Snippet roundup: Edge blunted by trial's end, but Esperion soars on bempedoic acid hopes

Welcome to your weekly roundup of EP Vantage’s snippets – short takes on smaller news items.

This week, March 26-29, 2018, we had thoughts on the following: Redx stumbles out of administration straight into a clinical hold; Edge loses its edge; Abbott blesses Bigfoot; bempedoic acid PCSK9 add-on study buoys Esperion; Novo wins cardiovascular safety label but misses on hypoglycaemia; Alere bites Abbott yet again; Ablynx’s lupus failure not the ideal pre-wedding gift to Sanofi.  

These snippets were previously published daily via twitter.

Redx stumbles out of administration straight into a clinical hold

March 29, 2018

After re-emerging from administration the UK biotech minnow Redx Pharma probably thought it had put the worst behind it. But its investors were given a nasty shock today when it revealed that the very first human subject given its new lead asset, RXC004/REDX06109, had suffered possibly treatment-related adverse events; as a result the UK regulator has halted accrual into the study, designed to test RXC004’s safety and tolerability in cancer patients. Redx’s stock crashed 60% this morning, indicating further troubles for a company that in a bizarre chain of events ended up being put into administration last year when Liverpool City Council, a UK local authority, demanded that it repay a £2.0m ($2.6m) loan. The administrators then managed to sell its lead asset, the BTK inhibitor RXC005/LOXO-305, to Loxo for $40m. This enabled Redx to resume as a going concern, focused on RXC004, a Porcupine inhibitor targeting the Wnt pathway. In its defence Redx says systemic exposure to RXC004 in the first subject was higher than preclinical trials had suggested, and hopes to resume testing the project at a lower dose.

Edge loses its edge

March 28, 2018

It should be no surprise that Edge Therapeutics shares bled away to below cash values with the termination of a phase III trial for its aneurysmal subarachnoid hemorrhage project EG-1962. After all, Edge floated in 2015 on the phase I/II data from this project, which delivers the active ingredient in the oral drug nimodipine directly into brain tissue to limit vasospasm, and the group has no other clinical assets. The phase III trial’s data-monitoring committee terminated the study for futility at an interim analysis, saying it was unlikely that EG-1962 would achieve a statistically significant improvement on oral nimodipine on the primary endpoint, which is scores on the extended Glasgow Outcome Scale 90 days after treatment. The company had hoped that delivery of nimodipine microparticles would allow for a long-acting treatment without the dose-limiting side-effect of hypotension that accompanies the oral form of the drug. Edge shares fell more than 90% in trading this morning, valuing the company at about $40m. Company executives said they would lay off employees and reduce operations to preserve a cash balance that stood at $88m at December 31, 2017.

Abbott blesses Bigfoot

March 28, 2018

Yesterday Dexcom got the US glucose monitor approval it needed to put it on an equal footing – at least technologically – with Abbott. Today it emerged that Abbott has invested in Bigfoot Biomedical, just possibly marking the artificial pancreas software developer as a potential takeover target. The latest fundraising brings the total for Bigfoot’s series B round to $55m, which the Silicon Valley group will use to develop and sell its Inject and Loop technologies. The former uses blood glucose readings to calculate how much insulin patients using pen injectors should administer, and the latter works with insulin pumps to enable a system that amounts to an artificial pancreas. US pivotal trials of both are expected this year. Bigfoot and Abbott were already collaborators: the Loop and Inject systems both employ Abbott’s FreeStyle Libre continuous glucose monitor as the sensor part of the setup.

Bempedoic acid PCSK9 add-on study buoys Esperion

March 27, 2018

Esperion is doing everything in its power to give bempedoic acid a fighting chance. Not only has a phase III trial shown the project to reduce LDL cholesterol when added to Zetia and low-intensity statins, phase II data unveiled today have also revealed signs of it being able to lower LDL when added to the more potent PCSK9 inhibitors. Today's data came from a study that enrolled 59 patients who first received 12 weeks of Repatha and then were randomised to receive either bempedoic acid or a placebo for another eight weeks. Patients in the bempedoic acid arm saw their LDL fall another 27% after initiation of the add-on treatment, while LDL rose 3% in subjects on placebo. Just as importantly, none of the patients taking bempedoic acid saw a rise in liver enzymes, a side effect seen in the first phase III trial of the project, reported earlier this month. Five more phase III trials are scheduled to read out this year. Esperion shares rose 9% in morning trading following the announcement of the data from the phase II PCSK9 add-on study. 

Novo wins cardiovascular safety label but misses on hypoglycaemia

March 27, 2018

In the annals of the pharmaceutical sector Novo Nordisk’s long-acting insulin Tresiba might go down as a good product launched at a bad time. The US FDA has agreed to add cardiovascular safety data from the Devote trial to the Tresiba label, but Novo is withdrawing its request to add data from the Switch 1 and 2 studies showing that patients who change from Sanofi’s Lantus to Tresiba experience fewer hypoglycaemic events. What Novo is left with is a label suggesting that on cardiovascular endpoints Tresiba is the equal of Lantus, and on hypoglycaemic events slightly better, but with an absolute difference that might not impress payers. Bernstein analyst Wimal Kapadia estimated that 39 patients would need to be treated with Tresiba rather than Lantus to prevent one episode of severe hypoglycaemia, which might not justify the annual price difference of $1,144. Novo had the misfortune of launching Tresiba just as payers were beginning to put pressure on prices of many diabetes medications, and Lantus’s patent expiry means competition in the form of biosimilars, notably Lilly’s Basaglar and, soon, Merck & Co’s Lusduna Nexvue.

Alere bites Abbott yet again

March 26, 2018

More than two years after Abbott announced its purchase of the diagnostics group Alere the $4.6bn deal is still proving itself to be an absolute stinker. Alere was forced to pay more than $13m last September, days before the deal closed, to settle charges relating to accounting fraud and kickbacks to foreign officials, and now Abbott is having to fork out $33.2m over allegations that Alere caused hospitals to submit false claims to federal healthcare programmes by knowingly selling unreliable point-of-care tests. The settlement also resolves a civil whistleblower lawsuit filed by Amanda Wu, formerly a senior quality control analyst at Alere, who will receive around $5.6m. According to the US Department of Justice, from 2006 to 2012 Alere sold Triage devices, intended to diagnose conditions like heart failure, acute coronary syndrome and drug overdose, despite having been told they were error-prone. Worse than the pecuniary penalty is the reputational damage Abbott continues to suffer. Almost immediately after the deal was signed Abbott tried to get out of it, and various humiliations have followed thick and fast. Naturally the settlement involves no admission of liability; even so it is hard to think of a clearer failure of due diligence in recent years.

Ablynx’s lupus failure not the ideal pre-wedding gift to Sanofi 

March 26, 2018

Even if Sanofi’s €3.9bn ($4.8bn) bid for Ablynx was never about vobarilizumab, its failure in lupus today will take some of the shine off the acquisition. It also cuts off an albeit small opportunity for Sanofi to recoup some of the money it has spent. As for vobarilizumab, flopping in lupus will almost certainly be its swan song. In 2016, the project spectacularly bombed in rheumatoid arthritis, resulting in Ablynx's partner Abbvie handing back rights in that indication. Abbvie also has options on vobarilizumab in lupus, but with the asset failing to demonstrate any dose response, and the worrying spectre of two patient deaths, Sanofi will more than likely be left holding this troublesome baby. But as Sanofi’s focus was always caplacizumab, this drug’s sales will now have to live up to even higher expectations when it is launched at the end of this year to avoid the accusations Sanofi overpaid for its new bride.

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