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Tuesday, September 4, 2018

Open-access plan could spell end to scimed journal subscriptions


Research funders from France, the United Kingdom, the Netherlandsand eight other European nations have unveiled a radical open-access initiative that could change the face of science publishing in two years — and which has instantly provoked protest from publishers.
The 11 agencies, who together spend €7.6 billion (US$8.8 billion) in research grants annually, say they will mandate that, from 2020, the scientists they fund must make resulting papers free to read immediately on publication (see ‘Plan S players’). The papers would have a liberal publishing licence that would allow anyone else to download, translate or otherwise reuse the work. “No science should be locked behind paywalls!” says a preamble document that accompanies the pledge, called Plan S, released on 4 September.
“It is a very powerful declaration. It will be contentious and stir up strong feelings,” says Stephen Curry, a structural biologist and open-access advocate at Imperial College London. The policy, he says, appears to mark a “significant shift” in the open-access publishing movement, which has seen slow progress in its bid to make scientific literature freely available online.
As written, Plan S would bar researchers from publishing in 85% of journals, including influential titles such as Nature and Science. According to a December 2017 analysis, only around 15% of journals publish work immediately as open access (see ‘Publishing models’) — financed by charging per-article fees to authors or their funders, negotiating general open-publishing contracts with funders, or through other means. More than one-third of journals still publish papers behind a paywall, and typically permit online release of free-to-read versions only after a delay of at least six months — in compliance with the policies of influential funders such as the US National Institutes of Health (NIH).
And just less than half have adopted a ‘hybrid’ model of publishing, whereby they make papers immediately free to read for a fee if a scientist wishes, but keep most studies behind paywalls. Under Plan S, however, scientists wouldn’t be allowed to publish in these hybrid journals, except during a “transition period that should be as short as possible”, the preamble says.
Source: Universities UK
“Hybrid journals were always viewed as a step towards full open access. They haven’t succeeded as a transitionary measure,” says David Sweeney, who chairs Research England, one of the funding agencies subsumed under UKRI, the United Kingdom’s national research funder. The plan also states that funders will cap the amount they are willing to pay for open-access publishing fees, but doesn’t lay out what charge would be too much.

Putting the ‘s’ in Plan S

The initiative is spearheaded by Robert-Jan Smits, the European Commission’s special envoy on open access. (The ‘S’ in Plan S can stand for ‘science, speed, solution, shock’, he says). In addition to the French, British and Dutch funders, national agencies in Austria, Ireland, Luxembourg, Norway, Poland and Slovenia have also signed, as have research councils in Italy and Sweden.
“Paywalls are not only hindering the scientific enterprise itself but also they are an obstacle [to] the uptake of research results by the wider public,” says Marc Schiltz, president of Science Europe, a Brussels-based advocacy group that represents European research agencies and which officially launched the policy.

PLAN S PLAYERS

So far, 11 national funding agencies in Europe have signed up to Plan S.
Austrian Science Fund
French National Research Agency
Science Foundation Ireland
National Research Fund (Luxembourg)
Italian National Institute for Nuclear Physics
Netherlands Organisation for Scientific Research
Research Council of Norway
National Science Centre (Poland)
Slovenian Research Agency
Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning
UK Research and Innovation
Smits says he took inspiration from the open-access policy of the Bill & Melinda Gates Foundation, the global health charity based in Seattle, Washington, which also demands immediate open-access publishing. Because Plan S forbids hybrid publishing — and because it involves multiple funders — its impacts could be even more far-reaching than the Gates policy, which by itself has nudged several influential journals to change their publishing models.

Not quite all aboard

Despite Smits’ role, the European Commission hasn’t itself signed the plan. But Smits says that he expects the requirements to be integrated into the terms and conditions of future research grants from the commission. That hasn’t happened yet because policymakers are still debating the details of its next research and innovation programme, Horizon Europe, which begins in 2021 and will be worth €100 billion over 7 years. Smits says he expects more funding agencies to join, and that he will discuss the plan in the United States next month with White House officials, scientific academies and universities.
“The plan is roughly what one would want after about 15 years of funder experimentation with weaker policies,” says Peter Suber, director of the Harvard Open Access Project and the Harvard Office for Scholarly Communication in Cambridge, Massachusetts. “We are very supportive of the ambition set out in Plan S,” adds Jeremy Farrar, director of the Wellcome Trust, a large private biomedical charity in London. He says the funder is finalizing a new open-access policy.
But national research agencies in some of Europe’s leading scientific nations, such as Switzerland, Sweden and Germany, have not yet signed. In Sweden’s case, this is because it has doubts over the tight timetable, says Sven Stafström, head of the country’s research council. He says the council agrees with the aims of Plan S and will review its position on the document at a board meeting later this month. Peter Strohschneider, president of Germany’s national research council, the DFG, says his council hadn’t signed because of the way the plan mandates recipients of public funding to specific forms of open access. “We request our researchers to publish their findings from DFG grants open access but we do not mandate them,” he said. He also cautioned that if researchers were all told to publish in open-access journals, costs of publishing could increase.
Sweeney says that, in the United Kingdom, it isn’t possible to calculate how much funders will need to pay under open-access publishing without a fuller picture of how publishers will respond. “What it costs depends on the reaction of the industry. This is a statement about principles, it is not a statement about [publishing] models,” he says.
And for Stan Gielen, president of the Netherlands Organisation for Scientific Research (NWO), Plan S goes beyond the economics of publishing. “This is part of a bigger transition towards open science and a re-evaluation of how we measure science and the quality of scientists,” he says.

