Medical journals raise concerns about data in two studies related to Covid-19

Two of the world’s leading medical journals on Tuesday expressed concern about potential flaws in the data produced by a small company to draw major conclusions about Covid-19 — that certain heart drugs are safe, and that the malaria drug hydroxychloroquine is not. The latter finding led to the pause of an important study of hydroxychloroquine by the World Health Organization.
“Serious questions have been raised about the reliability of the findings reported in this paper,” Richard Horton, the editor of the Lancet, where the hydroxychloroquine study was published, wrote on Twitter.
Eric Rubin, the editor of the New England Journal of Medicine, which published the study of heart drug safety, struck a similar tone.

“Substantive concerns have been raised about the quality of the information in that database,” Rubin wrote in the so-called expression of concern published by the journal. “We have asked the authors to provide evidence that the data are reliable.”

The concerns, which have built over the past several days on social media, highlight larger issues with using big databases to draw conclusions about medicines, an approach that has been gaining rigor in the era of big data. Experts warn that conducting such studies properly is far more difficult than it appears.

“This is not for the faint of heart,” said Harlan Krumholz, director of the Center for Outcomes Research and Evaluation at Yale-New Haven Hospital. “This is not just a matter of dial-a-study when you get access to data. Well-done studies are based on understanding the provenance of the data and making sure what you are doing is reasonable. There is good science to be done with big databases, but there are also major mistakes to be made. The question is: what happened here?”
Both studies in question used data from Surgisphere, a little-known company based in Chicago that claimed in the Lancet study to have data from 671 hospitals on six continents. The Lancet paper found that the malaria drugs chloroquine and hydroxychloroquine, which had been explored as potential therapies for Covid-19, did not correspond with improved outcomes for patients, and were also associated with higher mortality. The paper in the New England Journal of Medicine reported that blood pressure medications were not associated with worse outcomes in patients with Covid-19. The studies share some of the same authors, including Sapan Desai, who runs Surgisphere.
After suspending the clinical trial arm focused on hydroxychloroquine, the WHO said it would review the data generated so far. That portion of the WHO’s multi-drug Solidarity Trial remains paused, delaying answers on a drug that has become a political flashpoint even as the evidence on its potential benefits and risks is murky.
But news reports and experts have raised questions about the integrity of the Surgisphere data. The Guardian, for example, reported on discrepancies in data said to come from Australia in the Lancet study. The Lancet study’s authors have corrected errors about the number of participants, but have stood behind their conclusions.

Outside experts, however, have raised broader concerns. In a May 28 letter to the editor of the Lancet and the study’s authors, more than 180 scientists outlined questions about the statistical analysis and a lack of transparency. The study’s authors did not release the full data underlying the study and did not say which countries or hospitals contributed data, the letter says. The outside scientists called on Surgisphere to at least provide details about how it sourced its data and called for an independent validation of the analysis.
The study’s authors agreed to an independent audit of the source of the data and the analysis.
On Tuesday, the group of concerned researchers also wrote to the editor of the New England Journal, raising “similar issues” as they had seen in the Lancet paper. One issue, according to the letter: In some countries, “a relatively small number of hospitals are reported to have provided electronic patient record data to Surgisphere, yet these reports describe a remarkably high proportion of all PCR-confirmed cases in the respective countries.” They flagged specific concerns with data purported to come from the United Kingdom and Turkey.
The Lancet and New England Journal separately on Tuesday issued their expressions of concerns.
In their notice, the Lancet’s editors said the independent audit of the data were “expected very shortly” and noted the “serious scientific questions” that had been raised.
Surgisphere did not immediately respond to a request for comment. In a statement on its website after criticisms were raised about the Lancet study, it highlighted “the validity of our database.” It said its registry was based on electronic health records from customers of its machine learning program and data analytics platform, which allow the company to in turn use data from the records to study “real-world, real-time patient encounters.”
“Together, we stand behind the integrity of our studies and our scientific researchers, clinical partners, and data analysts,” the statement said.
The results of the hydroxychloroquine and chloroquine study in particular grabbed attention, as the drugs’ potential as Covid-19 treatments has become politicized. President Trump and his allies have touted their purported benefits, even as no gold-standard clinical trials have yet produced results and observational studies cast doubt on their efficacy. Trump said he was taking hydroxychloroquine to try to protect himself from the coronavirus.
But there have been concerns raised about the potential side effects of the drugs in people with Covid-19; the Food and Drug Administration, for example, has said it should not be used outside of clinical trials or for patients who are not hospitalized, because of the risk it poses to heart health. Trump’s critics used the Lancet study to argue that by promoting the drug, the president had been endangering the public.

