Vantage Snippets are short summaries of breaking news stories.

US authorisation arrives for point-of-care Covid-19 tests

In the past week the US FDA has granted emergency use authorisation for a further seven in vitro diagnostics for Covid-19 infection, bringing the total to 16. Smaller groups like Mesa Biotech and Avellino join relative majors including Perkinelmer and Biomérieux in gaining the agency’s backing for their tests for the coronavirus. Mesa’s technology is particularly interesting: its handheld Accula device, which got EUA on Monday, is designed to enable testing wherever the patient presents, and can give results in about 30 minutes. Still, this device will be unable to process the volume of samples that the large, high-throughput instruments from larger groups like Roche and Hologic can offer. On the same day the FDA granted an EUA for a test developed by Biomérieux's subsidiary Biofire Defense. The Biofire Covid-19 test was developed with funding from the US Department of Defense under an existing contract, and has a turnaround time of around 45 minutes. Biomérieux is working on two other Covid-19 tests, one of which is a panel intended to diagnose Covid-19 plus 21 other common respiratory pathogens. The full list of EUAs granted to date can be found here.

Bristol gets ozanimod nod, but future is less certain

Bristol-Myers Squibb's ozanimod, now trademarked Zeposia, was thought likely to creep into the top 10 best-selling relapsing/remitting multiple sclerosis drugs of 2024, EvaluatePharma consensus shows. However, these sellside forecasts were made before the coronavirus-induced global lockdown, and Bristol said it would hold off launching the product. Zeposia was always going to struggle to carve out share in a hugely competitive market, and Bristol will not be the only drug company reconsidering launch plans right now. Perhaps more concerning is the potential impact the pandemic might have on studies being conducted to move ozanimod into other autoimmune conditions; analysts expect around half of the drug's 2024 sales, of $966m, to come from uses outside MS. Four pivotal studies in ulcerative colitis and Crohn's disease are technically open for recruitment, although new patient enrolment is surely stalled for now. Holders of the Celgene CVR, meanwhile, might be celebrating the first box to payout being ticked, but Bluebird's statement today, warning of clinical delays, should give them pause. The partnered Car-T project bb21217 must also win a US green light by March 2021 for a payout to happen; Bluebird needs to stick to its promise that a filing will happen soon. 

Small companies work on Covid-19 antibody tests

Statements this week from Public Health England that the UK would soon start mass testing to identify people who have had a Covid-19 infection and recovered, and are therefore immune, have thrown the spotlight on developers of these antibody-based blood tests. Serological tests for antibodies to viruses, such as IgM and IgG, use fairly simple and cheap techniques such as enzyme-linked immunosorbent assay (Elisa). As such they could in theory be produced by many different diagnostics companies and run in almost any microbiology lab in the country. Several small companies have said they are developing these tests – including the US groups Biomerica and Chembio Diagnostic Systems, Germany’s Pharmact and South Korea’s Sugentech. As for UK companies, Surescreen Diagnostics is already selling a Covid-19 test abroad, and an assay for antibodies to the virus plus the inflammatory biomarker C-reactive protein developed by Attomarker is being tested at St Thomas’s Hospital in London. Public Health England has bought 3.5 million serological assays, but has not said from whom. Neither is it clear exactly when the screening programme will begin; the UK government has said that the tests’ accuracy must be ascertained before widespread distribution.

Regulators: Covid-19 vaccines need animal data, but not always up front

Global regulators got together this week to figure out acceptable levels of preclinical data to justify moving a novel coronavirus vaccine very quickly into human testing, and the answer seems to be: it depends. Information on closely related projects and well-characterised platform technologies can support a swift initiation of clinical work, though developers need to provide a data-backed rationale to justify why certain preclinical work need not be completed first. The working group, co-chaired by the EMA and FDA, stated animal data would be required, and the immune response characterised, although efficacy in animal challenge models need not be demonstrated before human studies commence. This preclinical work can be conducted in parallel in certain cases, but risk-mitigation strategies must be in place; the potential for vaccine-induced disease enhancement is a particular concern. A lack of suitable animal models means that requiring preclinical work to be completed before starting trials would significantly delay clinical vaccine development, the report acknowledged. Regulators are clearly cognisant of the need to move fast here – Moderna has already been allowed to test in volunteers with little preclinical proof of safety – and it seems that others will soon be following.