Publisher concerns

Asked for comments ahead of the plan’s launch, publishers said they had serious concerns — particularly around the banning of hybrid journals. A spokesperson for the International Association of Scientific, Technical and Medical Publishers (STM), based in Oxford, UK, which represents 145 publishers, told Nature’s news team that although it welcomed funders’ efforts to expand access to peer-reviewed scientific works, some sections of Plan S “require further careful consideration to avoid any unintended limitations on academic freedoms”. In particular, the STM spokesperson said, banning hybrid journals — which have delivered a lot of growth in open-access articles (see ‘Growth in open access’) — could “severely slow down the transition”. The publishing giant Elsevier said it supported the STM’s comments.
Source: UUK (2017)/BMC Med. 10, 124 (2012).
In another statement, a spokesperson for Springer Nature said: “Research, and the communication of it, is global. We urge research funding agencies to align rather than act in small groups in ways that are incompatible with each other, and for policymakers to also take this global view into account.” Removing publishing options from researchers “fails to take this into account and potentially undermines the whole research publishing system”, the statement added. (Nature’s news team is editorially independent of its publisher).
Meanwhile, the American Association for the Advancement of Science (AAAS), a non-profit organization that publishes the journal Science, said that the model outlined in Plan S “will not support high-quality peer-review, research publication and dissemination”. Implementing the plan would “be a disservice to researchers” and “would also be unsustainable for the Science family of journals”, the AAAS says.
Smits, however, says that it is essential that high-quality peer review remains part of the science publishing system under Plan S. “Publishers are not the enemy. I want them to be part of the change,” he says.

S for sanction?

Only a few funding agencies currently punish researchers who decide not to follow their open-access policies — including the Wellcome Trust and the NIH. But under Plan S, funders promise to “sanction non-compliance”, the initiative states. Smits suggests that a possible sanction for researchers who don’t comply could be withholding the final instalment of a grant, which is usually paid once a project is completed. But this, and other details such as the amount that funders are willing to pay to publish each article, will be worked out by the coalition in the run-up to 2020, he says.
Many European funders have been trying to make research free to read by brokering new ‘read-and-publish’ contracts with publishers, in which a single fee is paid to cover both the costs of reading paywalled research and of authors publishing under open-access terms. But some of the funders who have signed Plan S — including those in the Netherlands and Norway — now say they don’t intend to pay any more subscription fees beyond a transitionary period.
If other funders follow the Plan S idea, it could spell the end of scientific publishing’s dominant subscription business model, says John-Arne Røttingen, the head of Norway’s research council. “Subscription journals will see the opportunity to flip their business models into a system where what is paid for is the solid peer review, editorial reviewing and electronic dissemination of research results,” he says.
But Curry cautions that shifting from a subscription to an open-access business model around the world, as Plan S signers advocate, could bring a new challenge — how scientists in poorer nations will be able to afford to publish open-access work. “That has to be part of the conversation,” he says.

