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Saturday, October 5, 2019

Study suggests inaccuracies in physicians’ electronic documentation

  • A new study in JAMA Network Open found inconsistencies between the way emergency department residents documented patient encounters in an EHR and what trained observers witnessed.
  • In the study, 12 observers (including two physicians and 10 undergraduate students with an interest in medicine) shadowed nine physicians during 180 patient encounters in the emergency departments of two teaching hospitals, which weren’t identified. They focused their observations on two parts of each encounter: the review of systems, where physicians ask patients about their symptoms, and the physical exam. The encounters were recorded.
  • Residents documented a median of 14 systems (or organs in the body) as being discussed with patients during the review of systems portion of the encounter, while observers recorded a median of five systems, the ​study found. During the physical exams, physicians documented a median of eight systems examined per encounter, while observers noted a median of 5.5.
CMS has developed complicated rules and regulations about how to document a patient encounter to account for the severity and complexity of a patient case and the amount of time a physician spends working on it. But recognizing that the documentation rules may be burdensome and outdated, officials have said they are working on reforming the process.
Heavy documentation and charting workloads are a cause of provider burnout, which is a major concern to health systems, hospitals and medical groups because burnout can lead to worsening well-being for physicians and lower-quality patient care.
It’s also costly for the healthcare industry. For example, a recent study published in the Annals of Internal Medicine calculated annual burnout costs between $2.6 billion and $6.3 billion, including costs from staff turnover, lower productivity and other factors.
Burnout is not the only consequence of complicated documentation requirements.
The study’s authors note that CMS rules create unintended incentives for providers to maximize reimbursement from payers by documenting extensively.
This problem is compounded by a feature in some EHRs that allows providers to auto-populate required fields in the software when documenting, particularly for the review of systems and physical exam portions of a patient encounter, the study authors wrote. However, auto-populating can lead to inaccuracies if the data entered into the fields does not reflect the specific circumstances of a patient case.
Inaccurate documentation also increases the risk of patient safety issues, which can impact patient outcomes, providers’ quality scores, reputation and revenues under value-based reimbursement models. Faulty documentation also exposes facilities to the risk of payer audits.
In an accompanying editorial, commentators from the Icahn School of Medicine at Mount Sinai note that studies analyzing the accuracy of electronic documentation are rare but necessary. “An improved understanding of the root cause of discrepancies between patient report and physician documentation will be helpful in detecting ways to prevent them in the future,” they wrote.
https://www.healthcaredive.com/news/jama-study-suggests-inaccuracies-in-physicians-electronic-documentation/563154/

Sacklers reaped up to $13 billion from OxyContin maker, U.S. states say

OxyContin maker Purdue Pharma LP steered up to $13 billion in profits to the company’s controlling Sackler family, according to U.S. states opposing efforts to halt lawsuits alleging the company and its owners helped fuel the U.S. opioid epidemic.

