The US Food and Drug Administration beats the European Medicines Agency to approval of novel agents across the board, but the imbalance is even more stark in oncology, the largest therapy area, a Pink Sheet analysis found.
European approval preceded the FDA’s assent for only one of the 22 cancer therapeutics approved in the US or the European Union during 2023 and through the end of April 2024. Overall, 80% of approved novel agents were cleared in the US before the EU. (For more details, see box with links to other stories in this series.)
The 22 cancer therapies make up one-fifth of the 108 novel approvals from the FDA and EU identified by the Pink Sheet’s suite of regulatory performance trackers. The oncology share is even higher, 30%, among the 48 products that have been approved both as new molecular entities or novel biologics by the FDA and as new active substances through the EU’s centralized drugs procedure.
For the 14 cancer therapies approved in both the US and EU, the median time between approvals was 6.8 months.
The group includes two very long gaps: Servier’s Tibsovo (ivosidenib) was approved in the US 57.7 months before Europe, and Otsuka/Astex’s decitabine and cedazuridine received FDA approval as Inqovi 38.3 months before the EU approved the drugs as Inaqovi. The rest of the approvals occurred within 13 months or less.
The lone EU-first approval, BeiGene’s Tevimbra, was delayed in the US by COVID-19 restrictions in China, which precluded manufacturing site inspections. The EU approved Tevimbra almost six months before the FDA.
Ripple Effects From Project Orbis?
The FDA’s oncology center is taking aim at international inefficiencies with Project Orbis, launched in 2019 to facilitate concurrent global submission and review of anti-cancer applications.
While more than 500 applications have been submitted across the eight participating members, the EMA is not one of them. Japan’s Pharmaceuticals and Medical Devices Agency became a program observer in 2023 (Also see "EMA Will Observe Project Orbis In Effort To Increase Collaboration" - Pink Sheet, 30 June, 2023.), while the EMA began following Project Orbis conversations earlier this year. (Also see "EMA To Become Observer Of FDA’s Project Orbis Early This Year" - Pink Sheet, 8 January, 2024.)
The FDA approved six novel agents under Project Orbis in 2023, accounting for nearly 30% of US novel oncology approvals over the 16 month period in the Pink Sheet analysis. The first Orbis novel approval of 2024, Amgen’s Imdelltra (tarlatamab-dlle), occurred on 16 May, outside the timeframe. Imdelltra has not been submitted nor approved in the EU.
The EMA approved three of six novel agents included in Project Orbis, with a delay of less than a month for Roche’s Columvi (glofitamab) and Johnson & Johnson’s Talvey (talquetamab). EU approval of Pfizer’s Elrexfio (elranatamab) came 3.8 months after FDA approval.
The other three Orbis FDA approvals, AstraZeneca’s Truqap (capivasertib), Coherus BioSciences, Inc./Junshi’s Loqtorzi (toripalimab) and Takeda/HUTCHMED (China) Limited’s Fruzaqla, are pending at the EMA.
At the recent American Society of Clinical Oncology meeting, FDA Oncology Center of Excellence Director Richard Pazdur noted the “inherent degree of subjectivity” in drug reviews as a reason for divergent regulatory decisions among Project Orbis participants.
“We don’t deal with perfect applications,” Pazdur said. “There’s always some type of problem, and the more the problem is, the bigger the discrepancy is going to be in potential differences, even at whether a drug is approved or not approved.” (Also see "Project Orbis, ‘Cluster’ Calls Validate Global Regulators’ Drug Application Concerns" - Pink Sheet, 7 June, 2024.)
Later In Europe, Not Never
Most novel oncology candidate sponsors plan to seek approval in Europe even if they reach the US market first.
Eight oncologics approved by the FDA in 2023 through April 2024 have not been approved in Europe. Five of the eight have marketing authorization applications under EMA review, with Bristol Myers Squibb’s Augtyro (repotrectinib) and SpringWorks Therapeutics’ Ogsiveo (nirogacestat) joining the Orbis candidates Truqap, Loqtorzi and Fruzaqla. Iovance Biotherapeutics predicted a near-term MAA filing for Amtagvi (lifileucel).
Only ImmunityBio and Day One Biopharmaceuticals have not disclosed European filing plans for Anktiva (nogapendekin alfa inbakicept) and Ojemda (tovorafenib), respectively.
More Differences In Supportive Care Pipeline
The oncology supportive care pipeline has a less global profile than the cancer treatments. The US approved five supportive care products over 16 months, while the EU cleared two. European approval of Evive Biotech’s Ryzneuta (efbemalenograstim alfa) for neutropenia in cancer patients came 4.2 months after US approval, while Curium Pharma’s prostate cancer imaging agent Pylclari (piflufolastat F18) was cleared in the EU more than two years (25.9 months) after the FDA approved Progenics in 2021 under the name Pylarify.
Small companies account for most of the other cancer supportive care sponsors with only FDA approval. Resources and imaging technology infrastructure are likely hurdles to the overseas expansion of BioLineRx’s hematopoietic stem cell mobilizer Aphexda (motixafortide), Gamida Cell’s hematopoietic stem and progenitor cell therapy Omisirge (omidubicel), Blue Earth Diagnostics’ prostate cancer imaging agent Posluma (flotufolastat F18) and Lumicell’s intraoperative optical breast cancer imaging agent Lumisight (pegulicianine).
This analysis drew on the Pink Sheet’s suite of regulatory tracking tools, including the US FDA Performance Tracker’s Novel CDER Approvals, Novel CBER Approvals and User Fee Goal Dates charts and the European Performance Tracker’s EU Approvals and EU CHMP Opinions & MAA Updates charts.
