Lilly’s Sarcoma Drug Lartruvo Latest To Test EU Conditional Approval System
Executive Summary
Lartruvo, Lilly’s new drug for the rare condition soft tissue sarcoma, has been recommended for conditional marketing authorization in the EU pending the results of an ongoing Phase III study. The conditional approval system itself is under scrutiny regarding the fulfilment of obligations.
The latest drug to receive a recommendation for conditional marketing authorization (CMA) from the European Medicines Agency is a new treatment for soft tissue sarcoma, Lilly’s Lartruvo (olaratumab), which when used with doxorubicin has been shown to improve survival compared with the older drug alone.
Eli Lilly & Co. said that the opinion from the EMA’s scientific committee, the CHMP, was “the first regulatory step in the world towards approval for olaratumab,” and that that this was also the company’s first ever conditional approval recommendation in the EU.
The EMA will be watching carefully to see whether Lilly produces the data it has agreed to provide in return for getting the conditional approval opinion, not least because the CMA mechanism is itself under close scrutiny in light of suggestions that it is not working as intended.
Lartruvo is a human IgG1 MAb and an antagonist of platelet-derived growth factor receptor-alfa expressed on tumor and stromal cells, which according to Lilly means it may cause anticancer activity by targeting tumor cells directly as well as the cells that surround and support tumor growth.
The EU submission was based on data from JGDG, a Phase II, open-label randomized trial comparing olaratumab, in combination with doxorubicin, with doxorubicin alone. Efficacy endpoints included progression-free survival, overall survival, and objective response rate.
Lartruvo is clearly of great scientific interest to the EMA: as well as gaining an early recommendation through the conditional approval mechanism, the drug was granted orphan status in February 2015, and was reviewed by the CHMP under the accelerated assessment mechanism, which is used for drugs considered to be of major public health interest, particularly from the point of view of therapeutic innovation.
Assuming the drug is granted a CMA by the European Commission – which would be expected two to three months after the CHMP recommendation – it will be marketed for adults with advanced soft tissue sarcoma that has not responded to treatment with radiotherapy or surgery and who have not previously taken doxorubicin.
Approval Conditions
As a condition of the CHMP approval recommendation, Lilly will need to provide results from the ongoing Phase III ANNOUNCE study, whose estimated study completion date, according to clinicaltrials.gov, is February 2019.
Until the full data from the trial are available, the CHMP will review the product’s benefits and risks on an annual basis in order to determine whether the CMA can be maintained, Lilly said. Once the obligations in the CMA have been met, it can be converted into a full marketing authorization. This aspect of the product’s dossier will no doubt be closely monitored to ensure the company honors its obligations.
The conditional approval system came under the spotlight earlier this year when an official from the commission said it was important to ensure that companies actually fulfilled the “specific obligations” they agreed to at the time of the CMA.
Speaking at Informa's EU Pharma Law Forum in Brussels in May, Florian Schmidt of the pharmaceutical unit in the commission's health directorate also noted that while a conditional approval can be withdrawn if the company fails to meet its obligations, this has never happened in practice. He said that about half of the products with a CMA had had the deadlines for meeting the obligations changed because the companies said they were not able to meet them in the agreed timeframe. (Also see "EU Conditional Approval Should Be A Drug Development Tool, Not A Rescue Remedy " - Pink Sheet, 2 Jun, 2016.)
Concern about the CMA had earlier been expressed by the commission’s Pharmaceutical Committee, which in 2014 raised issues such as failure to fulfil post-authorization commitments in a timely manner so that the data “lose their value for regulatory purposes,” and a shortage of clinical and cost effectiveness data from real-life settings.
Similar concerns were flagged by the Council of the EU in its “Conclusions on strengthening the balance in the pharmaceutical systems in the EU and its member states,” published in June this year. (Also see "'Skyrocketing' Drug Prices, Access And Availability In Line For EU Scrutiny" - Pink Sheet, 20 Jun, 2016.) Among other things the council said there were “indications that the post-market compliance with certain obligations for marketing authorization holders is not always optimal,” which might mean that “independent research data and information from patient registries are often not structurally generated, collected and made available for research and proof of effectiveness and safety.”
Results Submitted To US FDA
The results of the Phase II study of olaratumab have also been submitted to the US Food and Drug Administration, which appears similarly impressed with the drug and granted it priority review status in May this year, having already awarded it a number of other designations, including breakthrough therapy, fast track and orphan drug.
Breakthrough therapy designation is designed to accelerate the development of a new drug intended for a serious condition where preliminary clinical evidence indicates that it may show substantial improvement over available therapies on a clinically significant endpoint.
From the editors of Scrip Regulatory Affairs.