The wealthy Sacklers received the money from Purdue during an unspecified time frame, according to court documents and portions of a deposition filed in the drugmaker’s bankruptcy proceedings this week.
Purdue ultimately transferred $12 billion or $13 billion to the family, a company adviser testified in the deposition. The deposition, taken last week, was revealed in court filings on Thursday and Friday.
The financial figure is significantly larger than the roughly $4 billion previous lawsuits have alleged the Sacklers took out of Purdue, and was cited as part of coordinated legal broadsides this week against the company’s attempts to shield itself and the family from sprawling opioid litigation.
Many states want the Sacklers to contribute more than an initial $3 billion they have pledged toward resolving the lawsuits as part of a settlement Purdue has proposed.
Attorneys general from 24 states and the District of Columbia on Friday objected to Purdue’s September request that a U.S. bankruptcy judge halt more than 2,600 lawsuits seeking billions of dollars in damages, and they raised financial transfers to the Sacklers in their legal arguments.
So, too, did lawyers representing 500 cities, counties and Native American tribes, according to an earlier court filing.
“The distribution numbers do not reflect the fact that many billions of dollars from that amount were paid in taxes and reinvested in businesses that will be sold as part of the proposed settlement,” said Daniel S. Connolly, a lawyer for family members facing lawsuits who are related to the late Raymond Sackler, one of the modern Purdue’s co-founders, in a statement.
A spokesman for relatives of another deceased company co-founder, Mortimer Sackler, who also face litigation, had no immediate comment.
Purdue had no immediate comment on the payments. The company and family have denied allegations they contributed to the U.S. opioid crisis.
The lawsuits, largely brought by state and local governments, allege Purdue and the Sacklers contributed to a public health crisis that has claimed the lives of nearly 400,000 people since 1999 by aggressively marketing opioids while downplaying their addiction and overdose risks.
“The Sacklers are billionaires, they are not bankrupt,” Massachusetts Attorney General Maura Healey, among the officials opposing Purdue’s efforts to halt lawsuits, told Reuters in an interview. “They should not be allowed to use the filing to shield their assets.”
Purdue filed for Chapter 11 bankruptcy protection last month after reaching a deal it valued at more than $10 billion that would resolve the bulk of the cases against the company and the Sacklers.
The company contends it needs the litigation against it and the Sacklers paused for about nine months so it can attempt to settle with hold-out plaintiffs and preserve money that would otherwise be spent fighting the cases.
Purdue said the costs of continued litigation were “staggering,” putting its legal expenses this year at nearly $250 million.
“Without a stay of the litigation, only lawyers will win,” the company said in a statement.
Typically, a bankruptcy filing triggers an “automatic stay” of all litigation without a specific order from a judge.
However, Purdue is seeking an injunction to stop the lawsuits because the Sacklers did not seek bankruptcy protection and there is an exception to the automatic stay for government actions that seek to enforce laws related to public health and safety.
Healey said the exception gives the states a strong argument to move forward with their cases against the OxyContin maker. “We’re exercising our police power and have the right to do so,” she said.
The Sacklers have offered to cede control of Purdue to the plaintiffs and contribute $3 billion, and potentially more through the sale of another pharmaceutical business they own, toward the proposed settlement. Purdue is also in discussions to resolve a U.S. Justice Department probe that could carry a financial penalty.
Healey said the Sacklers should increase their contribution and she criticized the structure of the deal, which is premised in part on the continued sale of OxyContin, a drug that critics say helped launch the nation’s opioid addiction crisis.

https://www.marketscreener.com/news/Sacklers-reaped-up-to-13-billion-from-OxyContin-maker-U-S-states-say–29336762/

