The Italian company Molmed has fallen on news that its phase III study of Zalmoxis had failed, but it is investors in its rivals Kiadis and Bellicum that should today be asking themselves some pretty searching questions.
After all, Zalmoxis was such an economic non-starter that it was not being actively promoted, so even if its pivotal failure leads to EU conditional approval being revoked the effect on Molmed will be negligible. The bigger question is whether there is business case for any stem cell transplant adjunct like Zalmoxis; perhaps fearing the worst all three players have been trying to diversify.
This is not to deny the pressing medical need for a procedure like Zalmoxis, Kiadis’s ATIR101 or Bellicum’s Rivo-cel. Each one aims to allow stem cell transplantation to take place when only a half-matched donor is available, by reducing the risk of graft-versus-host disease.
However, while the science seems sound – the procedures use various methods to remove GvHD-causing cells, either with or without the addition of a “suicide switch” – the market reality is another story. Zalmoxis was launched in the EU in 2016, but sales were negligible, and Molmed’s marketing deal with Dompé was terminated last year.
Yesterday Molmed said an unscheduled interim analysis of its pivotal TK008 study, intended to confirm EU approval, had failed to show a disease-free survival benefit favouring Zalmoxis. Conditional approval, based on a single-arm trial in which Zalmoxis was shown to restore the immune systems of 77% of half-matched patients, now looks likely to be revoked.
|Stem cell transplant add-ons|
|Zalmoxis||Molmed||Ganciclovir/valganciclovir-triggered "suicide switch"||Conditionally approved in EU, phase III study failed|
|BPX-501||Bellicum||Rimiducid-triggered "suicide switch"; alpha/beta T cells removed||EU filing due late 2019, phase I/II in US|
|ATIR101||Kiadis||GvHD-causing cells removed using Kiadis's photodepletion tech||Filed in EU, launch due 2020; phase III in US|
|Source: Company websites.|
Meanwhile, Kiadis’s ATIR101 was filed in the EU in 2017, but CHMP questions caused a decision to be put off from the fourth quarter 2018 to the current first half; Kiadis has just delayed EU launch to next year.
Bellicum’s offering, Rivo-cel, is still expected to be filed in the EU by the end of this year, but its development was delayed by a US clinical hold. This company’s stock has been falling precipitously, standing off 40% year to date.
Of course, it might be that Zalmoxis’s problems do not indicate a broader malaise. Indeed, it has been suggested that the procedure’s approval was too narrow, its price too high and its manufacturing too cumbersome; it might be that Kiadis and Bellicum could avoid such problems.
But it cannot be denied that all three companies have already tried to diversify. Bellicum has always had a sideline in CAR/TCR therapeutics, and recently revealed a new CAR-T asset; Molmed has also got into CAR-T, and a construct targeting CD44v6 has the go-ahead to start a clinical trial.
And Kiadis recently bought Cytosen, a private company working in NK cell therapeutics (Kiadis moves to reduce reliance on its in-house lead, April 17, 2019). True, these will initially be developed as another stem cell transplant adjunct, possibly in combo with ATIR101, but one idea is that they might lead to cancer therapeutics – a hope backed by the appointment of Dr Carl June as an advisor.
Today Molmed was initially off 20%, before recovering some losses, while Kiadis and Bellicum stock traded flat. The fact that the Italian group chose to carry out an unscheduled interim analysis suggests that it might quietly have been hoping to put Zalmoxis out of its misery, and Kiadis and Bellicum will have to work hard to avoid a similar fate.
This story was updated to reflect the latest delay to ATIR101.