TG pulls victory from the jaws of defeat

The Unity-CLL trial shows ublituximab plus umbralisib conferring an unexpected progression-free survival benefit.

With TG Therapeutics yesterday claiming victory in the Unity-CLL trial, the study’s standing among biotech’s most curious is confirmed. Unity-CLL had suffered numerous delays and had its focus changed after an initial failure, but despite all this it has apparently shown a strong progression-free survival benefit.
The result positions the combo TG tested, ublituximab plus umbralisib, to be filed by the end of 2020 for chronic lymphocytic leukaemia (CLL). The projects’ sales will depend on the absolute benefit seen, the safety profile, and how strong the Unity-CLL result was in first-line versus relapsed/refractory subjects.
Investors seeking answers to these questions will need to wait until the full data are presented at a medical meeting – Ash in December looks a likely venue. Sellside consensus compiled by EvaluatePharma sees the two projects generating a combined $1.7bn of revenue in 2026, though this includes some $300m from ublituximab’s separate potential use in multiple sclerosis.
High statistical significance
For now, however, TG can boast of a PFS benefit for its combo that beat the comparator cohort, Roche’s Gazyva plus chlorambucil, with a high degree of statistical significance (p<0.0001).
Though the still undisclosed absolute result is key, TG closed up 34% yesterday, with a valuation of $1.8bn, and today took the opportunity to tap the market for $60m. TG separately hopes to complete a US lymphoma filing for umbralisib monotherapy by mid-2020.
For Unity-CLL, however, the biggest mystery remains why a study that had failed to show a benefit in terms of objective response would nevertheless read out positively for PFS. If patients are progression-free it is logical to expect them to be responding, but the TG readout suggests no correlation between the two measures.
Alethia Young, an analyst at Cantor Fitzgerald, said Unity-CLL had been powered to show a 40% improvement in PFS, and the goal was for the combo to reduce risk of progression by 29% (HR=0.71). Given that this was an interim result, causing Unity-CLL to be halted early for efficacy, the actual HR should be even better, “in the neighbourhood of 0.50”, wrote Ms Young yesterday.
A separate question is how ublituximab, an anti-CD20 antibody, and umbralisib, a PI3K delta inhibitor, will compete against new regimens such as Abbvie/Johnson & Johnson’s Imbruvica and Roche/Abbvie’s Venclexta. In first-line CLL Venclexta plus Gazyva cut risk of progression versus Gazyva plus chlorambucil by 67%, while Imbruvica beat chlorambucil alone with a staggering HR=0.16.
Importantly, Unity-CLL comprised first-line as well as relapsed/refractory subjects, in a ratio of 60/40. Though TG insists that the PFS benefit was observed across both populations, the precise contribution of each will be a key datapoint to watch, and should determine the drugs’ potential labels.
PI3K first
On an analyst call yesterday TG hailed its combo as being the first to show the benefit of a PI3K delta inhibitor in front-line CLL; this mechanism, courtesy of Gilead’s ill-fated Zydelig, has become associated with toxicity, and assuming that TG’s safety data hold up this could be a key selling point.
TG also said Unity-CLL was a springboard for additional combinations, and the company’s pipeline also includes a BTK inhibitor, TG-1701.
Still, investors would be right to remain cautious until the full data are disclosed. Unity-CLL’s failure to show a remission rate benefit scuppered TG’s accelerated approval plan, and prompted a change of focus to PFS. Then the PFS readout was delayed twice, forcing the company to add an interim analysis (TG shrugs off another delay, but history is against it, March 4, 2020).
It is with this analysis that TG has, at the eleventh hour, found something positive. Whether it has struck gold will only become clear once the full data are known.
https://www.evaluate.com/vantage/articles/news/trial-results/tg-pulls-victory-jaws-defeat

Novo’s Nash play takes shape

As semaglutide looks set to move into pivotal trials in Nash, Novo Nordisk lays out hopes for longer-term benefits.

Encouraging mid-stage results from semaglutide in Nash were a big focus at Novo Nordisk’s quarterly results today, and the diabetes giant looks to be gearing up for a push into phase III.
This is despite the GLP-1 agonist failing to hit the key secondary endpoint of the study, looking at fibrosis resolution; Novo seems to believe that semaglutide could improve this liver scarring over longer periods. Still, a convincing hit on the primary Nash resolution endpoint sets the drug up as a formidable competitor to other projects nearing crucial readouts, Genfit’s elafibranor in particular.
Elafibranor’s phase III Resolve-It trial, due to report in the coming weeks, is expected to use the proportion of patients achieving Nash resolution without worsening of fibrosis at 72 weeks for its primary endpoint – the same as the Novo study that was detailed today. Semaglutide hit statistical significance at all doses tested: a 42% placebo-adjusted difference in the high group provides something of a bar to beat.
Novo’s study tested once-daily injections of sema at three different doses; the drug is sold in diabetes as a once-weekly injection, branded Ozempic, and formulated for once-daily oral dosing and sold under the trade name Rybelsus.

