UnitedHealth to acquire payments firm for $3.2B

UnitedHealth Group (NYSE:UNH) has agreed to a $3.2B deal to acquire payments firm Equian, The Wall Street Journal reports.

It would likely merge Equian into its rapidly growing Optum health services unit, a move that would help Optum branch out beyond healthcare considering Equian’s broader client base.

Equian is owned by private-equity firm New Mountain Capital.

https://seekingalpha.com/news/3472878-unitedhealth-acquire-payments-firm-3_2b-wsj

Preeclampsia Has Increased Risk for Stroke. Can Aspirin Help?

At the 2019 American Academy of Neurology’s annual meeting in Philadelphia, Eliza Miller, MD, of NewYork-Presbyterian Hospital/Columbia University Medical Center, presented her study which sought to determine whether hypertensive disorders of pregnancy increased the long-term risk for stroke in women. In addition, she and her colleagues examined whether statin or aspirin use modified this risk.

Miller discusses her study in this exclusive MedPage Today transcript of her remarks:

This was a study that we conceived of because I was seeing in my practice a lot of women in middle age, in their 40s, 50s, early 60s, who were coming in with stroke. Many of them did have cardiovascular risk factors, but a lot of them had this history of having had preeclampsia in a prior pregnancy. I’m very interested in preeclampsia and its cardiovascular and cerebrovascular risks, both in the short term and the long term. We know from a lot of other literature that women who have had preeclampsia in their pregnancies have a heightened cardiovascular risk in general. They have a greater risk of developing chronic hypertension, greater risk of developing heart failure, myocardial infarction, and stroke.

The question is should these women be treated differently with primary prevention since preeclampsia occurs at a young age. It’s usually women in their 20s and 30s who are having babies, for the most part, and that’s usually when women develop preeclampsia. This is kind of an opportunity to identify women who may be at really increased risk long term. Unfortunately, a lot of the prospective cohort studies that have looked at cardiovascular risk, including stroke, have not really included the obstetric history as part of the questions that they ask in their questionnaires. For example, the Framingham study, where a lot of our risk scores come from that study, did not include that in their history. The original Nurses’ Health Study, which is another really important study of cardiovascular risk, also didn’t include it. The Women’s Health Initiative also didn’t include it in their questions.

But there are a few studies that did, and one of them is the California Teachers Study, which has been going since 1995 and studied over 100,000 teachers in California prospectively over that period of time. To their credit, they did ask about obstetric history early on, so we knew whether these women at least had self-reported a history of preeclampsia, and then followed over time, we knew what medications they were taking, including aspirin, including statins, anti-hypertensives. Then we knew the outcomes because those are tracked through the California Teachers Study, including stroke and TIA and other cardiovascular outcomes as well.

We took a look just to see whether the women who had early on identified themselves of having this history of preeclampsia and then went on and, for whatever reason, were put on aspirin as primary prevention before having had any cardiovascular event, if that would lower their risk of stroke. What we found was interesting, which was that first of all, overall, a history of preeclampsia — even after adjusting for all the other risk factors — did increase the risk of future stroke overall, about 30%, even after adjusting for everything. But in the younger group, I was particularly interested in stroke before the age of 60 because that’s what I’d been seeing in my practice. In that younger group, what we saw was that the women who were not taking aspirin had about a 50% increased risk of having a stroke before the age of 60, but the women who were, for whatever reason, taking aspirin, that risk was no longer there. They didn’t have any increased risk.

That was very thought provoking for me, and I do not think that this means that we should be putting everybody on aspirin if they’ve had preeclampsia because there are risks to putting people on aspirin, and the benefit may not outweigh those risks, but there may be certain very high-risk people. For example, women who have preterm preeclampsia, which is especially high risk. That’s preeclampsia that happens before 34 weeks of gestation. We know that those women have a very heightened risk of cardiovascular events, including stroke, later in life. It could be that those women might benefit. Really the only way to know is to do a randomized trial, so this is observational data and we can’t change our practice based on that, but it’s certainly thought provoking and hypothesis generating for a future trial.

I would love to be in the trial business. I don’t think we’re quite ready for prime time, but I think that is something that would be worth doing.