Social Security Debate Shifts From Benefit Cuts to Bigger Checks

The Social Security debate has moved left.
That shift, evidenced by presidential candidates’ plans and a bill backed by nearly 90% of House Democrats, departs from years of conversations about an elusive bipartisan compromise where Democrats agree to lower promised benefits and Republicans accept higher taxes.
Instead, President Trump has ruled out cuts to future benefits. Democrats have lined up behind larger benefits and higher taxes.
Democrats’ proposals show a party growing more comfortable with tax increases and shifting away from trying to reduce budget deficits. They have been nudged by activists trying to reset Social Security discussions dormant in Congress since the failure of President George W. Bush’s partial privatization plan.
Now, Democrats want to expand the popular program, emphasizing low-income retirees, widows and people who left the workforce to care for family members.
“Whatever we do is going to be bold,” said Rep. Dan Kildee (D., Mich.).
President Trump’s no-benefit-cuts position in 2016 shrank the partisan divide, tempering the Democrats’ advantage on the issue. Positions taken since then by House Democrats and candidates Elizabeth Warren, Bernie Sanders and Joe Biden widen that gap again.
“It’s an interesting story of how a policy position, whether I agree with it or not, can go from being a fringe position to a dominant position of a political party in a relatively short period of time,” said Andrew Biggs, resident scholar at the conservative American Enterprise Institute.
Unlike other safety-net programs such as food stamps, Social Security is viewed as an earned benefit, because it is largely funded through payroll taxes and check sizes are calculated based on earnings. It enjoys unique support across age groups and political affiliations.
In a 2018 Pew Research Center poll, 78% of Democrats and 68% of Republicans opposed cuts in future benefits. Younger voters showed more support for reducing future benefits, and 42% of people ages 18 to 29 assume they won’t get any benefits.
Social Security presents a political challenge, but it is also a math problem. Today’s taxes must generate enough money to pay benefits that today’s recipients accrued over their working lives. That math is changing. The demographic bulge of baby boomers is retiring, and living longer. Because high-income workers have experienced faster wage growth than the rest of the population, a greater share of U.S. wages is now exempt from the payroll tax, which stops at $132,900. That smaller tax base contributes to the long-run shortfalls.
Costs are projected to exceed income next year for the first time since 1982, forcing the program to dip into its nearly $3 trillion trust fund, built up when payroll taxes exceeded benefits.
Unless Congress acts, that trust fund will be depleted in 2034 and benefits would be automatically cut by more than 20%. Congress could fill the gap by raising payroll taxes or diverting general-fund revenue. Less disruptive changes now could close the shortfall, but lawmakers have little incentive to move.
Make benefits richer, and the trust fund runs out sooner. Raise taxes, increase the retirement age or slow benefit increases, and the program stays solvent longer.
Ms. Warren would increase everyone’s benefits by $200 a month, paid for in part by taxing investment income. Mr. Biden would give a bonus to the oldest Americans, and raise payments to surviving spouses. Mr. Sanders would tax wages above $250,000 to extend the program’s solvency and raise minimum benefits.
That is all far from where Democrats were earlier this decade, when both parties focused on deficit reduction. As part of a deal, President Obama proposed a formula under which Social Security benefits would grow more slowly.
By late 2016, however, Mr. Obama embraced more generous benefits, and presidential candidate Hillary Clinton backed expansion. Mainstream Democrats joined progressives like former Sen. Tom Harkin of Iowa in support of boosting benefits.
