • Presumed efficacy and safety based on the results of clinical trials.
  • Presumed to be innovative, notably compared with a clinically relevant comparator.

This early access allows free pricing as with the ATU but has been adapted to meet the payers cost-containment with a payback scheme based on actual revenues rather than forecast. It also works for the manufacturer, allowing data collection as part of the scheme that can then be used to support the HTA submission. More market-specific evidence can be favourable when the clinical trial data is highly uncertain.

Therefore, for the launch strategies of new assets, the early access authorisation would make France a great first launch market.


In the UK, we have two processes.

  1. Highly Specialised Technology Appraisal

This is an established process for orphan drugs that treat ultra-rare conditions. NICE acknowledge that these ultra-rare conditions have a small patient number and often a high cost so includes a higher ICER threshold of £100,000. Even if the orphan product exceeds this threshold NICE apply an additional QALY modifier to determine if the product would be considered cost-effective. Regardless of this process, most orphan drugs have a simple discount of managed access agreement in place to reduce costs.

2. Standard Technology Appraisal

For other orphan drugs that treat rare conditions, this process is followed. This has potential disadvantages for high-cost drugs that exceed the £30,000 ICER threshold. However, the new adoption of the disease severity modifier could allow additional QALY weight to be applied for severe diseases. This would align the two-appraisal process for all orphan drugs. How this is applied across orphan products is still within its infancy but is certainly one to watch as an opportunity for new orphan products.


Germany has been a first launch market for many years.

The free-pricing period and automatic reimbursement at day of launch for orphan drugs is a great incentive for manufacturers.

The assumption of additional benefit for orphan drugs allows the G-BA to make reimbursement and price decisions on the likelihood and extent of benefit based on the uncertain clinical evidence. The difference with this process is that once the annual sales have exceeded a threshold a full benefit assessment is triggered which requires further evidence. For many years this threshold has been €50 million but as of 2023 this threshold is reducing to €20 million.

As these high-cost orphan products continue to launch, this could present a challenge where data remains highly uncertain. Therefore, for the launch strategies of new assets, Germany may no longer be an optimal market for first launch. 

How is innovation considered in France, UK, and Germany regarding processes and policies of orphan drugs?

These markets consider innovation in various amounts. For instance:

  • Germany focuses only on clinical benefit and innovation is not considered.
  • France looks at it in terms of effect of therapy e.g., curative, unmet need and specifically if there’s any additional value in formulation. It’s also considered in the EAA (Early Access Authorisation).
  • England look at innovation as a specific part of the HST (Highly Specialised Technology Appraisal). It’s sometimes covered in the TAs and may become more common with the new reform.

Are you looking for market insight to secure your assets success?

It’s no secret that there is still an imbalance between commercial viability from manufacturers and price considerations of payers. It’s also no surprise that this has caused a lot of complications in getting new orphan drugs approved.

We’ve got a great solution: GPI horizon – which applies an award-winning methodology to forecast your orphan drug’s value and price, so you can make sure that you’re maximizing your assets potential.

To learn more about what GPI horizon can do for your orphan asset, reach out to us below. You can also stay up-to-date with the latest GPI content by signing up to our newsletter.


Dunleavy, K. (2021). With the pricing situation ‘untenable’ in Europe, bluebird will wind down its operations in the ‘broken’ market. [online] Fierce Pharma. Available at:

Andrew McConaghie (2017). Glybera, the most expensive drug in the world, to be withdrawn after commercial flop –. [online] Available at:

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