Novo Nordisk Q1 2020 presentation.

Missing the key secondary endpoint – at least one stage of liver fibrosis improvement with no worsening of Nash – is disappointing, but then this was always a long shot given sema’s mechanism. The drug works mainly through metabolic and endocrine pathways, and in diabetes has been proven to promote weight loss.
This was also seen in the Nash trial, it was revealed on an analyst call this afternoon. Mads Krogsgaard Thomsen, Novo’s chief scientific officer, said “trends were positive” on the fibrosis improvement secondary endpoint, despite missing statistical significance.
Fibrosis progression endpoints did show a statistically significant and dose-dependent reduction, he added, suggesting that sema’s impact on liver scarring could be seen in longer trials.
These data “point towards a disease mechanism that has the potential to arrest progression of the disease, including fibrosis”, he said. Novo envisions gaining approval based on the Nash resolution with no worsening in fibrosis endpoint, and then continuing the study to collect a longer-term picture of the drug’s utility.
“There are good reason to believe that achievements in hard outcomes over time should be doable,” Mr Thomsen said.
Novo also seems confident that gastrointestinal tolerability issues, a known side effect of the GLP-1 agonist class, will not hold back development. Only 5% of patients in the study discontinued because of adverse events, and only two out of 90 in the high-dose group specifically for GI issues.
Moving on
Novo declined to discuss when pivotal studies might start, and with new trial starts paused because of Covid-19 this is understandable. A once-weekly dose is likely to be used, Mr Thomsen said, stressing that he was not awaiting impending results from a study testing sema in combination with two Gilead Nash projects before deciding whether to push on.
“Semaglutide looks to become a standalone and maybe an anchor drug in the future for Nash,” he said.
Such sentiments have been heard from several small Nash players in the past few years, of course, and most have come to nothing. But the diabetes giant is not known for its hyperbole, and has already set out lofty ambitions in the related obesity space.
Novo might not be the most advanced Nash player right now, but its deep experience in metabolic disease, and equally deep pockets, make it very well placed to succeed. Its next step will be keenly awaited.

https://www.evaluate.com/vantage/articles/news/trial-results/novos-nash-play-takes-shape

FDA clamps down on Covid-19 antibody tests

Tests from Ortho-Clinical Diagnostics and Becton Dickinson are in the danger zone as FDA moves to pull less accurate Covid-19 kits.

So far the US FDA has granted emergency use authorisation to 10 commercially developed blood tests that are intended to assess whether a person has developed antibodies to the novel coronavirus, and therefore might carry some level of immunity. But the evidence backing these disparate assays varies in quality, and some other groups are selling tests in the US, quite legally, without providing any accuracy data at all.
The FDA is finally doing something about this situation. On Monday it said developers would have to provide accuracy data within the next 10 days or risk their tests being pulled. Furthermore, the regulator has set out the exact standards it will require the tests to meet – and some of those on the market will not, on current evidence, make the cut.
The agency has previously not required accuracy data on a test to award an EUA – and companies do not have to obtain an EUA to sell their tests in the US anyway. Abbott, for example, obtained EUA for its antibody test on April 26, but had started selling it in the US on April 15. It is not known exactly how many antibody tests are on sale in the country, but the figure is believed to be in the hundreds.
This soft-touch approach is to change. Stating that “the careful balancing of risks and benefits has shifted from where it was in mid-March”, the agency has revised its policy and laid out the kind of evidence it needs to allow Covid-19 antibody tests to remain on sale.
Instead of sensitivity and specificity the FDA has used the terms positive and negative percent agreement (PPA and NPA). These values are calculated identically to sensitivity and specificity, but are used when the comparator test is recognised as being imperfect. In this case the best available comparator is PCR testing for coronavirus RNA, which is not currently recognised as a clinical reference standard.
Meeting the standards
In summary, the FDA states that the data backing Covid-19 antibody tests should demonstrate a minimum overall 90% PPA, equivalent to sensitivity, and overall 95% NPA, equivalent to specificity. For tests that report specifically IgM and IgG results, minimum PPAs of 70% and 90% are required for IgM and IgG respectively.
The guidance also states that clinical agreement data should be provided using at least 30 antibody-positive samples for each immunoglobulin claimed, and 75 antibody-negative samples.
The table below summarises the accuracy figures made for some of the tests known to be on sale in the US. An important caveat is that it relies on information the companies, and in some cases distributors or academic researchers, have released. The companies might well have better data that they have kept confidential – though why they would do this is unclear.

