EU Regulatory Roundup: UK Clears People Previously Treated With Advanced Therapies to Participate in Trials
UK Clears People Previously Treated With Advanced Therapies to Participate in TrialsThe United Kingdom has revised its stance on the inclusion of people treated with advanced therapy medicinal products (ATMPs) in clinical trials. Prior treatment with a cell therapy or other ATMP used to prohibit a patient from participating in clinical trials but the UK has now relaxed its position.
UK officials changed the policy in light of the limited treatment options available to people who are failed by advanced therapies. However, the revised guidance still places limitations on when patients who relapse or progress following treatment with ATMPs can be enrolled in clinical trials. While these patients have few options, the UK is only willing to let them enroll in trials if certain criteria are met.
Clinical trials are only open to patients who have recovered from the acute toxicity caused by an ATMP and may be amenable to a new therapy. Even in these cases, officials expect sponsors to identify standard of care options and have a rationale for why the investigational drug may yield a better outcome. The UK will not accept the lack of other options as a justification for enrolling a patient in a clinical trial. There must also be a rationale for why the experimental drug may work.
The guidelines task sponsors with carefully defining the clinical trial population. If there is a lack of data on the persistence and long-term safety of the previously-taken ATMP, the sponsor should take a cautious approach to the inclusion and exclusion criteria. UK officials recommend broadening the criteria and, by extension, the trial population as positive results are accumulated.
That safety-first approach reflects the degree of uncertainty about how patients previously treated with ATMPs will respond to other drugs, particularly new cell and gene therapies. While the original ATMP failed these patients, they may still have residual biological activity or circulating CAR-T cells. Sponsors should test for such activity to mitigate the risk that the interaction between the old and new ATMPs, plus the patient’s immune system, will cause unexpected adverse events.
These interactions have implications for assessments of the efficacy of the experimental drug, too. The guidelines state sponsors should acknowledge the role the previously-administered ATMP could play in the data generated by their clinical trials.
While the UK is just liberalizing its rules, clinical trials run in other jurisdictions have already assessed the effect of experimental drugs on patients previously-treated with ATMPs. Last year, researchers published data on Pfizer’s then-experimental Besponsa in acute lymphoblastic leukemia patients, some of whom had previously been treated with ATMPs. As ATMPs come to occupy more slots in treatment pathways, previously-treated patients will represent a growing, important subpopulation.
UK Guideline
NICE Knocks Back Gilead’s CAR-T, Citing Data Limitations and High Cost
The UK’s drug price watchdog has recommended against reimbursing Gilead Sciences’ CAR-T therapy Yescarta. Officials reached the draft position after analyses of the cost effectiveness of Yescarta found it is likely to exceed the quality-adjusted life year (QALY) threshold for reimbursement.
Gilead’s own submission to the National Institute for Health and Care Excellence (NICE) found the incremental cost-effectiveness ratio (ICER) compared with salvage chemotherapy was above £50,000 ($64,000) per QALY gained, the body’s standard threshold for end-of-life treatments. When NICE’s evidence review group (ERG) tweaked Gilead’s model “to reflect its preferred basecase analysis” the QALY figure swelled to above £100,000.
The ERG analysis suggests Gilead is a long way from persuading NICE that Yescarta represents a good use of the UK healthcare budget. However, as NICE acknowledges, the accuracy of the analyses from Gilead and ERG are open to debate. Both are based on results from a single-arm trial — making the comparison with salvage chemotherapy challenging — and immature survival data for Yescarta.
These limitations forced Gilead and ERG to make assumptions, hence the big difference between their QALY figures. The accuracy of the analyses may improve if UK sources of data on the cost and effectiveness of salvage chemotherapy were used in the comparison against Yescarta.
NICE also recommended against adding Yescarta to the Cancer Drugs Fund, the fallback option for oncology drugs that fail to get its backing. The decision was underpinned by the QALY analysis. Gilead, which did not make the case for Yescarta to join the fund, could increase the chances of getting the CAR-T in the program as it gathers more survival data from its ZUMA-1 trial.
The draft recommendation is open for comment until 18 September. NICE will meet to discuss the feedback on 27 September. The watchdog published the draft recommendation the day after the European Commission approved Yescarta.
Draft Recommendation, Press Release
UK Government Reassures Blood and Organ Sectors About the Impact of Brexit
The British government has released guidance to reassure organizations that use organs, tissues, cells and blood about how a no-deal Brexit would affect their operations. Officials think the sectors will be insulated from negative effects as there is little trade in the materials between the UK and European Union.
Last year, the UK imported 22 organs from deceased donors in the EU, plus 4,000 sperm samples from Denmark and a far smaller number of eggs from elsewhere in the region. The UK is practically self-sufficient in blood and blood components, although it does import some plasma units from the EU. Exports from the UK to the EU are minimal, too.
The lack of trade between the EU and UK means the sectors are less susceptible to disruption in the event of a no-deal Brexit than other parts of the healthcare system. Even so, the total severing of ties to the EU would have some effects on organizations in the UK.
In this scenario, the UK would maintain its existing standards, enabling the internal market to carry on as normal, but organizations would need to put paperwork in place to trade with the EU. Blood exporters may need to certify that their products comply with EU standards. Similarly, organizations that import or export organs, tissues and cells from the EU will need written agreements with their trading partners. The UK thinks this will place “a minimum burden on industry.”
Organ Guideline, Blood Guideline
Swissmedic Finds Valsartan Products Available Locally Meet Quality Standards
Testing by the Swiss Agency for Therapeutic Products (Swissmedic) has found valsartan products on sale in Switzerland are free from the carcinogen that has triggered recalls around the world. The tests assessed the composition of batches that were outside of the scope of the recall.
These batches should be uncontaminated with the carcinogen, N-nitrosodimethylamine (NDMA), but Swissmedic wanted to check if the recall had captured all of the affected products. No increased levels of NMDA were detected in samples of 10 valsartan-containing medicines tested by the Swiss agency.
Swissmedic is planning further tests. These tests will assess the composition of other products that contain sartans, the class of angiotensin receptor blockers that includes valsartan. Swissmedic has asked marketing authorization holders to send samples from every batch of these drugs until further notice.
The agency is testing the batches to ensure NMDA levels are below 300 parts per billion. Batches that fail this test will be pulled from the market. Swissmedic will share details of products that pass the test to reassure consumers.
Swissmedic Notice