Vantage Snippets are short summaries of breaking news stories.
Suggesting that Nash might not be the El Dorado for which many companies are hoping, Conatus Pharmaceuticals today joined the ranks of small pharma companies nursing clinical losses. Choosing to announce the failure of the phase IIb Encore-PH trial on a day the markets are shut is a strategy unlikely to go down well with investors, however. On a conference call, Steven Mento, chief executive officer, was keen to explain that Encore-PH was just one of three trials of emricasan. He also pointed to “clinically important improvements” in patients’ hepatic venous pressure gradient, despite the changes not being statically significant, and suggested a bigger trial might have been more successful. With two trials still to read out, Conatus is already stressing that they and partner Novartis will look at the data in their totality, and pointing to what looks to be better efficacy in sicker patients. However, if emricasan fails in either of the next two trials, management’s reassurances will not be enough to soothe investors.
|Study||Disease/primary endpoint||Trial ID||Readout|
|Encore-PH||Nash with severe portal hypertension/24wk chg in HVPG||NCT02960204||Failed Dec 5|
|Encore-NF||Nash fibrosis/fibrosis improvement without Nash worsening||NCT02686762||H1 2019|
|Encore-LF||Nash cirrhosis/event-free survival||NCT03205345||Mid-2019|
After spending the last few months frantically combing through the failed pivotal study of its lead asset, Faron triumphantly announced today that it had found a signal of efficacy. Traumakine flunked the 300-patient Interest trial in acute respiratory distress syndrome back in May; the interferon-beta 1a- based therapy failed to show any difference from placebo on either ventilator-free days or mortality. The company has had to dig right down to the DNA to find what it was looking for: patients carrying a particular single nucleotide polymorphism had 5.7 times greater likelihood of survival at day 28 than those without the mutation, it proclaimed, dubbing these carriers the “optimal subgroup” for treatment. This analysis should be met with some scepticism, however. The analysis was not pre-specified, rendering the positive p values touted statistically slippery, while the small patient numbers involved are another big red flag. Faron intends to file the data with US and EU regulators early next year, which was enough for some investors to push the company’s beaten-down stock up 22%. But the very best case scenario is surely that regulators will tell Faron to run another study. With only €11m in the bank and nursing a 91% erosion in value this year, the company surely needs to unearth more than a post hoc analysis to push Traumakine forward.
If only Cerenis Therapeutics was as good at clinical development as it is at attracting industry heavy hitters to its board. The group, which has counted Glaxosmithkline’s Jean-Pierre Garnier and Merck & Co’s Barbara Yanni as board members, today announced that its lead product CER-001, an HDL mimetic, failed in the phase III Tango trial for patients with familial hypoalphalipoproteinemia. Investors reacted by sending shares in the group down 58% to just 62 cents, a far cry from the €14 they commanded three years ago. This is not the first clinical banana skin for CER-001. In 2017 the group lost 73% of its value after the project struck out in a pivotal post-acute coronary syndrome trial. With CER-001 almost certainly a busted flush, Cerenis is joining the industry R&D herd and turning its attention to CER-209, a phase I NASH asset. While jumping on the Nash bandwagon might be a smart way of keeping any remaining investors onside, the group is facing the readout of a dosing trial for CER-209 by the end of the year. If it stumbles here as well, Cerenis will be facing a miserable Christmas, and a very uncertain New Year.
Keeping well within its respiratory specialism, Resmed has bought Propeller Health, maker of sensors that attach to inhalers and track medication use by patients with asthma and early-stage COPD. The sensors communicate with an app on the patient’s phone, and thus fit in with Resmed’s other digital health initiatives, including cloud-connected ventilators and oxygen concentrators for patients with more advanced COPD. The deal is worth $225m in cash, a snip compared with the purchase – less than a month ago – of electronic health record software developer Matrixcare for $750m. Resmed seems to have a very clear picture of where its M&A strategy is targeted: its last five deals have all been either digital health and software companies or respiratory device developers. Further deals from the California medtech cannot be ruled out, particularly as investors seem to be happy; the company's market cap has doubled over the last two years, to $16bn.
|Resmed's recent acquisitions|
|Date||Target||Value ($m)||Target focus|
|December 3, 2018||Propeller Health||225||Anaesthesia & respiratory; healthcare IT|
|November 5, 2018||Matrixcare||750||Healthcare IT|
|July 9, 2018||Healthcarefirst||-||Healthcare IT|
|April 4, 2016||Brightree||800||Healthcare IT|
|February 4, 2016||Inova Labs||-||Anaesthesia & respiratory|
|Source: EvaluateMedTech, company communications.|
Presenters of Maia, the first-line multiple myeloma study of Darzalex, have defended its ability to change clinical practice even though it is still a long way from showing a survival advantage. The trial, presented in an Ash late-breaker, is vital to extend the Genmab/Johnson & Johnson drug's reach by combining it with the US-dominant backbone of Revlimid and dexamethasone. The combo’s progression-free survival benefit is considerable, with a strong effect after 30 months, but an immature overall survival analysis shows a negligible separation in the curves so far. The problem is that Darzalex is already available second and third line, meaning that progressing control-arm subjects could receive it; and, if these patients’ survival improves, the active arm’s benefit could be squeezed. Hôpital Claude Huriez’s Dr Thierry Facon, who presented the late-breaker, would not say how many control patients went on to get Darzalex or what the lack of a final OS benefit would mean for Maia, but brushed aside such concerns by stressing to Vantage that the Maia population was relatively elderly. He called Darzalex a new front-line standard of care in transplant-ineligible patients, and discussion at an Ash press briefing centred on the exorbitant cost of such a combo.
