Europe vs the US: New drug product approvals

For the past four years, NDA has analysed new drug approvals in the EU and the US. This year the company continued to review the publicly available data on product approvals for 2016 as reported on the FDA and the EMA websites in January 2017. In summary, the FDA had a significant drop in approvals in 2016 compared to 2015 but continues to grant more expedited and nonstandard review approval status compared to the EMA. The US drop in approvals for 2016 is not observed in the EU but is likely to be more prominent in the EU during 2017. The trend where many companies first seek approval in the US persists. Big pharma continues to dominate the approval statistics, with oncology being the most common therapy area represented.

There has been a drop in US approvals but a similar trend has yet to be seen in the EU

Last year there were a total of 74 new drug approvals granted in the US and EU together that meet our selection criteria. Of these new products, 19 were approved only in the EU, 19 only in the US, and 36 were granted in both regions during 2016. We found that 17 drugs that were approved in the EU in 2016 had already received approval in the US in 2015 or earlier, while only six products registered in the US in 2016 were approved in the EU before 2015 or earlier. This indicates that applying for approval in the US prior to registration in the EU still remains a regular practice. Compared to 2015 there is an overall drop in approvals for the US in 2016. In the EU, this decrease is not yet observed, but it’s likely that there will be a similar trend for the EU in the approval figures for 2017. Of the new drug approvals, 35 products were classified as novel drugs (eg NAS, NME or BLA), nine of these were approved only in the EU, nine only in the US and 17 were approved in both regions. For the EMA, the number represents the fewest NAS approvals since 2011, while the FDA has not approved this few NMEs/BLAs since 2010.

Expedited drug development and nonstandard review approval pathways are the new norm in the US, but in the EU special approval procedures are not as common. During 2016, special approval procedures like conditional and accelerated approval pathways were issued for seven of the new approvals in the EU, the majority in oncology and for orphan diseases. To support early drug development and speed up the evaluation and approval process, the EMA has encouraged the industry to seek early interaction via scientific advice with the regulatory and health technology assessment (HTA) bodies, as well as interactions with the Committee for Advanced Therapies (CAT). The intention is to enable early and continued interaction and dialogue between the pharma industry and regulators. In the first quarter of 2016, the EMA launched a scheme for PRIority MEdicines (PRIME), to optimise development plans and provide accelerated assessment for medicines that are of major interest for public health. Furthermore, in the last quarter of 2016 the EMA launched a new pilot for tailored scientific advice for biosimilars. The result of these efforts is still to be seen.

In the US the continued dialogue with companies throughout development offered by the FDA enables familiarity with the product at the time of registration. In 2016 special approval pathways and designations like Fast Track, Breakthrough, Accelerated Approval and Priority Review were used for 18 of the new approvals; in many cases more than one of these pathways was granted per product. Interestingly, the drop in the US approvals seen in 2016 could possibly be explained by the increased use of the shorter nonstandard approval pathways, since there has also been a significant increase in complete response letter (CRL). During 2016 the FDA issued 14 CRLs, compared to just two in 2015. According to John Jenkins, retiring director of the FDA’s Office of New Drugs, the primary deficiency in several of the applications was failure to comply with the FDA’s current Good Manufacturing Practice (cGMP) regulation: “2016 may serve as a reminder to sponsors that all of their manufacturing facilities must be in compliance with cGMP regulations if they wish to ensure approval of their application. Failure of manufacturing facilities to pass FDA inspection can unnecessarily delay patient access to novel new drugs.” The increase of CRLs seen in 2016 indicates that the use of speedier nonstandard approval pathways in the US may not be so speedy after all, at least not for 2016, as some companies have discovered. It should however be noted that the FDA has a higher rate of granting special approval status than the EMA and that the measures taken by the FDA with the introduction of shorter nonstandard approval pathways has a clear overall effect on shortening the mean approval timelines.

Oncology and big pharma dominate the approval statistics

Looking at the therapeutic areas, the busiest by far was oncology. Among the noteworthy approvals are Lartruvo (for the treatment of soft tissue sarcoma, approved in the EU and US), Rubraca (for the treatment of ovarian cancer, only approved in the US), Tecentriq (for the treatment of urothelial carcinoma, only approved in the US), and Venclexta (for the treatment of chronic lymphocytic leukaemia, approved in the EU and US).

In the US, five biosimilars were approved in 2016. In the EU, eight new approvals for biosimilars were recommended for approval by the CHMP in 2016; four of these were still pending approval by the European Commission (EC) in January 2017 (compared to no biosimilars gaining EU approval in 2015).

Altogether 39 orphan drugs were approved in the US during 2016 and 14 in the EU (a mix of NME, BLA, NAS or old substances with a new use for an orphan disease). Among the noteworthy orphan approvals are Exondys 51 (for the treatment of Duchenne muscular dystrophy, only approved in the US), Darzalex (for the treatment of multiple myeloma, approved in the US 2015 and in the EU 2016) and Spinraza (for the treatment of spinal muscular atrophy, only approved in the US). We expect the strong overall trend for more orphan drugs submitted to and approved by the FDA and the EMA to continue. In the last ten years both the FDA and the EMA have received orphan drug designation requests at record rates for each following year and this trend is reflected in the drug approvals from the agencies.

Two Advanced Therapy Medicinal Products (ATMP), Strimvelis (for the treatment of severe combined immunodeficiency) and Zalmoxis (for the treatment of certain types of high-risk haematological malignancies), were approved in the EU.

The pooled statistics show that big pharma represented 53% of the new approvals in 2016 vs 47% of the new approvals originated from small and medium-sized pharma. For big pharma it’s a decrease compared to previous years, when it contributed 72% of the new approvals in 2015 and around 64% in the two previous years. In the US several big pharma companies that did well in 2015 and the years before that did not receive any drug approvals in 2016. Both the EU and the US show an increase in approvals from small and medium-sized pharma compared to previous years but big pharma still dominates the drug approval statistics, indicating that big pharma is continuing its efforts to acquire small and medium-sized pharma with promising portfolios but without adequate resources to pull through the costly late stage drug development. One of the factors contributing to cost challenges for small and medium-sized pharma lies in the two agencies’ sometimes divergent approach in assessing benefit/risk profiles, causing the need for larger clinical trials, label differences and some drugs ultimately not reaching certain markets.