One of the things that’s interesting is that these are younger women we’re talking about, so they are of childbearing age, and you can’t give clopidogrel to women who are pregnant, and you can give aspirin to women who are pregnant. In fact, one of the reasons I was interested in aspirin, particularly, is that women who are at risk for developing preeclampsia are actually put on aspirin during their pregnancies to reduce that risk. It reduces the risk of getting preeclampsia by about 50% in high-risk women. That’s a safe drug that can be given during pregnancy.

That said, aspirin is not a no-risk medication and we know from recent publications in the New England Journal of Medicine that there are risks to aspirin, GI bleeding, intracranial hemorrhage, all of these things can be a consequence of taking aspirin. You don’t want to just give it to just everybody. What we really need is more of what we would call a precision-medicine approach, where we identify the people that would be at the highest risk and could get the most benefit from taking it, and then give it only to those people.

https://www.medpagetoday.com/meetingcoverage/aanvideopearls/80551

FDA Panel Against Cutting Paclitaxel-Coated PAD Device Access

The late mortality signal of paclitaxel-coated devices used in peripheral artery disease (PAD) shouldn’t force these balloons and stents off the market, a panel concluded at an FDA advisory committee meeting here.

Citing a totality of evidence that still weighs heavily in favor of benefits from these devices — improved quality of life and reduced need for repeat revascularization for PAD, none of the panelists suggested restricting or eliminating access.

Yet they also judged the excess mortality risk as real, no matter the low quality of the available data. And this should be communicated carefully to healthcare practitioners and the public, the panelists said.

Todd Rasmussen, MD, of Walter Reed National Military Medical Center in Bethesda, Maryland, for example, said he accepted the finding of a late mortality risk that was first proposed last December.

“However, regarding the magnitude, I find these findings statistically significant but not practically significant. As I sit in my office and talk to my patients, I would not underestimate our patients’ ability to assess and access data and make their own decision.”

Patients may choose not to undergo an intervention at all if their disease is not limb-threatening and they help themselves with some exercise therapy, suggested Frank LoGerfo, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston.

“We need to learn how to communicate a short-term benefit that is certain against a long-term risk that is uncertain,” said Michael Krucoff, MD, of Duke University School of Medicine in Durham, North Carolina.

What mechanism could be behind device-related deaths remains unclear. But just because it’s not clear right now doesn’t mean it doesn’t exist, some suggested.

Paclitaxel has been used for decades as a chemotherapy medication. The drug kills cells at high doses; at lower concentrations, it inhibits arterial smooth muscle and endothelial cell proliferation.

“What we’re seeing is maybe a trend that crescendos at 5 years,” commented John Somberg, MD, of Rush University Medical Center in Chicago. “That can’t be dismissed just because there’s not a mechanism. Lots of things occur where subsequently they find [it].”

Krucoff recalled his years in residency before people realized what AIDS was, when infections and cancers blossomed, and how it took decades to put together that there was an immune system condition that manifests differently in different people.

In PAD, the lag time of 2 to 5 years to see an uptick in deaths among paclitaxel-coated balloon and stent recipients suggests the development of new disease, Krucoff emphasized.

Short of performing the 32,000-person trial that the FDA said it would take to exclude a mortality signal over 5 years with good statistical power, panelists suggested close collaboration among device companies and the FDA to pool their resources and speed up post-market data collection.

Accruing more 5-year data is mandatory for the understanding of the mortality risk, they added.

And as existing animal data don’t provide mechanistic insights, new animal studies are “absolutely essential” going forward — and it would be preferable that researchers get creative, added Joaquin Cigarroa, MD, of Oregon Health & Science University in Portland.

https://www.medpagetoday.com/cardiology/pci/80620

Pfizer, AZ and more under threat as China solicits generics

The U.S. FDA compiles a list of off-patent drugs without an approved generic to encourage the development of copycats. Now, the Chinese authorities are rolling out a similar initiative, only with some extra incentives.

On Thursday, China’s National Health Commission published (Chinese) its first proposed list of 34 drugs (full list below) that the agency says are already off patent or nearing patent expiration but have no generic drug application in the country or lack competition. The plan is to invite drugmakers to make copies—and here comes the key—under drug regulator’s priority review pathway, which was until now only given to innovative drugs.

The list covers originators from many foreign pharmas, including Pfizer, AstraZeneca, Merck & Co., Johnson & Johnson, Roche, Bristol-Myers Squibb, Takeda, Eli Lilly, and more. And the drugs span a wide range of therapeutic areas, including HIV, anti-infectives, ophthalmology, cancer, blood and immune disorders, etc.