“Now, we’re seeing some variations on a theme,” said Nancy Altman, president of Social Security Works, an advocacy group. “It becomes a clear distinction between the parties.”
A plan from Rep. John Larson (D., Conn.) would expand benefits, raise payroll taxes and lower income taxes on benefits.
Mr. Larson’s Social Security 2100 Act would gradually bump the tax rate from 6.2% each on employers and employees to 7.4% each by 2043. That would hit every worker, including low-income ones. Social Security’s progressive benefit structure counteracts that regressive tax.
Mr. Larson would also impose payroll taxes on wages above $400,000, leaving an exemption for wages between $132,900 and $400,000. Eventually, inflation would erase that gap and all wages would face Social Security taxes.
His plan would extend Social Security’s solvency for at least 75 years, according to the chief actuary of the Social Security Administration. But the Congressional Budget Office, using different methodology, says solvency would last only through 2041.
Mr. Larson wants a House vote soon, though his bill stands little chance of becoming law with Republicans running the White House and Senate. He said the way the 2008 financial crisis sapped private retirement savings underscored the importance of Social Security’s guarantee and helped drive Democrats toward benefit expansion. Nearly 90% of House Democrats, 209, have signed on to the bill.
“This is a bipartisan issue across the country,” he said. “Not a bipartisan issue in Congress. But I think once people have to vote on it, it might become more bipartisan than people imagined.”
Republicans call the Democratic proposals nonstarters, but they haven’t coalesced around anything.
Some GOP lawmakers say they are open to a combination of revenue and spending changes and emphasize bipartisanship — as in 1983, when President Reagan and congressional Democrats raised the retirement age and accelerated scheduled tax increases.
Legislatively, that is likely required for any plan to become law. The fast-track, simple-majority procedure used for the 2017 tax cut and 2010 health law doesn’t apply to Social Security. One party would either need to get 60 votes or scrap the Senate filibuster.
“Democrats want to raise the payroll tax. Republicans aren’t wild about that, but it’ll be a compromise,” said Sen. Rob Portman (R., Ohio). “It has to happen soon to avoid the train wreck, so the sooner the better.”
But Mr. Trump vowed in 2016 to preserve promised Social Security benefits, helping himself politically but putting him at odds with many GOP lawmakers. Also, Republicans now rely more on older voters, making them more reluctant to reduce future benefits.
“It leads to them abandoning their prior policies on Social Security, but not knowing what their future policies are,” Mr. Biggs of the American Enterprise Institute said.
Nonpartisan groups still produce proposals along the old-compromise lines. Recently, the Concord Coalition and the Committee for a Responsible Federal Budget offered one designed to boost economic growth. It would encourage older workers to delay retirement and provide a “poverty protection benefit” for low-income workers.
But in Congress, there is little urgency or appetite for compromise proposals. Social Security may stumble toward insolvency in 2034 — sooner if there is a recession or later in a booming economy.
Rep. Tom Reed (R., N.Y.), the top Republican on the Social Security subcommittee, said some benefit increases might be worth examining. He opposes across-the-board increases or adding investment-income taxes.
“The longer we wait, we have fewer and fewer solutions that can be implemented in a practical way,” he said. “[I] would love to do this without tax increases or revenue increases, but it is clear if you do the math that is becoming more and more difficult.”
https://www.marketscreener.com/news/Social-Security-Debate-Shifts-From-Benefit-Cuts-to-Bigger-Checks–29340331/

