Welcome to your weekly roundup of EP Vantage’s snippets – short takes on smaller news items.
This week, April 9-13, 2018, we had thoughts on the following: Icer sets a marker for new migraine injections; Bellicum controls damage from US clinical hold; Cymabay itching to challenge Ocaliva; FDA limits Essure sales further still; Newlink’s pivotal delay could be blessing in disguise; Merck tightens grip on first-line lung cancer; thrombosis worries ease for upadacitinib.
These snippets were previously published daily via twitter.
Icer sets a marker for new migraine injections
April 12, 2018
Amgen and Novartis’s Aimovig and Teva’s fremanezumab could come close to meeting cost-effectiveness guidelines, with a big if. In developing a draft report on the two, the Institute for Clinical and Economic Review’s (Icer's) assessment assumed that the two CGRP-blocking monoclonal antibodies would cost $8,500 a year, since they have yet to be approved and the companies have yet to disclose a price. Icer assumed that patients being treated with the CGRP projects would have already failed on up to two preventive treatments like Topamax or amitriptyline, and then compared the cost of the CGRP agents to no treatment or Botox injections. At the assumed price against no treatment in chronic disease, Aimovig cost $134,900 per quality adjusted life year (Qaly) and fremanezumab $183,600 per Qaly; compared with Botox, the costs were $147,200 and $315,100 per Qaly respectively, Icer said. Assuming that insurers’ willingness-to-pay threshold is $150,000 per Qaly in chronic migraine, $8,500 a year is an acceptable annual price for Aimovig even compared against Botox, but fremanezumab would need to be reduced to $6,100. If the threshold is $100,000 in that comparison Aimovig would need to be reduced to $6,900 and fremanezumab to $5,400 annually.
Bellicum controls damage from US clinical hold
April 12, 2018
Bellicum Pharmaceuticals can resume enrolment into the US clinical trial of its allogeneic stem cell transplant procedure BPX-501 now that it has agreed new protocols and monitoring and managing neurological events proposed by the FDA. Resolution of the hold less than three months after it was implemented is excellent news for investors, though it sheds little light on the role of Bellicum’s “off switch” in managing side effects. The trial had been suspended after reports of encephalopathy, three of which were related to treatment with BPX-501 and one of which resulted in a patient’s death. Shares climbed more than 20% in post-market trading on Wednesday, returning to levels last seen before the clinical hold.
Cymabay itching to challenge Ocaliva
April 11, 2018
Cymabay Therapeutics looks like it has a project that can compete with Intercept Pharmaceuticals’ Ocaliva in primary biliary cholangitis. Phase II data released at the Easl liver disease meeting in Paris showed that at 26 weeks the PPAR-delta agonist seladelpar reduced alkaline phosphatase levels to 1.67 times the upper limit of normal, a level that limits the risk of death or liver transplantation, on a par with Ocaliva. Seladelpar, meanwhile, was not associated with the pruritus side effect that has been reported by up to 70% of patients treated with Ocaliva in clinical trials. Cymabay so far has data from 42 patients at 26 weeks, while Intercept had results from 216 over 12 months, so seladelpar still has much to prove. Nevertheless, the data were enough to push Cymabay shares up 16% in mid-day trading today, while Intercept’s fell 6%. Cymabay plans to advance seladelpar into phase III studies later this year.
FDA limits Essure sales further still
April 10, 2018
In the pantheon of poorly thought through medtech acquisitions Bayer’s $1.1bn purchase of Conceptus in June 2013 must have a fairly prominent position. The German group bought Conceptus for its main technology Essure, used for permanent but reversible sterilisation of women – but Essure was embroiled in controversy almost immediately. A campaign against the device was launched by consumer advocate Erin Brockovich in October of the same year after several reports of pain and injury by women who had received the implant, a metal coil placed in the fallopian tubes via a catheter. Since then, the US FDA ordered Bayer to conduct a post-market study and then added a boxed warning to Essure’s label, causing US sales of the product to slide 70%. Reports of adverse events have snowballed since, and now the FDA has imposed what it calls “a unique type of restriction” on sales of the Essure device, whereby healthcare providers must go through a brochure setting out the risks of Essure with the patient, and both parties must sign the document. Analysts stopped forecasting sales for Essure some years ago, but back in 2015 the device had been forecast to have 2020 sales of $677m. Sales of that order would have justified a billion-dollar takeover; as it is, Bayer’s buy was not a smart one.
Newlink’s pivotal delay could be blessing in disguise
April 9, 2018
The future of Newlink Genetics is in doubt after last week’s blow-up of a rival IDO inhibitor player, Incyte. But things could arguably be worse. At least Newlink might now be able to abandon the phase III trial of its IDO contender indoximod – enrolment into the randomised portion of the Indigo301 study had been delayed, and thsi now looks like a blessing in disguise. That trial had planned to evaluate indoximod in combination with either Merck & Co’s Keytruda or Bristol-Myers Squibb’s Opdivo in melanoma – drawing parallels with the Echo-301 study of Incyte’s epacadostat, which flopped last week. Stifel analysts note that Newlink, which had $158m in the bank at the end of 2017, is not fully funded to complete Indigo301. It is also unclear what will happen to the planned phase II Indigo201 trial in pancreatic cancer, testing indoximod alongside Astrazeneca’s Imfinzi, which was due to begin enrolment this half. Newlink is not saying much, but made the unusual step of announcing the review of its clinical programmes. The company’s other assets also target IDO, so presumably it would need to buy in new projects to continue.
Merck tightens grip on first-line lung cancer
April 9, 2018
A win for Merck’s Keytruda as a single agent in all PD-L1-expressing first-line non-small cell lung cancer patients once again puts pressure on Bristol-Myers Squibb’s Opdivo and Roche’s Tecentriq to generate strong data for their combination regimens. Without revealing numerical results, Merck this morning announced that Keytruda in the Keynote-042 trial had shown an overall survival benefit against platinum-based chemotherapy in patients with PD-L1 expression on as few as 1% of tumour cells. As a monotherapy in first-line treatment Keytruda currently can be used in patients with 50% PD-L1 expression, and Keynote-042 could extend its reach to 70% of patients who have never been treated, Bernstein analyst Timothy Anderson wrote today. With Bristol and Roche set to release data from their first-line chemo combo trials with Opdivo and Tecentriq respectively at next week’s AACR, the discussion at that meeting will shift to whether the gains shown by those two regimens can be achieved with lower toxicity and cost with Keytruda monotherapy, Mr Anderson wrote.
Thrombosis worries ease for upadacitinib
April 9, 2018
Beating Humira in a head-to-head rheumatoid arthritis trial is only half of the positive news coming from Abbvie’s trial of its follow-up, upadacitinib. The other half is that safety data appear to confirm what Abbvie had been insisting all along – that the risk of thrombotic events among patients taking upadacitinib was no greater than the background rate in rheumatoid arthritis. The Select-Compare trial found two instances of thrombotic events among the 651 patients taking upadacitinib, versus three in the 327-patient Humira arm and one in the 651-patient placebo arm. The primary efficacy analysis compared a once-daily 15mg pill of upadacitinib against placebo on the ACR20 score – a 20% improvement in disease activity – at week 12, which was reached by 71% of upadacitinib patients and 36% of placebo recipients, a significant difference. A secondary analysis of upadacitinib against the standard Humira dose of 40mg every other week found that the oral drug was statistically superior on ACR20, 50 and 70, as well as on clinical remission and low-disease activity measures. Abbvie shares rose 3% in morning trading today.