Regado pays steep price to avert full phase III cost

If there is a silver lining to Regado Biosciences’ dark cloud it is that the group will not have to tap its investors for the full cost of a phase III trial of its blood-thinner Revolixys. This will come as cold comfort to the New Jersey company, which saw its shares plunge another 60% yesterday after enrolment in the Regulate-PCI trial was halted over serious adverse events.

Regado is now firmly an early-stage cardiovascular drug developer, which befits its shrunken market capitalisation just one year after a $43m initial public offering. The investment case relies on the thin hope that the Revolixys adverse events can be resolved, and the patience to see if REG3 shows enough promise to advance into the clinic.

Falling before the first hurdle

Recruitment in Regulate-PCI had been suspended on the recommendation of its data and safety-monitoring board’s recommendation after reports of allergic adverse events (Forget the binary outcome; Regado faces a bigger problem, July 3, 2014). This came after enrolment of 3,234 patients, just short of the 3,300 required to trigger a first interim review, an event that had the potential to clear the project of safety worries stemming from known allergic events.

The study was of Revolixys against The Medicines Company’s Angiomax in patients undergoing a cardiac stent implantation. Angiomax is used to prevent cardiovascular events following the percutaneous procedure. Strictly speaking, Revolixys comprises two drugs, an IV form of the pegylated anticoagulant pegnivacogin infused before procedure and an infusion of its reversal agent, anivamersen, after implantation.

The DMSB’s review of Revolixys-related events revealed that their “frequency and severity” merited shutting down the trial for good, the company reported yesterday. In a short call with investors, chief executive David Mazzo said the data would be examined to see if the cause could be identified, leaving the possibility that investigators could pinpoint subpopulations at lower risk of allergic reactions.

This is a rather thin hope, and one that clearly pushes back the development timeline significantly, as any post-hoc analysis would probably require confirmation in smaller trials before attempting to expand into a pivotal programme.

The news is also a blow to Regado’s other clinical project, REG2, which consists of a subcutaneous version of pegnivacogin with IV anivamersen, being tested for prevention of venous thromboembolism.

Should no regulatory path be found for either, the next best is REG3. This, like Revolixys and REG2, is a two-drug combination aimed at balancing coagulation and reversal; in the case of REG3, it comprises a glycoprotein VI (GPVI) inhibitor, RB571, with the matched control agent RB515.

The company has said that REG3’s initial indication would be diabetic vasculopathy. In the conference call yesterday executives gave no sign of when REG3 or any other pipeline project might move forward, other than to say that this would happen “as is appropriate”.

Back to basics

The company has now shrunk by more than 80% since the initial announcement of the Regulate trial’s suspension, and now stands at a market capitalisation of $95m, leaving little room for fundraising, although its commitment to an expensive 13,000-patient clinical programme has now been averted.

This will extend the cash runway substantially. The $73m it held at June 30 was never going to be able to fund Regulate fully, of course, but as Regado now is more or less a preclinical company the money will last quite a lot longer. Some expenditure will be necessary to shut down clinical sites for Regulate as well as prepare the data analyses necessary for regulatory review; beyond that, however, the company will have a “bare bones structure”, its finance chief, Don Elsey, told investors.

This combination of events can hardly be described as good news, however. Regado is justifiably valued at slightly above its cash levels, and this will only change with signs of clinical progress.

To contact the writer of this story email Jonathan Gardner in London at [email protected] or follow @JonEPVantage on Twitter