Friday, October 4, 2019

Can Anti-TNF Meds for Inflammatory Diseases Reduce Alzheimer’s Risk?

Systemic inflammatory diseases involving tumor necrosis factor (TNF) increased the risk of Alzheimer’s disease, but that risk was reduced in patients who used anti-TNF biologics, an analysis of 56 million adults’ electronic health records showed.
While rheumatoid arthritis increased Alzheimer’s risk, it was reduced in patients taking etanercept (Enbrel), adalimumab (Humira), or infliximab (Remicade), according to Rong Xu, PhD, of Case Western University in Cleveland, and co-authors.
Similarly, people taking etanercept and adalimumab for psoriasis also had their risk of Alzheimer’s reduced, the researchers reported in a manuscript on the preprint server medRxiv.
These findings show the power of combining expert knowledge with big data analytics, Xu said. “Retrospective clinical studies using very large databases of patient electronic health records have high potential in uncovering risk associations among complex diseases and potential novel drug repurposing opportunities, as in this example where anti-TNF drugs might have a new use in Alzheimer’s disease and associated dementia,” she told MedPage Today.
The findings also reinforce the concept that late-onset Alzheimer’s may have multiple causes, added study author Mark Gurney, PhD, chief executive officer of Tetra Therapeutics in Grand Rapids, Michigan. “In this subset of patients, TNF produced in the body is an important risk factor for Alzheimer’s disease and is of the same magnitude as genetic risk factors such as APOE4,” Gurney told MedPage Today.
The analysis comes after years of speculation about how anti-inflammatory drugs might affect cognition. A phase II trial of etanercept in Alzheimer’s disease published in 2015 showed positive trends but no significant changes in cognition, behavior, or global function. Yet, observational data suggests there might be a link: a 2016 nested case-control study found that the relative risk of Alzheimer’s disease was lower in rheumatoid arthritis patients taking etanercept, and earlier this year, the Washington Post reported that Pfizer had insurance claims data showing that etanercept may lower Alzheimer’s risk by 64%.
The new research “adds further weight to the growing evidence that people who have diseases carrying a systemic inflammatory component have an increased risk of developing Alzheimer’s disease,” said Clive Holmes, MRCPsych, PhD, of the University of Southampton in England, who was not involved with the study.
“Furthermore, it clearly suggests that drugs that target peripheral inflammation — in particular, TNF inhibitors — have the potential to substantially reduce the risk of developing Alzheimer’s disease,” Holmes told MedPage Today. “Only a large randomized placebo-controlled clinical trial will definitively answer this question, but it is a question that clearly needs answering.”
This retrospective case-control study looked at electronic health records of 56 million unique adult patients from 360 hospitals and 317,000 providers, identifying patients with rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel disease, ulcerative colitis, or Crohn’s disease. Patients diagnosed with more than one inflammatory disease were excluded from the study.
The analysis compared a diagnosis of Alzheimer’s disease as an outcome measure in patients who received at least one prescription for a TNF-blocking agent (etanercept, adalimumab, and infliximab) or for methotrexate. A patient was considered “taking a medication” if at least one outpatient prescription for the medication had been written. Patients were included in the study if they were treated with a single TNF blocker but excluded if treated with two or more TNF-blocking drugs.
Alzheimer’s risk was increased in adults with the following diagnoses (all P <0.0001):
  • Rheumatoid arthritis: adjusted OR 2.06, 95% CI 2.02-2.10
  • Psoriasis: adjusted OR 1.37, 95% CI 1.31-1.42
  • Ankylosing spondylitis: adjusted OR 1.57, 95% CI 1.39-1.77
  • Inflammatory bowel disease: adjusted OR 2.46, 95% CI 2.33-2.59
  • Ulcerative colitis: adjusted OR 1.82, 95% CI 1.74-1.91
  • Crohn’s disease: adjusted OR 2.33, 95% CI 2.22-2.43
Rheumatoid arthritis patients treated with etanercept (adjusted OR 0.34, 95% CI 0.25-0.47), adalimumab (adjusted OR 0.28, 95% CI 0.19-0.39), or infliximab (adjusted OR 0.52; 95% CI 0.39-0.69) had a reduced risk of Alzheimer’s. Methotrexate also reduced Alzheimer’s disease risk, especially for patients who had a prescription history for both a TNF blocker and methotrexate.
Psoriasis patients treated with etanercept (adjusted OR 0.47; 95% CI 0.30-0.73) or adalimumab (adjusted OR 0.41, 95% CI 0.20-0.76) also had a reduced risk for Alzheimer’s disease.
Sex or race did not affect the results, but younger patients showed greater benefit from a TNF blocker than older patients, the researchers observed.
The study had several limitations, Xu and co-authors noted. Electronic health record quality or misdiagnoses may have affected outcomes. While the analysis suggests a potential therapeutic benefit of TNF-blocking agents in Alzheimer’s, it did not look at prevention or address how disease severity might influence results.
“The anti-TNF biologics are powerful drugs that can cause severe side effects,” Gurney said. “Further studies are necessary to understand their potential in treating or preventing Alzheimer’s disease in patients who do not have rheumatoid arthritis, psoriasis, or other inflammatory diseases as risk factors for Alzheimer’s disease.”
Last Updated October 04, 2019
Xu acknowledged support from the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under the NIH Director’s New Innovator Award, the NIH National Institute of Aging, and an American Cancer Society Research Scholar Grant. Gurney is an employee of Tetra Therapeutics and acknowledged support from the National Institute of Mental Health.
The researchers declared no competing interests.
Note that medRXiv is a preprint server for posting manuscripts prior to undergoing formal peer review. Data and conclusions should be regarded as preliminary until published in a peer-reviewed journal.

Upcoming events – Sage targets depression and Biogen aims for lupus

Sage’s big depression readout looms, while Biogen hopes for a mid-stage hit in lupus.

