Following his defeat of the Chimera, mythical Greek hero Bellerophon believed himself one of the gods and therefore entitled to live on Olympus. Zeus had other ideas and sent him crashing back to Earth where he spent the rest of his life blind and broken.
The medtech and biotech company named after him seems to have followed a similar path. Bellerophon Therapeutics has lost more than half its value after a phase III trial showed that its bioabsorbable cardiac matrix failed to halt tissue damage following a heart attack. The company says it will restructure and refocus on its only other product, a hypertension therapy, but the group will now not become commercial for several years.
Other technologies, different patients
The bioabsorbable cardiac matrix, also known by the research code BL-1040, failed to hit either the primary or secondary endpoints of the 300-patient Preservation I trial, intended to provide evidence for approval in Europe. The hydrogel device was injected into the patient’s coronary artery a few days after stenting was used to treat the initial infarction (Event – BioLineRx and Bellerophon hope for a matrix revolution, May 27, 2015).
The idea is that the matrix solidifies to provide support and prevent further damage. But the results from Preservation I showed it to be no more effective than saline control on the primary endpoint of change from baseline in left ventricular end diastolic volume index at six months. There was no significant difference in adverse event rates between the groups and measures including the six minute walk test and quality of life score missed as well.
Bellerophon says it will halt further clinical development of the matrix until it has analysed the full Preservation I dataset; it will release the fruits of this analysis at the European Society of Cardiology meeting in London in September.
But it is hard to know what it can possibly hope to find, so complete is the study’s failure. On a conference call, Bellerophon’s CEO Jonathan Peacock said that in future the matrix could be used in combination with emerging tissue regeneration technologies or in a narrower patient population.
Mr Peacock pointed out that the patients enrolled in Preservation I “were the most severe of the [heart attack] patients – a patient group that was less severe could be a way forward.”
Six years later
That will take time and money. In the meantime the company is to finalise a restructuring in the next few weeks and plans to begin phase III trials of its inhaled nitric oxide therapy INOpulse in pulmonary arterial hypertension this year. Bellerophon says it has around $50m in cash which will enable it to complete this trial by early 2018.
Leerink analysts suggest that Bellerophon will now run the two phase III trials that are necessary for approval of INOpulse – one in Europe, one in the US – sequentially rather than in parallel. This cash conservation will push launch of INOpulse launch from 2020 to 2023, they wrote, adding that sales of the system, which has orphan drug status in the US, could peak in 2033 at $575m.
In addition to INOpulse, Bellerophon’s Mr Peacock said on the call that the company intends to look into acquiring or investing in “new activities” that could broaden its portfolio, though how it intends to pay for its new products is unclear.
Also affected by Preservation I’s failure was BioLineRx, which invented the matrix product and licensed worldwide rights to Bellerophon in 2009. BioLine wasted no time in distancing itself from the news, saying it had minimal impact on its business and pointing to its oncology pipeline as indicating its true value. BioLineRx’s shares closed down 22% in Tel Aviv yesterday and 18% on the Nasdaq.
Bellerophon has lost much more. Its shares were down 56% yesterday and they have lost 72% of their value since it floated on the Nasdaq in February at an offering price of $12.
And, far from having its first product on the market in 2017 as it had hoped, it now looks like it will not obtain sales until 2023. Hoping to cure heart failure – perhaps the cardiac complaint most resistant to treatment – may or may not have been hubris, but nemesis has certainly come to Bellerophon.