Leading coronavirus vaccine candidates 
Company  Project Detail 
Moderna  mRNA-1273 Currently being tested in healthy volunteers (US), NCT04283461
Cansino Biologics  Ad5-nCoV Currently being tested in healthy volunteers (China)
Biontech/Pfizer BNT162 Clinical trials due to start by end April 
Inovio  INO-4800 US clinical trial to start in April, then China and South Korea
Others pursuing preclinical work include Sanofi, Johnson & Johnson and Curevac. Source: company statements.

Pivotal readouts threatened by Covid-19 represent a $20bn investment

Last week Vantage highlighted 315 pivotal trials that are approaching readout and that could face delays caused by the new coronavirus pandemic. These studies of unapproved, novel medicines, due to end this year and seeking 172,104 subjects, represent years of invested time and money, and test some of the industry’s biggest new hopes. A further analysis seeks to put a figure on exactly how much cash is being put to work here: $20bn is the figure that EvaluatePharma Vision* estimates it will cost to run these 315 studies. Delays to much of this clinical work seem unavoidable as Covid-19 causes global lockdowns – and longer trials means more expense. This is before considering the knock to the profitability of a project, lengthening the time it takes to get to market. At this stage it is impossible to estimate the real cost of the pandemic, but the sums committed to trials detailed below illustrate what is at stake to various developers. Lilly announced a pause to much of its research work this week, and others will surely follow. Smaller companies reaching critical stages, like Satsuma and Axsome, below, will be under especially intense pressure.

Commercially sponsored pivotal trials of novel projects due to read out this year   
Stage Trial count Total enrolment  Estimated total cost of running these studies ($bn)
Active, not recruiting  147 107,248 11.75
Recruiting  168 64,856 8.45
Total  315 172,104 20.19
Source: EvaluatePharma Vision*. 


Blockbusters under threat? The costs committed to pivotal programmes approaching conclusion   
Project and trial info Company  2024e sales ($m) Estimated cost of running study/ies ($m)*
Tirzepatide: Surpass 3 trial in type 2 diabetes Lilly 1,619 130
Bardoxolone: Catalyst trial in PAH Reata 1,608 36
Sacituzumab govitecan: Ascent trial in TNBC Immunomedics 1,365 75
BMS-986165 (Tyk2 inhibitor): 4 psoriasis trials  Bristol-Myers Squibb 1,178 384
Filgotinib: Selection1 trial in UC  Gilead/Galapagos 1,031 218
Ozanimod: 4 trials in MS, UC and Crohn's Bristol-Myers Squibb 966 1112
Efgartigimod: Adapt trial in myasthenia gravis Argenx 964 29
Mirikizumab: 2 trials in UC and psoriasis Lilly 848 361
AXS-05: 2 depression trials, incl Stride-1 Axsome 753 46
Fintepla: 3 epilepsy trials, in Dravet and LGS Zogenix 694 126
*For study IDs relating to these costs please see Clinical trial delays become reality as Covid-19 risk spreads. LGS=Lennox-Gastaut syndrome; UC=ulcerative colitis; TNBC=triple-negative breast cancer; PAH=pulmonary arterial hypertension. Source: EvaluatePharma Vision. 

*EvaluatePharma Vision’s R&D cost model estimates the cost of individual clinical programmes using real-world data. Company disclosed product-level spend and clinical trial patient numbers are combined to create cost per patient benchmarks by technology and therapy type. Utilising a matching algorithm these benchmarks are applied to all commercially relevant clinical trials to estimate their cost, which can then be aggregated by product to estimate the cost of development of all products. 

Genmark adds $100m in value on Covid-19 test authorisation

The fates of companies that have obtained FDA emergency use authorisation for their sequencing-based tests for the novel coronavirus have diverged wildly, judging by their share price performance in the trading period after the EUA was granted. Top of the tree is Genmark Diagnostics, up 41% in early trade today; authorisation for its test was announced yesterday evening. Stock in Abbott, however, fell 6% yesterday, since authorisation for a single test, even one for Covid-9, will not be greatly significant for the world’s third-largest medtech group. Abbott says it will immediately ship 150,000 tests to existing customers and will scale up production to make a million tests per week by the end of this month. ​Genmark’s test works exclusively on the company’s ePlex system, which had a global installed base of more than 500 as of December 31, 2019. The ePlex machine can provide results in under two hours with the capacity to process up to 96 tests per eight-hour shift. While this is far behind Abbott’s capabilities – there are 175 of its m2000 RealTime systems in the US alone – it is highly meaningful for the tiny company. And anything that can help fight the pandemic is to be welcomed.