With a win in postpartum depression in the bag Sage Therapeutics’ attention with its oral GABA-A modulator SAGE-217 now turns to the big one: major depressive disorder (MDD). Data from the phase III Mountain trial are due in the fourth quarter, although this could slip into early next year.
The company needs a hit to help justify its $7bn valuation. It already sells the intravenous post-partum depression therapy Zulresso, but SAGE-217 is expected to be its biggest growth driver, with 2024 sales forecast to reach $1.8bn, according to EvaluatePharma sellside consensus. The oral project has a risk-adjusted NPV of $4.7bn.
Hopes are high going into the Mountain readout, but depression trials are notoriously tricky. The study tests two weeks’ SAGE-217 at 20mg or 30mg versus placebo, with four weeks’ follow-up. The primary endpoint is change from baseline in the 17-item Hamilton rating scale for depression (HAM-D) total score at 15 days; a higher score indicates more severe depression.
Sage bulls will point to the fact that the phase IIb trial of SAGE-217 in MDD met its primary endpoint, showing a seven-point improvement in HAM-D versus placebo at 15 days; in addition 64% of SAGE-217-treated patients achieved remission, compared with 23% of placebo recipients.
More recently, SAGE-217 prevailed in a phase III study in postpartum depression (JP Morgan 2019 – development shortcuts pay off for Sage, January 8, 2019). However, data from the single-arm Archway trial in bipolar depression disappointed, and Sage has chosen not to continue in this indication.
Safety will also be closely watched, as there have been reports of fainting with Zulresso, which has a similar chemical structure to SAGE-217. This would be particularly problematic for the oral drug, which would be given in an outpatient setting, whereas Zulresso is administered by a continuous intravenous infusion over 60 hours. Still, there have been no reports so far of fainting with SAGE-217.
Two further phase III trials of the oral project are looking at retreatment in MDD: Shoreline evaluates SAGE-217 on an as-needed basis, while Redwood will assess long-term dosing. Meanwhile the Rainforest study, in comorbid depression and insomnia, is also under way.
Climbing the Mountain: selected trials of SAGE-217
Study Details Trial ID Placebo adjusted change on HAM-D after treatment Share price reaction
Robin Phase III PPD NCT02978326 4 points, p=0.0029 43%
Phase IIb MDD NCT03000530 7 points, p=<0.0001 70%
Mountain Phase III MDD NCT03672175
MDD: major depressive disorder; PPD: postpartum depression. Source: Clinicaltrials.gov, company releases.
Homo homini lupus
Pipeline concerns have been laying Biogen low for some time now – the company’s R&D head of three years quit this week – so any signal of efficacy from BIIB059, a mid-stage lupus candidate, would give the beleaguered biotech a much-needed boost. Phase II results are due before the end of the year, and the trial looks rigorous enough to provide some fairly reliable pointers of activity.
BIIB059 binds BDCA2, a receptor found on plasmacytoid dendritic cells, immune cells that produce large amounts of type I interferon, a key driver of lupus. Plasmacytoid dendritic cells have been shown to accumulate in the skin, and it is hoped BIIB059 will have a particularly marked impact on the rashes seen in many lupus patients.
Data from a phase I study published earlier this year found significant reductions in interferon-related gene and protein expression in patients who received BIIB059, as well as improvements in skin-related disease activity.
The phase II, double-blind, placebo-controlled trial, Lilac, has enrolled distinct lupus populations into two separate cohorts, 264 in total.
Part A assesses a 450mg dose in subjects with systemic lupus erythematosus who suffer from lupus rash and painful joints. The primary measure is change on a joint pain assessment, incorporating 28 different joints, measured over 24 weeks.
Part B tests patients with various forms of lupus skin disease, including cutaneous lupus and discoid lupus, who may or may not have systemic disease. Three different doses are being used in this cohort – 50mg, 150mg and 450mg – and the primary endpoint is an activity score used in lupus skin diseases called CLASI-A. Change in baseline is measured over 16 weeks.
Lupus has proven a very difficult field for drug developers, so any positive signals from Lilac will need to be confirmed in a much larger study. Still, the recent surprise success with Astrazeneca’s anifrolumab suggests that progress is being made (Second time lucky for Astra in lupus, August 29, 2019).
Anifrolumab also targets INF-1, binding to receptors on the interferon; by turning off INF-1 at the source BIIB059 theoretically works earlier. Whether this makes any difference should soon begin to be answered.
https://www.evaluate.com/vantage/articles/events/upcoming-events/upcoming-events-sage-targets-depression-and-biogen-aims

Japanese drugmakers stand out at the nine-month mark

Daiichi Sankyo’s incredible stock market performance stands out amid the usual mixed bag of fallers and risers among biopharma’s mid- and small caps.