Accuracy figures for selected Covid-19 antibody tests sold in the US
Company	Test name	Date of US EUA	Sensitivity or PPA (%)	Specificity or NPA (%)	Meets FDA requirements?
Cellex	qSars-CoV-2 IgG/IgM cassette rapid test	Apr 1	93.8	95.6	Yes
Ortho-Clinical Diagnostics	Vitros anti-Sars-CoV-2 total reagent pack	Apr 14	83.3	100.0	No
Chembio Diagnostic System	DPP Covid-19 IgM/IgG system	Apr 14	93.5	90.2	No
Diasorin	Liaison Sars-CoV-2 S1/S2 IgG test	Apr 24	97.4	98.5	Yes
Ortho-Clinical Diagnostics	Vitros anti-Sars-CoV-2 IgG reagent pack	Apr 24	87.5	100.0	No
Autobio Diagnostics*	Anti-Sars-CoV-2 rapid test (IgM and IgG)	Apr 24	93.0	100.0	Yes
Abbott Laboratories	Abbott Sars-CoV-2 IgG test	Apr 26	100.0	99.5	Yes
Bio-Rad Laboratories	Platelia Sars-CoV-2 total Ab assay	Apr 29	98.0	99.0	Yes
Roche	Elecsys anti-Sars-CoV-2 antibody test	May 2	100.0	99.8	Yes
Euroimmun (Perkinelmer)*	Anti-Sars-CoV-2 Elisa (IgG)	May 4	65.0	96.0	No
Becton Dickinson/ Biomedomics	Covid-19 IgM/IgG rapid test	No EUA	88.7	90.6	No
Creative Diagnostics	Sars-CoV-2 antibody Elisa	No EUA	94.5	100.0	Yes
CTK Biotech	OnSite Covid-19 IgG/IgM Rapid Test	No EUA	96.9	99.4	Unknown
Epitope Diagnostics	EDI Novel Coronavirus Covid-19 IgG Elisa kit	No EUA	100.0	100.0	No
Epitope Diagnostics	EDI Novel Coronavirus Covid-19 IgM Elisa kit	No EUA	45.0	100.0	No
Intec Products	Rapid Sars-CoV-2 antibody (IgM/IgG)	No EUA	95.2	98.0	Unknown
Nirmidas Biotech	Covid-19 (Sars-CoV-2) IgM/IgG antibody detection kit	No EUA	81.4	94.4	No
SD Biosensor	Standard Q Covid-19 IgM/IgG Duo	No EUA	81.8	96.6	No
*Accuracy figures from this paper. All other accuracy claims made by companies or distributors. Includes only tests with FDA emergency use authorisation. Source: EvaluateMedTech & company websites.

Some of the tests fail to meet the FDA’s standards for sensitivity/PPA or specificity/NPA. One example is the test developed by Biomedomics, which is sold by Becton Dickinson. Others fail on the sample size on which the testing was conducted – Epitope Diagnostics’ IgG test was validated on too few samples, and CTK Biotech, for instance, claims sufficient accuracy for its test but has not provided the sample sizes.
There is also a separate plan for the FDA, in conjunction with the CDC and NIH, to double-check the accuracy of tests on sale in the US. This collaboration has looked at 13 tests so far, the FDA said, with the data still under review. The agency recently issued an umbrella EUA for antibody tests that complete this validation process, and will announce in future which tests have made the grade.
The question is whether the FDA will follow up on its promise to remove underperforming tests from sale in the US. If this is left as an idle threat, the agency risks being seen as toothless.
https://www.evaluate.com/vantage/articles/analysis/spotlight/fda-clamps-down-covid-19-antibody-tests

Fever scanners coming to GM factories

General Motors (NYSE:GM) will deploy a total of 377 FLIR (NASDAQ:FLIR) scanners across 72 sites to detect workers for high temperatures before employees return to factories on May 18.

Until the coronavirus pandemic, the bulk of thermal camera sales were for military or industrial purposes, but sales are now booming.