Some prominent names can be found on the list.

Teva’s multiple sclerosis blockbuster Copaxone, which just saw its first U.S. copycat from Mylan less than two years ago, is probably the best-selling drug on the list by global sales. Johnson & Johnson subsidiary Actelion’s pulmonary artery hypertension drug Tracleer and United Therapeutics’ rival med Remodulin are both included. Roche’s CMV retinitis treatment Valcyte and chemotherapies Faslodex and Ixempra from AZ and BMS, respectively, are also among those listed.

China made certain of its intention to make that list in January. At that time, it said the government would update the list at the end of each year starting from 2020. And key small molecules and biologics on the list will also be incorporated into state-backed R&D plans.

The initiative is seen as another push by the Chinese government to bring in competition to rein in drug costs. In a recent decree, physicians are strictly not allowed to write brand names on prescriptions, and even if they do, pharmacists could fill them with generics.

Multinational firms have for a long time enjoyed strong sales from their older medicines in China, even as they suffer in developed markets like the U.S. and EU. But in a bulk procurement program being piloted in 11 major cities, these foreign bigwigs have started to feel the heat. With the scheme, drugmakers—originator and generic—bid for big supply contracts with all public hospitals in those cities. Of the final 25 contracts, foreign pharmas only won two.

Pfizer, which lost out to domestic makers with Lipitor, and AstraZeneca, which failed in its attempt at winning the Crestor tender, are both guiding slower China sales growth this year.

For the current 34-drug list, the Chinese government is opening up for public comments for five work days.

Full list of the 34 drugs by generic name:

abacavir, alcaftadine, atovaquone, azathioprine, bosentan, brivaracetam, colesevelam hydrochloride, cyclophosphamide, dapsone, deferasirox, dofetilide, eletriptan, ertapenem, fezoterodinum, formoterol fumarate, fosaprepitant, fulvestrant, glatiramer, icatibant, ixabepilone, levodopa/benserazide, levothyroxine, mercaptopurine, methotrexate, nitisinone, posaconazole, pyridostigmine, raloxifene, rilpivirine, tafluprost, tretinoin, treprostinil, valganciclovir, vigabatrin.

https://www.fiercepharma.com/pharma-asia/foreign-drugmakers-under-threat-as-china-rolls-out-drug-list-to-boost-generic

Merck CEO sees legal issue if US adopts drug pricing based on other nations

Merck & Co Chief Executive Ken Frazier said on Thursday a rule to base the price the U.S. government pays for some prescription drugs in it Medicare program on lower prices in other countries would face legal challenges if adopted.

U.S. President Donald Trump said last year that one way his administration would seek to lower drug costs to consumers could be through an international pricing index (IPI) that would determine what Medicare pays for certain medicines based on the prices set in a handful of other countries. A proposed version of the rule is expected in August.

Other developed nations with single payer systems typically pay far less for drugs than the United States, which Trump called “global freeloading.”

“I think there will be challenges to the rule,” Frazier told reporters following the drugmaker’s investor day in New York. “A lot of people have objections to that rule. It’s not just pharmaceutical companies.”

Frazier, a lawyer by trade, did not say whether Merck would launch its own legal challenge to the proposed rule.

The company was one of three U.S. drugmakers that sued the U.S. Department of Health and Human Services this week over a new government regulation requiring them to disclose the list price of prescription drugs in direct-to-consumer television advertisements.

Of the Trump administration proposals to lower drug costs, the IPI option is the one Frazier said most concerns him, due to the effect importing price controls from other countries might have on innovation and patient access in the United States.

“We tell incomplete stories about those markets,” Frazier said, noting that some countries ration treatments available to patients. He pointed to lower survival rates for lung cancer in Britain, which has an agency that can bar the use of approved new medicines based on their cost.

Earlier on Thursday, Merck executives touted the company’s pipeline of experimental drugs beyond its blockbuster cancer treatment Keytruda.

The investor event was also an opportunity for Merck to showcase executives other than Frazier, who turns 65 in December. Last year, the company scrapped its mandatory retirement age of 65 for its CEO, saying it gave the board flexibility around finding his successor.

