MEI would be pushing its luck to plough on with pracinostat

With a 70% plunge in market value yesterday MEI Pharma has consolidated its position as one of the few companies to fail to make progress in this roaring biotech bull market. This is for a very good reason: its lead asset, pracinostat, looks destined for the scrap heap.

Continuing with the project would be a bold move, although the fact that the company raised $46m from investors last December, in the wake of underwhelming data at ASH, illustrates just how forgiving the markets have become. The abject desertion of investor support this time, however, suggests that even MEI might be pushing its luck if it chooses to plough on.

Results released yesterday were from the largest study conducted to date with pracinostat, an HDAC inhibitor. The double-blind, placebo-controlled study recruited 102 patients with previously untreated, high-risk myelodysplastic syndrome (MDS), who were treated with pracinostat plus azacitidine – Celgene’s off-patent hypomethylating agent Vidaza – or azacitidine plus placebo.

No difference in the rate of complete remission was seen between the two arms – the trial’s primary endpoint. Further data are awaited on secondary endpoints, including duration of response and progression-free survival, while subsets will also be scrutinised, the company said.

The result appears to be definitive, however, and lays bare the danger of drawing conclusions from small investigative studies. The trial was started after a pilot study of the combination had shown an overall response rate of 89%, or eight out of nine patients, including seven who had achieved a complete remission.

Learning the lesson

In its announcement yesterday MEI also emphasised “significant clinical activity” in an ongoing, open-label, single-arm study of pracinostat and Vidaza in a second setting: elderly patients with newly diagnosed acute myeloid leukaemia (AML). About a third of MDS patients progress to AML.

Earlier this month at an investor conference the company updated data previously presented at ASH: the number of patients achieving the primary endpoint was upped from from 15 to 17, or 45% to 52%.

At that presentation the company declared the data to be supportive of moving into phase III, and it went on to describe the proposed design of a 450-patient front-line AML study pencilled in to start in June.

That tone has now been moderated, with yesterday’s press release stating that no further studies of the combination would start until MEI has “a more complete understanding of the totality of clinical data”. Having failed to confirm the earlier signal in MDS, MEI appears to have finally learned a lesson.

Cash runway

Conserving cash will now be at the forefront of the minds of executives, who are no doubt glad they raised money while they could. With MEI's market cap of $64m and cash of $79m, the chances of that being topped up in the near future are zero.

The company will struggle to justify why further cash should be spent on the pracinostat, however; a decision is likely to emerge in the coming months, after presentation of full datasets. The MDS trial had been pencilled in for Asco, although this has yet to be confirmed, while the AML study has been submitted to the European Hematology Association annual meeting in June.

The history of the HDAC class does not lend much support. Three have been approved to treat refractory patients in rare lymphomas CTCL and PTCL, and in February Novartis’s Farydak got a green light in the US in multiple myeloma, in a third-line setting. However, little convincing evidence has been generated to suggest that the epigenetic mechanism of action through which these drugs work will be useful in more valuable front-line uses.

Of course MEI would not be the first to push on with a tainted molecule, armed only with unconfirmed signals from hastily defined subsets. But its current valuation suggests that even in this market investors would not support this course of action.

A look further down its pipeline reveals only very early-stage programmes, meaning the company is facing the very real prospect of having to go right back to the drawing board.

Pracinostat studies
Front line MDS  NCT01873703
Newly diagnosed AML NCT01912274

To contact the writer of this story email Amy Brown in London at AmyB@epvantage.com or follow @AmyEPVantage on Twitter

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