FLIR CEO James Cannon said on an earnings call yesterday that the company saw about $100M in bookings for coronavirus-related cameras and sensors during Q1.

https://seekingalpha.com/news/3570865-fever-scanners-coming-to-gm-factories

Sabra Health Care Q1 FFO beats consensus; no rent disruption yet

Sabra Health Care REIT (NASDAQ:SBRA) Q1 normalized FFO per share of 45 cents beats the 44-cent Visible Alpha consensus.

To date, the REIT hasn’t seen a material disruption from the COVID-19 pandemic in the monthly payment of rents and hasn’t utilized any deposits or other credit enhancements for payment of rent as a result of the COVID-19 pandemic.

As of April 30, SBRA hasn’t granted any rent deferrals or other rent relief related to the COVID-19 pandemic.

Its operators have received or expect to receive an aggregate of ~$320M in assistance under various provisions of the CARES Act and other state and federal assistance programs.

Based on data received from its operators, through the last week of April, Senior Housing – Managed occupancy declined 160 basis points from the February average.

Does not expect to make any material acquisitions or other investments in the near term, including the exercise of its option on the remaining 51% interest in the Enlivant joint venture.

Balance sheet has liquidity of $953.1M as of March 31, 2020 with no material debt maturities until 2024.

Conference call on May 7 at 1:00 PM ET.

Previously: Sabra Health Care EPS misses by $0.04, misses on revenue (May 6)

https://seekingalpha.com/news/3570790-sabra-health-care-q1-ffo-beats-consensus-no-rent-disruption-yet

CVS Health Warns of Surge in Non-Coronavirus Health Problems

CVS Health Corp. executives warned Wednesday of an impending surge in medical problems unrelated to coronavirus, as the pharmacy chain’s data suggest Americans are delaying routine health care during the pandemic.
CVS, which owns insurance giant Aetna, says patients in April received fewer new prescriptions, starting fewer new treatments and seeing doctors less frequently, a concern especially for patients who have chronic conditions such as diabetes and heart disease, which can lead to costly hospitalizations when not treated consistently.
Meantime, store and prescription sales dropped in April following a pandemic-driven surge in business earlier in the year, the company said. Aetna also saw a decline in commercial contracts as businesses dropped insurance coverage for workers to cut costs, laid off workers or closed.
The emerging trends follow a first quarter during which CVS had higher sales as the pandemic prompted consumers to fill more routine prescriptions and to spend more at the pharmacy chain’s stores.
The pandemic has led to dramatic shift in consumer patterns, the company said. Virtual visits to the company’s urgent-care clinic grew sixfold while prescription home delivery grew 10-fold. Online prescription refill requests grew 50%.
“We are seeing a new normal emerge,” CVS CEO Larry Merlo said. “We expect elements of today’s new norm will become part of tomorrow’s everyday routines.”
CVS’s Aetna unit saw a drop-off of around 30% in use of health-care services in April, as much of the health-care system paused elective procedures to brace for coronavirus surges.
But Mr. Merlo said in an interview that the Aetna business has picked up slightly in response to shelter-in-place orders being lifted in certain locations. The company expects “the trough, the low point will be in the second quarter, and we will see some pickup in the second half of the year,” but it is too soon to tell how soon or how much, Mr. Merlo said.
While people weren’t starting new drug therapies for health conditions, Mr. Merlo said it appeared that patients with chronic conditions were keeping up their existing prescriptions.
Prescription volume for the quarter ended March 31 grew more than 8%, as customers rushed to stock up on medications amid the pandemic, either by refilling prescriptions early or switching to 90-day prescriptions. Same-store sales grew 8% and shoppers scooped up health-related items and other goods.
“We’re uniquely positioned to understand consumer and patient needs and how to address them,” Mr. Merlo said in a statement.
CVS reported first-quarter net income of $2 billion, or $1.53 a share, compared with $1.4 billion, or $1.09 a share, in the comparable quarter a year before. Adjusted earnings were $1.91 a share.
Analysts were looking for earnings of $1.22 a share, or $1.62 a share on an adjusted basis.
CVS said its revenue rose 8.3% to $66.8 billion from the same period the year before as revenue grew across all segments. Analysts were targeting $64.1 billion.
Revenue in its retail segment, which fulfills prescription medications and sells a range of merchandise, was $22.7 billion, up 7.7% compared with the year-earlier period. CVS has faced pressure in its retail-pharmacy business but has begun to fare better than rival Walgreens Boots Alliance Inc.
Walgreens also generated stronger-than-expected sales during its latest quarter, though the company’s operating income fell 19%, in part because of reimbursement pressure on prescription drugs. Like CVS, Walgreens said sales in April dropped off following a surge in March.
CVS’s health-care benefits business, which includes Aetna, posted revenue of $19.2 billion, an increase of 7.4%. The company last year sold its Medicare Part D prescription business to a WellCare Health Plans Inc., but said it generated more revenue in the quarter from government products.
Revenue grew 4.2%, to $35 billion, in the pharmacy-services segment.
CVS said its expectations for full-year earnings and cash flow remain unchanged while withdrawing guidance for all other metrics due to uncertainty around coronavirus.
CVS shares were up nearly 1% in afternoon trading.

