The other shoe drops for Bellerophon

To lose one lead product may be regarded as a misfortune; to lose two looks like carelessness.

Trial Results

Three years ago Bellerophon Therapeutics suffered a nightmarish crash when its lead product, a bioresorbable cardiac matrix for heart attack patients, failed in a phase III trial. History has now repeated itself – or very nearly – with the phase III study of its new lead, a device for pulmonary arterial hypertension, being halted for futility. Bellerophon’s shares have plummeted 79% so far today.

The INOpulse system is Bellerophon’s only remaining technology, though the company is developing three slightly different versions for different types of pulmonary hypertension. The canning of the INOvation-1 study leaves the remaining trial plans, and perhaps Bellerophon itself, in a highly precarious situation.

INOpulse is a wearable system that allows pulmonary arterial hypertension (PAH) patients to inhale nitric oxide while on the go. The logic behind it is reasonable: nitric oxide is a vasodilator and inhaling it is known to have a significant effect on pulmonary arterial hypertension (PAH). But the gas has an extremely short duration of action and is highly volatile, meaning it must be breathed in more or less constantly, generally requiring a hospital setting. INOpulse was intended to set patients free.

Logic or not, it does not work. In a prespecified 16-week analysis, INOvation-1’s data monitoring committee reviewed data on the first 75 patients and found that while safety was clean, the average change in six-minute walk distance, the primary endpoint of the trial, was too small to justify continuing.

If Bellerophon’s management is disappointed analysts from HC Wainwright must be devastated. Last Thursday they wrote that the likely outcome of the interim analysis would be either a continuation of the study as designed or an early trial completion due to a significant efficacy signal.

Now what?

Over the next few weeks Bellerophon plans to comb through the data “to determine the next steps”. It said it remained positive regarding the other two indications it has pursued with INOpulse, pulmonary hypertension associated with interstitial lung disease (PH-ILD) and pulmonary hypertension associated with chronic obstructive pulmonary disease (PH-COPD).

Bellerophon's active clinical trials
Status Trial N NCT Number Completion date
Recruiting Placebo-controlled phase III trial in PAH (INOvation-1) 200 NCT02725372 December 2018
Active, not recruiting Long-term phase III extension study in PAH 22 NCT02652429 December 2018
Not yet recruiting Phase III trial in PAH  40 NCT03602781 June 2019
Recruiting Phase II trial in pulmonary fibrosis (a type of PH-ILD) 40 NCT03267108

October 2018

Source: clinicaltrials.gov.

A phase IIb trial in PH-ILD is underway, with top-line results expected around the end of 2018. A phase II PH-COPD trial is, or perhaps was, in the planning stages.

Unless something extraordinary turns up in the data dredge these programmes must surely be toast. The indications are all based on the same clinical rationale, and are so similar that if the technology fails in one it can hardly be expected to succeed in the others.

This leaves Bellerophon in a fairly dismal spot. When its matrix, BL-1040, failed it still had INOpulse as a back-up (Bellerophon suffers a glitch in the matrix, July 28, 2015). Now the cupboard is bare.

As of June 30, the company had cash of $26m. Keeping its head above water by buying in or licensing another product, for instance, seems like a long shot.

Today Bellerophon said it has sufficient resources to support its currently planned activities into the first half of 2019. After that, its future is less clear.

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