“I’m extremely pleased by the breadth of the leadership talent at the company,” Frazier said in response to a question about succession. “I know that the board feels the same way. And they will continue to look at when the right opportunity is … to make a selection.”

https://www.marketscreener.com/MERCK-AND-COMPANY-13611/news/Merck-and-CEO-sees-legal-challenge-if-U-S-adopts-drug-pricing-based-on-other-countries-28790634/

J&J moves to strike Okla. witness as ‘de facto member of State’s legal team’

Johnson & Johnson has asked the judge overseeing the first in an expected wave of trials against the opioid industry to strike the testimony of Dr. Andrew Kolodny, a psychiatrist who plays a central role in the State of Oklahoma’s case by linking narcotics marketing to opioid addiction and overdose deaths.

Calling Dr. Kolodny “a de facto member of the State’s legal team,” J&J said Oklahoma gave the Brandeis University researcher unfettered access to some 90 million internal documents obtained through discovery and used his expert testimony to “pollute the trial record with rampant hearsay, rank speculation, and the State’s own take on the evidence.”

Experts like Dr. Kolodny play a crucial role in the opioid litigation, since the plaintiffs – mostly states, cities and counties claiming to be seeking to recover opioid-related expenditures – appear to have settled on a strategy of “aggregate proof” under which they will present expert testimony, instead of specific examples, to show a connection between pharmaceutical industry practices and the increase in opioid abuse.

Defendants like J&J therefore have a strong incentive to knock out these expert witnesses as unqualified.

Over five days on the stand, Dr. Kolodny touched on every element of Oklahoma’s case, including extensive testimony about how J&J’s ownership of a wholesale opioid ingredient business in Tasmania made it the “kingpin” of the opioid industry. Kolodny, co-director of Opioid Policy Research for the Brandeis University Heller School for Social Policy and Management in Massachusetts, also accused J&J of funding pain-treatment organizations and other groups he termed an “opioid Mafia.”

In Dr. Kolodny’s pretrial deposition, taken two days after Oxycontin-manufacturer Purdue Pharma settled with Oklahoma, J&J says the physician for the first time discussed how the company’s Noramco and Tasmanian Alkaloids businesses “were the true cause of the opioid crisis,” instead of the widespread distribution of Oxycontin.

The only opioid products J&J sold in Oklahoma were Duragesic, a fentanyl patch its Janssen unit introduced in 1991, and Nucynta, a pill it began selling in 2009. The company’s products represented less than 1% of Oklahoma Medicaid opioid prescriptions from 1996-2017.

Kolodny later testified in court that Purdue Pharma and its founding Sackler family “have been stealing the spotlight, but Johnson & Johnson, in some ways, has been even worse.” He also intimated, without specifically saying so, that J&J had coordinated with Purdue to produce a new strain of poppy rich in thebaine, a type of opioid, to supply expected rising demand for Oxycontin.

“This extended, free-form commentary about the State’s evidence over which the witness lacks both personal knowledge and expertise is not testimony at all, much less expert testimony,” J&J said in its filing. “It is advocacy, nothing more.”

No one from the office of Oklahoma Attorney General Mike Hunter was immediately available to comment. Kolodny testified he has been working as a paid expert for Oklahoma nearly full-time with the state for months. In testimony, he said his fee is in the mid-six figures.

Expert witnesses are intended to present opinions on complex matters to help the finder of fact, either a judge or jury, determine which party’s case is closer to the truth. Judge Thad Balkman has thus far refused most of J&J’s requests, perhaps most significantly refusing to put the case before a jury even though the state is seeking $17 billion in damages to clean up its opioid-related problems.

Judge Balkman agreed with the State that the $17 billion isn’t money damages, which would require a jury trial if the defendant so wished, but money for “abatement” of a public nuisance.

The state’s case is based upon a simple theory, reiterated throughout the trial by lead plaintiff lawyer Brad Beckworth, a private attorney whose firm has already reaped part of the $59 million in fees awarded in Purdue’s settlement with Oklahoma: “If you oversupply, people will die.”

The State says opioid abuse was rare until 1996, when Purdue launched Oxycontin with the help of J&J’s wholesale opioid unit. It is calling experts like Kolodny to establish the cause-and-effect relationship, although it is not expected to call a single physician who relied on improper marketing to overprescribe opiates, or a single patient who received medically unnecessary opiates.