https://www.marketscreener.com/CVS-HEALTH-CORPORATION-12230/news/CVS-Health-Warns-of-Surge-in-Non-Coronavirus-Health-Problems-2nd-Update-30551539/

China’s BGI gets Australian foothold through mass coronavirus test delivery

Australia says its purchase of 10 million coronavirus test kits from Chinese genomics company BGI will not risk patient privacy, as researchers hope for greater price competition in a biotech market dominated by a U.S rival.
The deal was struck even as relations between Australia and China have been strained by Australia’s call for a global enquiry into the coronavirus outbreak, which China has framed as a U.S.-led attempt to blame it for the pandemic.
BGI – Beijing Genomics Institute – has grown into one of the world’s largest genomics companies in the two decades since it worked on the Human Genome Project. It has one lab in Australia and had been seeking to expand its genome sequencing services.
BGI, whose BGI Genomics Co is listed on the Shenzhen stock exchange, was named as having “evident links” to the Chinese government in a U.S. Trade Office report into Chinese technology transfer practices that was used to justify the U.S. imposition of tariffs on Chinese exports.
There are also concerns about its work in China, including providing gene technology used for surveillance of the Uighur ethnic minority in China’s western Xinjiang region.
BGI is also defending multiple patent lawsuits from U.S. firm Illumina Inc, the dominant player in the Australian market.
But unlike the Australian government’s move to effectively exclude Chinese telecom giant Huawei from its 5G network on national security grounds because of its perceived links to Beijing, security agencies have approved the mass use of BGI technology to combat the novel coronavirus.
Australian pathology companies have installed BGI’s nucleic acid extraction machines in 11 laboratories, to process the tests automatically, BGI said in a statement.
A spokesman for Australian health minister Greg Hunt said privacy laws covered pathology tests and patient data, and the use of BGI equipment had been approved by security agencies.
“BGI will have no access to patient information as they will not be operating the labs,” the spokesman said in a statement, with pathology companies required to comply with security agency advice on installing BGI’s technology.
“The extent of BGI’s involvement with existing Australian laboratories will be limited to the installation of COVID-19 pathology testing platforms and training of staff.”
‘COMPLEX COMPANY’
Asked about privacy concerns, BGI Australia Director Bicheng Yang said Australian pathology labs would operate under national guidelines.
“BGI provided technology transfer and the equipment does not collect personal data. The process tests the viral RNA (ribonucleic acid) only, if it is present,” Yang said in a statement to Reuters.
The technology used to test for the coronavirus is different from those used in the diagnosis of other rare diseases, cancer and birth defects in pregnancy, but the scale of the coronavirus programme will boost BGI’s links with Australian laboratories, Australian researchers who work with BGI said.
Marcel Dinger, president of the Australian Genomics Technologies Association and a director of Pryzm Health, a data science company that develops rare disease diagnosis software, said most gene sequencing in Australia was supplied by Illumina.
“They have the lion’s share by a long way in the market when it comes to genome sequencing. BGI have a fairly equivalent technology now … They are really a competitor in the market with real potential to disrupt,” he said.
BGI wants to bring the cost of sequencing a patient’s whole genome down to a few hundred dollars, Dinger said.
“It would make genome sequencing more widely available”.
BGI owns the China National Genebank, containing 11 million human, plant and animal DNA samples.
Australia does not have a national genome database because privacy concerns have stopped its development, Dinger said.
La Trobe University associate professor James Leibold said there were “larger ethical issues” associated with BGI, including data privacy, its use of the world’s largest gene database, and providing gene technology for surveillance of the Uighurs in Xinjiang.
“They are a complex company that operates under a different ethical framework,” Leibold, who is an expert in Uighur studies and is critical of the Australian health agency’s decision to work with BGI, told Reuters.
https://www.marketscreener.com/ILLUMINA-INC-9659/news/Illumina-China-s-BGI-gets-Australian-foothold-through-mass-coronavirus-test-delivery-30547306/