Janssen Submits Nasal Spray Application for Treatment-Resistant Depression


The Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen)today announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for esketamine nasal spray. Janssen is seeking FDA approval of esketamine for treatment-resistant depression in adults.
Esketamine is an investigational, rapidly acting antidepressant that works differently than currently available therapies for major depressive disorder. Through glutamate receptor modulation, esketamine is thought to help restore connections between brain cells in people with treatment-resistant depression.
‘Of the nearly 300 million people who suffer from major depressive disorder worldwide, about one-third do not respond to currently available treatments.3,4 This represents a major unmet public health need,’ said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, LLC. ‘We are committed to working with the FDA to bring this new treatment option to U.S. patients with treatment-resistant depression and to the medical community.’
The NDA is based on five pivotal Phase 3 studies of esketamine nasal spray in patients with treatment-resistant depression: three short-term studies, one withdrawal maintenance of effect study, and one long-term safety study. Data from these studies demonstrate that treatment with esketamine nasal spray plus a newly initiated oral antidepressant compared to placebo nasal spray plus a newly initiated antidepressant was associated with rapid reduction of depressive symptoms and delayed time to relapse of symptoms of depression.5,6 The long-term safety study showed that the esketamine doses studied were generally tolerated, with no new safety signals with dosing up to 52 weeks, compared to data from the short-term esketamine studies.7 The short-term esketamine Phase 3 study in adults with treatment-resistant depression included a newly initiated oral antidepressant in both the control and placebo groups.5
‘Esketamine has been shown to target critical aspects of glutamate-mediated synaptic plasticity, thereby bringing about rapid and sustained improvement in people with treatment-resistant depression,’ said Husseini K. Manji, MD, Global Head, Neuroscience Therapeutic Area, Janssen Research & Development, LLC.
Synaptic plasticity refers to the strength of information that flows through synapses, the spaces where neurons, cells in the brain, are connected.
Esketamine nasal spray will be self-administered by patients under the supervision of health care professionals.
The U.S. FDA granted Breakthrough Therapy Designations for esketamine nasal spray for treatment-resistant depression and for a second indication, major depressive disorder with imminent risk for suicide.8 Janssen is currently conducting Phase 3 clinical studies for the second indication.
Janssen plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for the esketamine treatment-resistant depression indication later in 2018.

As Brexit costs mount, Pfizer estimates $100M to adapt its supply chain


n yet another indication of what the burden of Brexit will be for drug manufacturers, Pfizer has said that it has tallied its costs to revise its manufacturing and supply chain at about $100 million.
In a quarterly filing, the New York-based Big Pharma player said that its “preparations are well advanced to make the changes necessary to meet EU legal requirements after the U.K. is no longer a member state, especially in the regulatory, manufacturing and supply chain areas,” so that it can ensure a continuity of supply in the U.K. and Europe.
“The one-time costs of making these adaptations are currently estimated at approximately $100 million,” Pfizer said.
According to Bloomberg, which first reported the Pfizer figure, GlaxoSmithKline has also estimated its Brexit costs at about $100 million. Smaller company AstraZeneca has pegged its costs at about $40 million.
With a deal between the U.K. and the EU on how to have an orderly separation nowhere in sight, drugmakers have been mapping out their own plans on how to avoid backups and shortages in supplying drugs from one market to the other after the divorce in March of next year.
Anticipating delays at border crossings, French drugmaker Sanofi is considering flying vaccines, which have a short shelf life, to a predetermined spot in the U.K. where the government would release the delivery instantly. Another option, if the two sides could agree, would be to mark trucks so that they can pass customs without the usual checks.
Sanofi has already said it was increasing its inventory of drugs for the U.K. from the usual 10 weeks to 14. AstraZeneca has also said it is stockpiling drugs supplied by the U.K. and EU for each other. Merck & Co. is making its own plans, including reserving as much as six months’ worth of product in the face of a possible “temporary supply blackout” next March.
But the U.K.’s National Health Service wants to ensure that all drugmakers are prepared for the worst. Last week, it ordered drugmakers to report by Sept. 10 how they will stockpile in the U.K. those medications currently made in Europe but sold to the National Health Service. It wants at least six weeks’ worth of supplies above their regular buffers.
“While we recognise that many companies will already have made their own arrangements we are keen to receive a response from all companies to ensure we have a comprehensive picture. … We are asking suppliers to confirm their plans on a product-by-product basis,” the report says.

Cipla, Zydus Cadila and more eye $1B deal for Bharat Serums


Several Indian biopharma companies are eyeing a potential buy of Bharat Serums and Vaccines in a deal that could be worth $1 billion, according to The Economic Times, which cites two sources familiar with the talks. Price remains a key stumbling block.
Among potential buyers are Cipla, Zydus Cadila and Dr. Reddy’s Laboratories, plus private equity fund Baring Asia, according to the publication.
Two private equity funds—Kotak Private Equity and Orbimed Asia—hold 23% of the biologics company, while the Daftary family owns the rest. The owners have hired Jefferies to manage the sale, but the discussions are in early stages. Price is considered a hurdle to the deal, according to industry experts cited by TET.
Bharat Serums and Vaccines has more than 900 employees worldwide and operates in more than 45 countries. Founded in 1971, the company sells meds in gynecology, assistive reproductive technology, critical care, neurology, nephrology and more. The drugmaker owns two subsidiaries: BSV BioSciences, a California R&D outfit working on early-stage development of recombinant molecules, and a German branch that manufactures and markets biological APIs.
Last year Mylan entered talks for a potential purchase of Bharat Serums, but the deal didn’t materialize.