The state’s other expert witnesses have also displayed a thorough knowledge of their client’s case. In testimony yesterday streamed online by Courtroom View Network, Dr. Jason Beaman, chair of the psychiatry department at the Oklahoma State University Center for Health Sciences, mentioned another key legal talking point for the plaintiffs when he described the state’s “indivisible” injuries. Under Oklahoma’s rules for joint and several liability, J&J could be liable for the entire $17 billion opioid abatement tab if Judge Balkman finds its contribution to the crisis was indivisible from the activities of Purdue and other companies.

https://legalnewsline.com/stories/512646956-at-opioid-trial-johnson-johnson-moves-to-strike-oklahoma-witness-as-de-facto-member-of-state-s-legal-team

Dueling Numbers: FDA Panel Probes Paclitaxel-Coated Stent, Balloon Safety

The U.S. Food and Drug Administration (FDA)’s Circulatory System Devices Panel is in the middle of two days of presentations and meetings regarding mortality rates associated with the use of paclitaxel-coated balloons (DCBs) and paclitaxel-eluting stents (DESs). The discussions are noting missing data and conflicting analysis.

Paclitaxel is a drug that has been used on coating stents and balloons since 2003 and has expanded over the last decade. The stents and balloons are used to treat peripheral arterial disease (PAD) in the femoropopliteal artery. The balloons and stents mechanically open the restricted or blocked vessels. Paclitaxel is released from the balloon or stent to prevent formation of scar tissue in the blood vessel.

It was a December 2018 publication of a meta-analysis that launched the controversy. The research was led by Konstantinos Katsano of Patras University Hospital, Rion, Greece. The analysis looked at data from 28 randomized controlled trials, which found an increased risk of all-cause mortality starting at two years and running out to five years for patients treated for femoropopliteal artery disease using a paclitaxel-coated balloon or stent compared to a device without a coating.

The panel is chaired by Richard Lange of Texas Tech University Health Sciences Center, El Paso. The advisory committee’s job is to make formal recommendations to the agency on various topics, including potential regulatory actions concerning devices already on the market as well as those in clinical trials.

The current two-day meeting launched with FDA reviewers and statisticians is discussing the current data and their attempts to round it out by requesting mortality data and information on patients that were lost in follow-up studies.

“The agency said today that some of the manufacturers, in the interim, have provided missing data, such that the percentage of five-year mortality data still missing now ranges from 2.7% to 26% across the pivotal paclitaxel DCB studies, down from as high as 40% a few months ago,” reported tctMD/the heart beat.

However, an FDA cause-of-death analysis continues to show cardiovascular and non-cardiovascular-related deaths of all types excluding infections to be higher in the patient groups using paclitaxel DCB and DES compared to those receiving uncoated devices. They haven’t found any data among the groups that explain the numbers.

During the session, FDA representatives were not always able to answer questions from the committee because of either lack of data or not enough time to analyze new data they had received. FDA advisor John W. Hirshfeld Jr., of University of Pennsylvania Medical Center in Philadelphia, referred to it as “a forest of dueling numbers.”

“The problem is that the numbers presented by industry and the numbers presented by FDA are not the same,” Hirschfeld continued. “As a consequence of this, we have a conundrum in trying to decide what weight to place on each analysis that we see. What I would hope would be that there would be a way … to get a common agreement about what the real numbers are between the sponsors and the agency so that we know exactly what data we’re dealing with.”

Industry representatives also spoke and introduced data, arguing that their own data doesn’t show the same mortality signals seen in Katsanos’ meta-analysis. Katsano also spoke, reviewing some of the criticisms of his research study. He pointed out that the only device manufacturer to provide patient-level data for more research was Cook Medical. And using that data, which derived from the ZILVER PTX trial, Katsanos demonstrated a negative interaction between paclitaxel and other risk factors, showing that the risk of death was highest for patients with the fewest risk factors and lowest for patients with the highest number of risk factors. He concluded that patient risk-stratified analysis was worthwhile to guide medical decisions.

In the midst of the panel debate before questioning, they appeared to agree across the board that a mortality signal does exist. What isn’t as clear is whether it should matter to clinicians and patients.

“The lack of practical significance is especially important in light of the technology’s potential to improve quality of life versus surgery,” stated Todd E. Rasmussen, of Walter Reed National Military Medical Center in Bethesda, Md.

The panel discussions continued today.

https://www.biospace.com/article/fda-struggling-to-make-determination-on-paclitaxel-pad-devices/