Seeking Alpha
Profile| Send Message|
( followers)  

The developmental and regulatory minefield confronting companies attempting to develop follow-on-biologics (FOBs), or biosimilars, was highlighted again this week with Merck's (NYSE:MRK) decision to scrap development of MK-2578, its pegylated form of erythropoietin similar to Amgen’s (NASDAQ:AMGN) blockbuster anaemia drug Aranesp.

MK-2578 was widely expected to be the first biosimilar erythropoietin-stimulating agent (ESA) onto the US market with a launch pencilled in for 2012. However, the FDA has requested cardiovascular outcome data for the product, which Merck believes will be too onerous and lengthy to be worth it. Perceived by some in the market as good news for Affymax through the removal of a key competitor to its own ESA agent, Hematide, the FDA’s stance on cardiovascular safety for these products could set alarm bells ringing at the Californian biotech ahead of crucial phase III data.

FOB or BLA?

The FDA’s request for extensive clinical safety data on MK-2578 is indicative of the major regulatory hurdles that biosimilars will have to clear to gain approval, even if this particular example is complicated somewhat by changes in the regulatory and commercial landscape for ESAs (Cardiovascular risk prompts new US scrutiny of Epo drugs, March 25, 2010).

As a pegylated version of Aranesp, developed using a sugar modification technology that Merck obtained through its $400m acquisition of GlycoFi in 2006, in reality MK-2578 was being developed as a so-called ‘bio-better’.

As such, considering the clinical and toxicology work involved and potential to differentiate its product, Merck intended to use the current BLA route to regulatory approval instead of the new biosimilar pathway available since healthcare reform legislation (BIO 2010 - Biosimilar pathway cleared in US but will any company set foot on it?, May 6, 2010).

So far the bigger players have plumped for the BLA route for their biosimilar products, Teva (NYSE:TEVA) for example recently filed a full BLA for Neutroval (XM02), a similar agent to Amgen’s neutropenia drug, Neupogen (Teva and Amgen shaping up for vital biosimilar fight, February 3, 2010).

In fact, Merck will be watching the regulatory progress of Neutroval very closely given that its only biosimilar products now in clinical development are MK-4214 and MK-6302, similar versions of Neupogen (filgrastim) and Neulasta (pegfilgrastim) respectively. Amgen recorded combined US sales of $3.43bn last year for these granulocyte colony stimulating factor (G-CSF) products.

Meanwhile the FDA's stance that prompted Merck’s decision to scrap MK-2578 could affect Teva’s plans to file its biosimilar ESA in the US, which it obtained through the recent acquisition of Ratiopharm; the German generics group launched Eporatio in Europe last November.

Good or bad news for Affymax?

Hematide is a synthetic peptide-based ESA, in contrast to the recombinant protein ESAs already on the market such as Aranesp and Epogen. Affymax hopes the long-acting properties of Hematide will offer a more convenient dosing of once every four weeks, compared to sometimes multiple times per week with current ESAs, while also being safer.

Data from multiple phase III trials are expected shortly, comparing Hematide to both Aranesp and Epogen (Event - Expectations high for Hematide phase III data, but bundled payments await, February 17, 2010).

As well as comparing efficacy outcomes, Hematide’s cardiovascular safety profile will be assessed by pooling cardiovascular events across all the studies. Given the FDA’s increasing concerns about the safety of ESAs, the fear must now be that the regulator asks for further cardiovascular outcome data even if the current trials hit their efficacy and safety endpoints.

Source: Merck's Ditching of Aranesp Biosimilar Highlights Follow-on-Biologics Pitfalls