The third quarter of 2019 is unlikely to be a period remembered fondly by biotech investors. Not in the US anyway: the closely watched Nasdaq Biotechnology Index faded over the three months, eventually hitting a low for the year. Which means kudos must go to those US companies that have managed to remain in positive territory: Seattle Genetics and The Medicines Company stand out in Vantage’s quarterly look at biopharma share prices.
However it is Japanese groups that top both the mid- and small cap tables, with Daiichi Sankyo’s remarkable advance this year particularly notable. Its stock has almost doubled in value, pushing Daiichi’s market cap to $44bn, and well into the league of the sector’s bigger beasts. For example, the company is now worth considerably more than Regeneron and is on par with Biogen, two US biotechs that have been having a torrid time.
A licensing deal with Astrazeneca over Daiichi’s Her2 antibody-drug conjugate, DSD-8201, is largely behind the move; the project will be filed in the US later this year. Last month the Tokyo-based firm also won FDA approval for Turalio, a CSF1R-targeted kinase inhibitor, for a very rare cancer of the joints, and it is clear that investors have sat up and taken notice of the company’s progress.
Mid-cap ($5-25bn): top risers and fallers in first nine months of 2019

Share price  Market capitalisation ($bn)
Top 5 risers 9-mth change (local currency) 30 September 2019 9-mth change ($bn)
Daiichi Sankyo 94% 44.6 22.5
Galapagos 74% 9.7 4.7
Sino Biopharmaceutical 70% 16.1 7.8
Seattle Genetics 51% 13.8 4.7
Vifor Pharma 49% 10.5 3.5
Top 5 fallers


Teva Pharmaceutical (55%) 7.5 (9.3)
Sumitomo Dainippon (49%) 6.5 (5.8)
Nektar Therapeutics (45%) 3.2 (2.5)
Eisai (35%) 15.1 (7.3)
Piramal Enterprises (31%) 4.7 (1.2)
Another Japanese group, Sosei, tops the risers among the small caps, below. This is something of a recovery story – the company has suffered pipeline setbacks over the past couple of years, but recent progress with Novartis’s respiratory franchise, upon which Sosei will receive royalties, has provided a boost. A couple of big research collaborations with Takeda and Genentech also helped.
It is not all good news for Japanese drug makers, however. Sumitomo Dainippon remains one of the mid-cap laggards, and the company’s remarkable decision to hand over $3bn to Roivant for an eclectic mix of assets has not made up for a string of pipeline blow-ups and a looming patent cliff (Sumitomo bets on Roivant to solve its patent expiry woes, September 6, 2019).
Eisai, meanwhile, has been dragged down by disappointments in Alzheimer’s disease – the company was partnered with Biogen on the amyloid project aducanumab and the Bace inhibitor elenbecestat, both of which flunked phase III this year. The two companies are still working on another amyloid-targeting agent, BAN2401, but hopes are not high.
Europe is also well-represented among the mid-cap risers, with both Galapagos and Vifor notching up respectable gains. The former has benefitted from rising hopes for its Gilead-partnered Jak inhibitor, filgotinib, which could reach the market late next year and has been widely pegged as a future blockbuster. A huge research collaboration, forged between the two partners in July, also gave the Belgium company’s stock a boost.
Vifor Pharma, which sells products for iron deficiency and kidney disorders, has been a beat-and-raise story this year, with strong financial results driving share price gains. Hong Kong-based Sino Biopharmaceutical has also been delivering strong sales growth on a raft of new product launches, most notably the anti-VEGF kinase inhibitor anlotinib, which has been swiftly adding indications to its label.
The only US company to make it into the top five mid-cap risers is Seattle Genetics, which is riding high on the prospects for enfortumab vedotin in bladder cancer. The project is filed in a second-line setting, and encouraging data in first-line patients at Esmo this week gave the company a $2bn boost to its market cap.
Notable decliners among the mid-caps include Teva; the Israeli generics giant has yet to solve its myriad of financial woes. Meanwhile Nektar’s concerns are clinical: efficacy of its lead project, bempegaldesleukin, appears to be waning, and investors have declined to swallow the company’s explanations.
Small cap ($250m-$5bn): top risers and fallers in first nine months of 2019