Vanda Pharmaceuticals’ December of catalysts is halfway to being a complete success, with a phase II gastroparesis trial of tradipitant having yielded positive results. The NK1 antagonist showed a 1.2-point improvement in the nausea score using the gastroparesis cardinal symptoms index and a 28.8% improvement in nausea-free days at four weeks, a statistically significant difference to placebo. Stifel analyst Derek Archila wrote that physicians would consider an improvement in nausea score of at least one-point and a 20% improvement in nausea-free days to be clinical beneficial. These data will likely draw the attention of big pharma, although gastrointestinal players like Allergan and Takeda already have their own assets. Next up for Vanda is readout of a trial of its sleep aid Hetlioz in patients with Smith-Magenis syndrome, which is also expected by the end of 2018.
|WW sales ($m)|
Diabeloop’s closed loop insulin delivery system – a basic form of artificial pancreas – has become the second to be CE marked in Europe, two years after Medtronic’s Minimed 670G. The approval was based on the 68-patient WP7 trial, in which Diabeloop’s DBLG1 system allowed patients to spend more time in the target blood glucose range, and have fewer hypoglycaemic events, than patients who used an open-loop system consisting of a standard pump and sensor. The DBLG1 itself links a glucose sensor with a patch insulin pump via a smartphone-like device hosting Diabeloop’s algorithm, which can predict future blood glucose levels and deliver insulin accordingly. Having obtained CE mark, Diabeloop will now turn its efforts towards funding, and aims to close a round in the first quarter of next year. So far it has had just one infusion of funding, €13.5m ($15.3m) in the summer of 2017. Diabeloop has previously detailed its plans to get reimbursement for the system in Europe, develop a second-generation version and ultimately seek US approval (Diabeloop takes the collaborative route to Europe, May 11, 2017). It will need a sizeable venture haul if it is to achieve all that.
Chalk up another poor Ash meeting for Spark Therapeutics. An update from a phase I/II study of its haemophilia A gene therapy candidate SPK-8011 has increased skepticism about the highest dose and suggested why the company had been unwilling to reveal detailed data from this cohort. Spark had said before Ash that it would not present detailed data from the highest dose of SPK-8011, 2x1012vg/kg, and had also said that two patients in the high-dose group had a suspected capsid immune response that led to loss of factor VIII expression. Presumably this made efficacy in the seven-patient arm look poor; in an apparent attempt to talk up the data the company did say that in the other five patients in this arm there had been a 100% reduction in bleeds. Immunogenicity has long been a concern with SPK-8011, and Spark had previously said it would address this by expanding the high-dose arm to include prophylactic steroids rather than using steroids reactively, as before. But the latest update will only increase investor jitters ahead of readout in mid-2019 – particularly as, around the same time, Spark’s haemophilia A gene therapy rival Biomarin is due to report three-year data with its candidate, valoctocogene roxaparvovec (valrox).
Alkermes has delivered a schizophrenia candidate in ALKS 3831 that looks good for regulatory approval, but the commercial case based around weight gain could be much more challenging. The second of two phase III trials, shows that the agent, a combination of the antipsychotic olanzapine with samidorphan, caused patients to gain significantly less weight than olanzapine alone. This was a co-primary endpoint in the Enlighten-2 trial. The fact that ALKS 3831 did nevertheless cause weight gain, might make it difficult for Alkermes to set a price that payers will find acceptable, since olanzapine is generic. A second co-primary endpoint, was also met with a lower proportion of patients taking ALK 3831 gaining 10% or more of body weight over baseline, compared with olanzapine. That second endpoint provides potential niche for ALKS 3831 – poaching those patients who see a rapid weight gain in the first weeks after starting olanzapine. In any case, the result was better than in the first trial of ALKS 3831, Enlighten-1, which found greater weight gain when compared to olanzapine. Alkermes shares fell 2% in early trading today.
|ALKS 3831||Olanzapine||p value|
|Average weight gain (% of body weight)||4.21||6.59||0.003|
|Percent of patients gaining 10% of body weight||17.8||29.8||0.003|
Score one for Teva and Celltrion for clinching the first US approval of a biosimilar version of Rituxan, for patients with B-cell non-Hodgkin’s lymphoma. The approval of Truxima comes seven months after the product was issued with a complete response letter owing to manufacturing concerns. But as anyone watching the US biosimilar market knows, approval is one thing and achieving decent sales is another. So far, of the seven approved biosimilar mAbs in the US only two have actually managed to launch, and both have failed to make the kind of impact that their European biosimilar counterparts have made in terms of shaking up pricing or stealing market share. Most of this, however, has been down to pricing strategies adopted by originators and difficulties in coverage and reimbursement. Indeed, the lack of progress for biosimilars in the world’s biggest drugs market has led some groups to give up entirely on their biosimilar ambitions. What might shift the dial for Truxima and Teva is the growing political and public pressure to reduce drug costs. The Democrats now control the House of Representatives, and are almost certain to be casting an eye over some of the practices employed by originators to keep biosimilars off the market. Rituxan’s US sales came to $4.2bn last year; for companies willing to hang on during what is sure to be a long process of opening up access, even a modest slice of these sales would be considered a success.
|US approved/market MAb biosimilars|
|Product||Company||Reference Brand||USA Phase (Current)||WW 2024e sales ($m)|
|Renflexis||Merck & Co||Remicade||Marketed||-|