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Endocyte diagnoses companion in Merck to set precedent!

Authored by Karl Simpson

The area of companion diagnostics is very hot right now. As the industry strives towards the goal of personalised medicine and therapies, many companies are looking at the opportunities that arise from using technologies like imaging agents.

Endocyte is one such company effectively using companion diagnostics. In 2012, Endocyte managed to broker a deal with Merck (MRK) for its lead drug candidate vintafolide indicated for platinum resistant ovarian cancer. Endocyte received $120m upfront and becomes eligible to receive milestone payments of up to $880m linked to development goals, regulatory outcomes and ultimately commercialisation for vintafolide in ovarian cancer and multiple other indications too, such an non-small cell lung cancer.

Endocyte is a company which develops small-molecule drug conjugates (SMDC) which screen diseased cells for unique receptors. Once that receptor has been identified, they target the ligand which binds to the target receptor. This targeting ligand is then attached to a diagnostic imaging agent and tested to demonstrate that in humans the SMDC targets the correct diseased cells and not normal cells.

Endocyte received significant interest from across the sector for its ventafolide product and underwent numerous discussions and due-diligence over several months before agreeing on partner Merck. What adds interest is the way this deal is structured and the fact that Endocyte retained all the rights to the companion diagnostic etarfolatide. CEO Ron Ellis admitted this was something the company was very keen to retain so that the agent could be used to develop other products outside of the Merck agreement. Clearly what it also does is keep Endocyte a very important part of the alliance between the two companies as the imaging agent is a critical part of the therapy and any regulatory approval.

The regulatory challenges associated with this combination approach are incredibly complex. Endocyte chose to go the European route because the EMA were more receptive to looking at the data than their FDA counterparts who were more focused on Overall Survival (OS). Endocyte have achieved EMA orphan drug status for Endocyte’s folic acid solution for ovarian cancer. The solution is used as a pre-injection for the imaging agent to bring more accurate diagnosis and block out the white noise which disturbs image quality. The imaging agent, etarfolatide, then identifies tumour cells which over express folate receptors. An estimated 80% of ovarian cancer patients have been proven to have folate receptor-positive disease.

Despite the relative willingness on the EMA to look at this companion diagnostic and therapeutic approach, there were some considerable regulatory challenges which centred on the simultaneous nature in which the folic acid and diagnostic agent were presented together. What this underlines, without going specifically into the regulatory issues, is that the regulatory bodies of the FDA and also the EMA are behind the curve in terms of having clear regulatory frameworks for what will be an ever growing number of companion diagnostic products that will be very complex in nature. This will require very innovative and creative regulatory approaches to ensure the diagnostic products, for which there might be more than one component, arrive in the clinical setting without adding to the existing challenges of physicians.

Acceptance of the EU regulatory filings for vintafolide and etarfolatide triggered a $5m milestone from Merck and market expectation is for a regulatory conditional approval. Both vintafolide and etarfolatide have been granted orphan drug status by the European Commission. The regulatory submission is for folate-receptor (FR) positive platinum-resistant ovarian cancer. The data underpinning the filing is from their 149-patient PRECEDENT trial, which demonstrated a 2.3mth increase in PFS but no OS benefit. Ventafolide is currently being studied in a phase III trial (PROCEED) for ovarian cancer and a Phase II for non-small cell lung cancer.

Endocyte is not solely focused on the vintafolide product at this stage and in January 2013 announced it had achieved key objectives in a Phase 0 study of EC0652, a diagnostic imaging agent targeting prostate specific membrane antigen (PSMA), a protein expressed on cancer cells originating from the prostate as well as on tumour neovasculature. They intend to file an IND for the corresponding therapeutic product EC1069 by the end of this year.

With a current market capitalisation of $340m, the company has really seen a recent boost to its value but with regulatory approvals and new clinical data, the company seems to be in a very good position to advance its technology platform further and increase value. Endocyte are a very good example of how companion diagnostics are becoming a real advantage in treating cancer and many other diseases through personalised medicine, which is why Endocyte are already extending their programmes into inflammation, viral infections and other indications. They are certainly an interesting company to watch, and in particular, it is intriguing to watch other companies with companion diagnostics to see how they treat their assets going into alliances.

I felt it would be good to explore the way Endocyte approached the licensing of its lead drug and companion diagnostic. In doing so, we see how Endocyte employed a strategy to optimise their regulatory outcome and their commercial value through the partnering deal. It also demonstrates the respective value companies in an alliance place on the different elements of the therapeutic and diagnostic approach. We will be seeing many more companies like this as Endocyte is just one example.

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