Top medical journals raise concerns about data in two studies related to Covid-19

Interview With Biologist Erin Bromage

When biologist Erin Bromage posted a blog about reducing personal risk for contracting COVID-19, little did he realize that he was about to become very well known. His ability to turn complex scientific principles into clear guidance for action has clicked with millions of people. Medscape spoke with Bromage about the COVID-19 blogs read round the world, and what he foresees for the country moving forward. This interview has been edited for length and clarity.

Which of your posts got the most attention, and why do you think that happened?

I wrote a post called The Risks – Know Them – Avoid Them. I was writing it for my friends and family in Australia and here in the United States. Both countries were about to reopen, but no one had any idea of where to put our energy with respect to risk mitigation or hazard reduction behavior.
So I put together a story: this is what we know, this is what it means, and this is what we can do. It seemed to gel. I think it’s because I could simplify the information that was out there. It’s helped a lot of people visualize the risks.
I work in infectious diseases, but mainly with animals. I had been keeping a close eye on the virus since early January. Come February, I started seeing things that made me realize that this is going to change our lives. So I started putting little snippets out to friends on Facebook. After eight or 10 of those posts, one of my friends asked me to put them on a website so everyone could read them.
When I wrote about things like grocery shopping or whether pets can transmit the virus, I’d get a couple of thousand people reading my posts. Then about a month ago I wrote the post about risks, looking at all the data and what it would mean for summer going forward.
I posted it on a Wednesday night, and when I woke up in the morning, it had about 8000 views. By the end of Thursday night it was closer to 200,000. I reached out to my university and said, “Help — I don’t know if I’ve done something wrong.” They gave me the help I needed, sort of a buffer around me because I was getting a lot of requests.

Over that first weekend it ended up getting seen by 6 million people. The mention in the New York Times made it explode. It’s now had about 18 million views on my site and another 5 to 7 million on hosting sites in different languages.

Your blogs have been praised by neuroscientists, physicians, business owners, teachers, and many others. Yet, you say that you aren’t an expert in these topics. Where do you get your information, and how do you decide what to write about?

No one could possibly claim to be an expert in all the disciplines contributing to the knowledge on SARS-CoV-2. My training in infectious diseases and immunology helped me understand the science outside of my specialty, but one of the most revealing mediums I found was #epitwitter — a group of epidemiologists on Twitter discussing in real time their findings, the findings of others, ideas, and where the science was going.

They would say, “Hey this paper came out today and this is significant.” You could see from the minds of about 80 people where the most important papers were in the field and what the collective mind was thinking. It’s an incredible opportunity to watch some of these amazing virologists, epidemiologists, and public health experts all coalesce on a single problem and then take that information and put it into something that’s relevant.

In your blogs, you use math to illustrate what happens in different social situations, adding the variable of time. How does time influence risk?

I was more attuned to this is because I do infectious dose work quite regularly in my lab. When we do experiments with animals, there is a really strong factor with dose and time. You can give high dose over a short period and the result is severe disease. You can give a low dose over an extended period and end up in the same situation, and then there’s everything in between.
So exposure is not this one-off circumstance. Exposure can come in many different ways, and there are even more nuances. There are different infectious doses that happen between your eyes, your nose, and your lungs that affect things differently. We do the same thing with animals. If you give a dose intranasally, it’s very different from just putting it into the air for an extended period of time.
I was very interested in dose-time, and I didn’t think most of the general public was aware that that was an important factor. People were having a hard time trying to understand contact tracing situations. You might be contacted if you had been in contact with an infectious person and speaking with them for 10 or 15 minutes, but they didn’t know why. Why not 5 minutes? Why did it matter if you were in the same environment as them for a half hour or an hour, but not 15 minutes?

When I was able to put all that together — that it’s exposure to virus and time, you get to the same results by different pathways — I think the light went on for a lot of people. This is why splashguards went up in grocery stores. This is why the bus drivers are getting sick in NYC, because they are getting a low dose over an extended period of time.
So it started to make sense to everyone about why we are being told to do things or not do things and how it related to the biology.

What does that mean for reopening businesses? For example, restaurants or movie theatres may try to make the environment safer by having fewer tables or selling fewer seats. Will that work, if people are still spending
2 hours together?

For every extra body you take out of a room, you are lowering the risk that somebody infected is in there to start off with. Then assuming that someone in that environment is infected, there is a gradient of respiratory droplets from that person that radiates out. So, certainly, having people spread out more in enclosed environments is an important way to reduce infection, but it’s not the solution to controlling all infections. Having a restaurant at half capacity that is still enclosed and has no or very little air exchange is going to be just as risky, but to fewer people.

For the medical community, fall is the start of the medical conference season. People who plan to attend these conferences are thinking about flying. You wrote a blog recently on Flying in the Age of COVID-19. We’ve heard stories of people taking off their masks once they are on board. Is flying too risky?

