Generating comprehensive data in rare diseases or chronic progressive conditions, can be challenging often requiring lengthy study durations and very high investment. The European Medicines Agency (EMA) therefore considers granting early market authorisation of a product for seriously debilitating, life-threatening, or rare diseases. Given the current global climate from challenges posed by COVID-19, even more interest has been directed towards fast-tracking regulatory approval. Conditional Marketing Authorisation (CMA) is a regulatory pathway for such diseases that enables timely access to therapies.

Our question is: what are the HTA implications of launching with a CMA?

1. Among the many attributes of these products, our initial exploration was to look at the HTA outcomes for drugs with orphan or for oncology indications.

2. We wanted to take a closer look at those 40 drugs. We categorised them by their orphan designation and clinical evidence packages to see if categorisations commonly sought a CMA.

Of 40 products launched with CMA:

Among non-orphan drugs, majority of the products were for oncology indications
0% have since converted to CMA to SMA, with the average conversion being 4 years
The remaining 70% are still approved for use under CMA

+ 1 Holoclar – a highly specialised stem cell therapy that only had observational clinical studies submitted

3. We did a deep-dive into the HTA outcomes of the 40 drugs that launched via a CMA. The purpose of our analysis was to explore HTA outcomes of CMA products in indicative HTA markets.

Among the many attributes of these products, our initial exploration was to look at the HTA outcomes for drugs with orphan or for oncology indications.

HTA Outcomes achieved by oncology and non-oncology indications that launched with a CMA in FR, DE, and UK

Majority of the products not assessed by respective HTA body are very recent entrants and likely to be assessed in the near future.

In Germany, a clear majority of drugs that were assessed were given ‘not quantifiable’ or ‘added benefit not proven’ as outcomes. The majority of the outcomes are not quantifiable, which may be due to the additional clinical benefit rating in certain circumstances for orphan drugs under AMNOG.

In the UK, more favourable HTA outcomes were observed from the 40 drugs that launched via a CMA in comparison to both France and Germany. Like France and Germany, orphan drugs also achieved more favourable HTA outcomes in the UK as opposed to non-orphan drugs.

Interestingly, the most common HTA outcome in the UK was recommended via CDF, which shows that oncology drugs may be the main driver for CMA products obtaining a favourable HTA outcome. Moreover, the future prospect of an Innovative Medicines Fund for the UK may act in a similar way to the CDF for oncology drugs, opening the opportunity for non-oncology products to pursue a conditional reimbursement route.

HTA Outcomes achieved by Oncology and Non-Oncology indications that launched with a CMA in FR, DE, and UK

Building on our previous analysis of orphan drugs, we decided to take a closer look at non-oncology vs. oncology drugs. The country that exhibited a noticeable difference in non-oncology vs. oncology HTA outcomes is the UK with most drugs recommended via CDF. This proves that oncology drugs launching via a CMA achieve favourable HTA outcomes because of the special considerations of the CDF.

4. We collated the obvious key observations, and we are now prepared to ask the bigger questions.

Our information database allowed us to quickly obtain all the data we needed to complete our analysis exploring links between CMAs on the type of evidence submitted and HTA outcome.

We made five key observations.

All products with CMA were subject to the same degree of evaluation by HTA bodies as SMA. Thus, pharma companies will not be granted a less rigorous process had they already launched via a CMA.
Almost half (44%) of drugs that attained CMA status were drugs that submitted PII clinical trial data. This was expected given that CMAs are used for extraordinary situations that necessitate a drug in the market as soon as possible.
In France and Germany, new product evaluation process do not seem to disadvantage CMA drugs.
In the UK, most drugs were recommended via CDF, noting that oncology drugs launching via a CMA achieve favourable HTA outcomes. The possibility of an Innovative Drugs Fund may have implications for other non-oncological indications. The relatively large proportion of oncology treatments in this sample may be the reason why the UK seemed to grant more favourable HTA outcomes.
If the link between CMA status and HTA outcome is also supported by commercially attractive price decision, this route could be considered as an attractive strategic option alongside access pathways such as the UK’s Early Access to Medicines Scheme (EAMS) or France’s Autorisation Temporaire d’Utilisation (ATU).

Now that we have established our observations, we are now in the position to ask deeper questions. Through our observations, we are able to pinpoint criticalities that will reshape our understanding of the CMA pathway and its implications on HTA and price.

If you are considering launching your drug via a CMA or if you have an orphan drug, reach out and find out more about what we can do for you.

About the authors

Dr. Jesvin Samuel

Jesvin is an immunologist by training, and has 9 years of experience in translational research in haemato-oncology. He has successfully published in leading journals such as NEJM, Blood, and the British Journal of Haematology. Jesvin has transferred his expertise to Consulting with Access Infinity, and has managed numerous global market access strategy projects.

Marianna Reyes

Marianna graduated from the University College London with a BSc in Human Sciences, a multidisciplinary biosciences degree. At Access Infinity, Marianna works on both digital solutions and Consulting projects such as a CNS opportunity assessment and global hepatology value message development and pricing. She also has deep knowledge of Spanish and Swedish price and reimbursement systems.

BALANCING A FASTER TIME TO LAUNCH VS OPTIMAL ACCESS: CONDITIONAL MARKETING AUTHORISATION AND HTA BODIES