US FDA emergency use authorisations for Covid-19 tests 
Date of EUA Company Test  Instrument 1-day share price move
March 19 Genmark Diagnostics ePlex Sars-CoV-2 Test ePlex system 41%*
March 19 Diasorin Molecular  Simplexa Covid-19 Direct assay Simplexa Direct 8%*
March 18 Abbott Molecular RealTime Sars-CoV-2 assay m2000 RealTime -6%
March 17 Quest Diagnostics Sars-CoV-2 rRT-PCR Applied Biosystems 7500 0%
March 17 Quidel Lyra Sars-CoV-2 assay Applied Biosystems 7500 26%
March 16 Labcorp Covid-19 RT-PCR test Applied Biosystems QuantStudio7 Flex 2%
March 16 Hologic Panther Fusion Sars-CoV-2 assay Panther Fusion 1%
March 13 Thermo Fisher Scientific TaqPath Covid-19 Combo Kit Applied Biosystems 7500 5%
March 13 Roche Molecular Systems Cobas Sars-CoV-2 test Cobas 6800 and 8800 13%
*In early trade today. Note: excludes academic-developed tests. Source: FDA and company communications.

Abbott's Covid-19 test kit

Abbott Laboratories

Traditional and high-tech solutions needed in ventilator shortage

One thing is certain from the ongoing Covid-19 pandemic: hospitals and healthcare systems need more respirators. While some governments have called on non-medtech manufacturers to turn their production lines to build ventilators this underestimates the complexity, as shown by data from EvaluateMedTech on the number of approvals of new ventilators by leading manufacturers in the past five years. While Resmed might lead the pack in terms of approvals, in the current climate it is manufacturing capacity that matters, an area where groups like Medtronic and GE Healthcare dominate. But ventilator manufacturers are claiming that increases in production could take three or four months, so solutions will not come soon. Some are hoping for results from open-source collaborations to use 3D printing to create ventilators, and this approach has already resulted in the OSV group reportedly being ready to test its ventilator in Ireland as early as next week. However, rather than the complex machines such as Medtronic's Puritan Bennett 980 ventilator, OSV aims to automate the use of bag valve masks (Ambu-bags), a much simpler technology. While there is no disputing that this will be critical if estimated ICU numbers are correct, traditional ventilator manufacturers still need to step up.

Number of FDA ventilator approvals, 2014-2020
Resmed 7
Hamilton Medical 5
Hill-Rom 5
Philips 4
Medtronic 3
Thornhill Medical 3
Vyaire Medical 3
Getinge 3
General Electric 2
Flight Medical 2
Note: includes only continuous ventilators, which are likely to be used to treat Covid-19 patients. Source: EvaluateMedTech.

Two more test nods as FDA relaxes rules still further

Thanks to the FDA, Hologic and Labcorp have managed to arrest the damage they sustained during yesterday’s bloodbath on the exchanges: their shares are up very slightly after the agency granted emergency use authorisation to their Covid-19 diagnostics. The Hologic test could be particularly beneficial to US efforts to combat the virus if the company can make good on its intentions: it expects to provide tens of thousands of Covid-19 tests this month, rising to nearly 600,000 tests a month in April. That depends, however, on reagent supplies holding out. Meanwhile the FDA has taken a small step back from regulating Covid-19 tests, and will now allow individual states to authorise lab tests. Labs developing tests in these states would engage directly with state authorities, instead of with the FDA, and would not be required to pursue an emergency use authorisation. The FDA also said it would permit the sale of unapproved serological tests that detect antibodies to the coronavirus. Those tests are less complex, but also less accurate; the FDA’s guidance states that results from antibody testing should not be used as the sole basis to diagnose or exclude Covid-19 infection.