Share price Market capitalisation ($m)
Top 5 risers 9-mth change (local currency) 30 September 2019 9-mth change ($m)
Sosei 203% 1,723 1,182
Eidos Therapeutics 161% 1,347 841
The Medicines Company 161% 3,968 2,554
Arqule 159% 862 560
Spark Therapeutics 148% 3,732 2,255
Top 5 fallers


Inflarx (94%) 64 (879)
Novavax (86%) 120 (584)
Kezar Life Sciences (86%) 63 (388)
Mallinckrodt (85%) 202 (1,114)
Aclaris Therapeutics (85%) 45 (258)
Among the small cap risers, both Eidos and Spark have been the recipients of takeover offers. Eidos’s majority shareholder Bridgebio has been trying to buy the remaining stake in the company, attracted by a that group’s amyloidosis project, but its overtures have been rejected so far. Meanwhile Spark looks likely to fall to an offer from Roche, though drawn out scrutiny by competition watchdogs in both the US and Europe mean this cannot be considered a done deal.
Clinical successes have driven The Medicines Company and Arqule, the former with a novel cholesterol lowering therapy, and the latter in the field of haematological cancers.
Among the small cap fallers, it is mostly clinical failures that have demolished the companies. For Novavax, it was a second phase III failure for its RSV vaccine, Resvax; a post-hoc data dredge failed to convince Inflarx investors that a phase II study of IFX-1 was actually a success; Aclaris’s Jak posted ostensibly positive results but looks unlikely to live up to the competition; while mid-stage data on Kezar’s lupus project, KZR-616, raised safety concerns.
Finally, Mallinckrodt has been taken down by the opioid selling scandal. With the lawsuits claiming compensation far from concluded, the outlook for this company could still worsen.
https://www.evaluate.com/vantage/articles/data-insights/quarterly-shareprice-performance/japanese-drugmakers-stand-out-nine

Keytruda on path to become world’s no. 1 selling drug: research firm

Merck’s (NYSE:MRK) Keytruda cancer drug will be the world’s best selling drug by 2025, with projected annual sales of $22.5B, according to a new report from the GlobalData research firm.
Keytruda already has received 22 approvals for oncology indications by the Food and Drug Administration, and the drug is involved in more than 1,000 clinical trials; if only 10% of those trials hit, approvals for Keytruda will climb exponentially.
While AbbVie’s (NYSE:ABBV) Humira will lose its current top spot for global revenue, it will remain in the top 10 of best-sellers, with GlobalData ranking the drug in 6th place by 2025.
Following Keytruda, Bristol-Myers Squibb (NYSE:BMY) and Pfizer’s (NYSE:PFE) Eliquis is forecast as the second best selling drug, with annual sales of $18.7B by 2025.
Celgene’s (NASDAQ:CELG) – and soon to be BMY’s because of their merger – Revlimid is predicted to take third place, although its worldwide sales will be affected by generic versions, which are set to hit the U.S. market in 2022.
GlobalData sees BMY’s Opdivo, a rival checkpoint inhibitor to Keytruda, coming in fourth place for global revenue, with AbbVie and Janssen’s (NYSE:JNJ) Imbruvica in fifth position.
Rounding out the top 10: Gilead’s (NASDAQ:GILD) HIV drug Biktarvy, Pfizer’s Ibrance, J&J and Mistubishi Tanabe’s Stelara, and Eli Lilly’s (NYSE:LLY) Trulicity.
https://seekingalpha.com/news/3504108-keytruda-path-become-worlds-1-selling-drug-research-firm-says