Merck gets partial refusal on Keytruda in lymphoma from NICE cost watchdogs


Just one week after England’s National Institute for Health and Care Excellence (NICE) said no to Gilead’s CAR-T treatment Yescarta in non-Hodgkin lymphoma, it has decided that Merck’s blockbuster checkpoint inhibitor, Keytruda, is not a good treatment choice in Hodgkin lymphoma—at least not for all patients.
NICE published a guidance document on Monday suggesting that Keytruda should not be used in patients with relapsed or refractory Hodgkin lymphoma who have already been treated with both the chemotherapy drug Adcetris and an autologous stem cell transplant. It did recommend the drug for use on its Cancer Drugs Fund in patients who are not eligible for stem cell transplant.
The reason for the split decision? NICE said it currently recommends Bristol-Myers Squibb’s rival checkpoint inhibitor, Opdivo, for treating relapsed or refractory Hodgkin lymphoma after Adcetris and stem cell transplant. Physicians suggested to NICE that the cost-effectiveness of Keytruda (pembrolizumab) would likely be similar to that of Opdivo (nivolumab), but Merck did not provide head-to-head data in patients who had received stem cell transplants, according to the decision.
“The committee noted that the company had not provided evidence to demonstrate different clinical efficacy between nivolumab and pembrolizumab, or provided a convincing explanation as to why the treatment effects would be likely to differ,” the agency wrote.
Merck did not immediately respond to a request for comment from FiercePharma. Keytruda is approved in the U.K. as a solo therapy in patients with Hodgkin lymphoma who have either failed stem cell transplant or are ineligible for it.
The company provided economic models for Keytruda in Hodgkin lymphoma patients who had failed stem cell transplants, but NICE found them to be faulty. Merck’s package for NICE included data from a trial showing an improvement in progression-free survival and objective response rate in both subsets of patients, but it wasn’t clear how big an effect it was. The company also initially forecast that stem cell transplants would happen 12 weeks after patients started their treatments—an inappropriate assumption, NICE said, because the effort to find stem cell donors almost always causes a delay in the procedure.
So Merck revised the model, assuming that all transplants would happen 24 weeks after treatment. NICE quibbled with the company’s methodology, though, ultimately deciding that conclusions about overall survival benefits from Keytruda in patients undergoing stem cell transplants were “likely to have been overestimated in the model,” the guidance document said.

The exclusion of Keytruda after stem cell transplant from the NHS’ list of covered drugs could dampen what has been an impressive run from Merck in the ongoing rivalry with BMS. In the second quarter, Keytruda hauled in $1.67 billion in total sales, surpassing Opdivo’s $1.63 billion in sales in the same period. It was the first time Keytruda beat Opdivo in the market for PD-1/L1 inhibitors.
Merck has scored some key wins for Keytruda that are helping fuel its strong run. In August, for example, the FDA expanded the drug’s label to say that when it is combined with Eli Lilly’s Alimta and platinum chemo in patients with treatment-naïve non-small cell lung cancer, it cuts the risk of death by 50% over chemo alone. Merck has the distinction of having the only checkpoint inhibitor that’s approved in the U.S. in the first-line lung cancer setting. And in July, the European Medicines Agency’s (EMA) recommended the combo, too.
Just how big an effect the NICE rejection in Hodgkin’s lymphoma will have on Keytruda remains to be seen. But one thing can be said for certain: England’s cost-effectiveness watchdogs are clearly not welcoming the pricey new generation of immuno-oncology treatments with open arms. That was evident in NICE’s rejection of Yescarta, which came immediately after the personalized cell therapy was approved in Europe to treat relapsing diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma.
NICE didn’t disclose Gilead’s planned price of Yescarta in the U.K., saying only that the product lacks “plausible potential to be cost-effective.” Gilead is in discussions with the agency and hopes to reach an agreement that will reverse the decision.

UnitedHealth price target raised to $304 from $270 at Credit Suisse


Credit Suisse analyst A.J. Rice raised his price target for UnitedHealth to $304 from $270 after surveying 737 health benefit managers across the country to gain insight into market perceptions regarding national health insurers, cost trends, premium expectations, and employer priorities heading into 2019. The analyst notes that the survey bodes well for his MCOs coverage. He reiterates an Outperform rating on the shares.

DelMar Pharmaceuticals Appoints Oppenheimer as Strategic Advisor


DelMar Pharmaceuticals, Inc. (Nasdaq: DMPI) (“DelMar” or the “Company”), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, today announced the appointment of Oppenheimer & Co. Inc. to serve as its strategic advisor. In this capacity, the firm will work on behalf of DelMar to manage the exploration and evaluation of a wide range of strategic opportunities with the goal of facilitating shareholder value generation.
“We believe that seeking a strategic transaction gives us the best opportunity to maximize shareholder value,” said Robert E. Hoffman, Chairman of the Board of Directors. “In addition, we continue to be dedicated to executing our ongoing Phase 2 trials for MGMT-unmethylated GBM patients at MD Anderson Cancer Center in Houston, Texas, and at Sun Yat-Sen University Cancer Center in Guangzhou, China.”
While the Company is evaluating strategic opportunities, there can be no assurance that this strategic review will result in a transaction.