US FDA emergency use authorisations for Covid-19 tests 
Date of EUA Company Test  Instrument Turnaround time 1-day share price move
March 16 Labcorp Covid-19 RT-PCR test Applied Biosystems QuantStudio7 Flex 24hr 2%
March 16 Hologic Panther Fusion Sars-CoV-2 assay Panther Fusion 3hr 1%
March 13 Thermo Fisher Scientific TaqPath Covid-19 Combo Kit Applied Biosystems 7500 4hr 5%
March 13 Roche Molecular Systems Cobas Sars-CoV-2 test Cobas 6800 and 8800 3.5hr 13%
Note: excludes academic-developed tests. Source: FDA and company communications.

Regulatory pushback means DBV will struggle to stay in the peanut game

DBV Technologies has been struggling to get its peanut allergy patch Viaskin Peanut across the finish line for well over a year, and its latest trip-up could prove fatal. The FDA has now asked for more data about the project’s effectiveness, specifically over whether the patch could lose potency if not stuck properly to the skin. DBV says it has that data – and can show that adhesion does not affect efficacy – but that gathering it all together could mean big delays. The project still has an August PDUFA date, though a May advisory committee hearing has been cancelled. Fortunately for the company – less so for shareholders that bought in – DBV raised €136m ($147m) in February, meaning pro forma 2020 year-end cash was €308m, which should easily stretch until next year. However, the 57% plunge in DBV stock suggests that investors will not be dipping in their pockets again. Aimmune has recently launched its rival peanut allergy offering, Palforzia, but big question remain around the commercial potential of these products. Perhaps if Palforzia is a runaway success DBV will be revived. But, in the current market, few will be willing to play the long game here.

Astra reveals CTLA-4 inhibition’s deleterious effect

There was already ample evidence that Astrazeneca’s anti-CTLA-4 MAb tremelimumab was pharmacologically inert, but full data from the Caspian study could show it to be even worse. The trial, in first-line SCLC, was a success for its Imfinzi plus chemo cohort, which extended overall survival versus chemo, but a third arm, adding tremelimumab on top of Imfinzi and chemo, had been kept under wraps. Until today, that is, when Astra revealed that not only had this failed to beat Imfinzi, it failed to extend overall survival versus chemo alone. Of course, this does not necessarily mean that adding tremelimumab causes patients to die more quickly, and one explanation is that its side effects are causing patient drop-outs, leading to a loss of statistical power and failure to show significance. But it does bode ill for the few remaining pivotal tremelimumab-containing studies that have yet to read out; so far the Poseidon trial marks the key positive result, though even here tremelimumab’s role is unclear. Full numerical data from Caspian’s combo cohort should make fascinating reading when they are presented at a scientific meeting, though given the Covid-19 pandemic when this will happen is anyone’s guess.

Selected pivotal studies containing tremelimumab
Trial Cancer type Treatment cohort(s) Enrolment Result/primary completion
Arctic 3rd-line NSCLC Imfinzi +/- tremelimumab 597 Fail
Eagle 2nd-line head & neck Imfinzi +/- tremelimumab 736 Fail
Mystic 1st-line NSCLC Imfinzi +/- tremelimumab 1,118 Fail
Poseidon 1st-line NSCLC Imfinzi + chemo +/- tremelimumab 1,000 Both cohorts positive for PFS, but no inter-cohort comparison given
Neptune TMB-high, 1st-line NSCLC Imfinzi + tremelimumab 953 Fail
Danube 1st-line urothelial Imfinzi +/- tremelimumab 1,126 Fail
Caspian 1st-line SCLC Imfinzi + chemo +/- tremelimumab 988 Imfinzi arm positive for OS, tremelimumab combo arm negative 
Kestrel 1st-line head & neck Imfinzi +/- tremelimumab 823 Jan 2020
Himalaya 1st-line hepatocellular Imfinzi + tremelimumab 1,310 Mar 2020
Strong Various Imfinzi +/- tremelimumab 869 Apr 2021
Nile 1st-line urothelial Imfinzi + chemo +/- tremelimumab 885 Apr 2022
Adriatic SCLC maintenance Imfinzi +/- tremelimumab 600 Feb 2024
Source: & EvaluatePharma.
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