The cabin of a plane is almost as good as you can get for an indoor environment. Your biggest risk on the flight is not the person in front or behind you, it’s the person beside you that you strike up a conversation with. That’s a face-to-face conversation from very close, so in a very short period of time, infection can occur. Just understanding where the risks are and behaving appropriately is important if you are going to fly. Your risks are those people immediately around you and surfaces you touch, going to bathrooms, things like that.
With regard to masks on flights, the longer the mask can stay on the lower the respiratory emissions from that person. Taking a mask off for short periods of time to eat or drink does increase the risk, but if the mask is worn the rest of the time, this balances out.
What frustrates me is that the mask is not really for you, it’s for everyone who is around you. They’re protecting you and you’re protecting them — it’s a bit of a social contract that you have when you are flying. If airlines are requiring you to wear masks, they shouldn’t be removed. People should understand that if you are going to fly — to get into these close-quartered spaces, we need to reduce harm as much as we can, and do our part.
If you are flying from places that have a high prevalence of infection and going to a place where hundreds of people will be gathering in the same space, you may just be tempting fate. Not only do you run the risk of becoming infected from the flight itself and all the associated activities — departure, arrival, baggage claim, transportation, etc —  but you are going to be sitting in an environment with colleagues for hours on end.
And if you are infected 1 to 3 days after your flight, then we have a much larger problem. It’s no longer just you. It’s everyone you are there with. So these things need a lot of thought before we embark on this type of event again.

In one of your blogs you advocate dropping the term “social distancing.” Why is that?

Along with many epidemiologists, I’ve been trying to change the term from social distancing to physical distancing. It’s a small change but it makes a big difference. It’s not about being disconnected socially from the people around you — it’s creating a physical space between people that is almost too far for the virus to be transmitted. That’s the basis of the 6 feet. The vast majority of respiratory emissions will drop and land at the feet of someone 6 feet away, whereas many will hit their face and chest of a person only 3 feet away.
Creating physical distance — not becoming socially isolated — is the goal of these mitigation strategies. If I’m standing 10 feet from somebody across my lawn, I’m having social interaction but I still have the physical distance I need to be safe. The closer you are, the more dangerous it is.

What are the biggest misunderstandings right now driving people’s behavior when outside of the home?

Masks are a big misunderstanding at the moment. Because we have this idea that masks were made to protect the wearer, people have had a hard time adopting the idea that masks are an important part of the control of infection when you can’t physically distance. And the narrative that got mixed up from the CDC in the effort to try to protect PPE for healthcare workers only added to the confusion that we have now in society. When you add politics on top of that, it’s become a silly debate when we know it has an effect. That’s disappointing to me.
The CDC has done it again with changing fomites from being a risk to not being a risk in a period of a week and a half. Data doesn’t change that quickly, but we were all scratching our heads about why they lowered the risk of fomite transmission. We knew it wasn’t the primary driver but it was there. They put it in the same category as cats and dogs, and that just confused everyone in public health. Where’s the data that helped make that decision?
Now they’ve moved it back, saying they didn’t mean to add to the confusion. But now we’ve had a week of dialogue where surfaces aren’t as important.
Because this is so new [to the USA] and we don’t have a history of widespread epidemics of infectious diseases in recent memory, we don’t really know how to react and behave correctly as a society yet. Other countries that are scarred by their history, like Hong Kong and Taiwan, were able to jump straight into it and get control very quickly because the general population already knew the behaviors they needed to do in order to limit the spread of the virus.

We are the infants in all this. We are still learning and that’s been hard. People need to understand that masks have a role, and surfaces have a role, and that all the things that we’ve been discussing — enclosed spaces, long time, etc, all have their part in controlling the trajectory of what happens over the next few weeks, months, or year — whatever we are dealing with now.

What mistakes are we making in our early efforts to open up?

My biggest fear is opening without a plan. If you read my blogs, it’s all about planning. Give people the tools they need to make the best decisions/choices for themselves and their families in the risks they face and the ways they can reduce them.
I’m finding that a certain group of people are rushing to open and maybe haven’t thought it through enough. I’m fortunate to work with people who are really thinking about how to reopen and do it as safely as they possible can. Even though they were given the green light to open last week, they chose not to until they had systems in place to protect not only their workers but their guests.
Erin S. Bromage, PhD, is an associate professor of biology at the University of Massachusetts Dartmouth, where he teaches courses in immunology and infectious disease. Dr Bromage’s research focuses on the evolution of the immune system, the immunological mechanisms responsible for protection from infectious disease, and the design and use of vaccines to control infectious disease in animals. He also focuses on designing diagnostic tools to detect biological and chemical threats in the environment in real-time.
https://www.medscape.com/viewarticle/931594#vp_1

Feds expect coronavirus to drain trillions from US economy

The feds expect the coronavirus crisis to drain trillions of dollars from the US economy over the next decade, in the latest sign of the pandemic’s economic devastation.
The crisis will lead to a $15.7 trillion reduction in the nation’s gross domestic product — the value of all goods and services produced here — from this year to 2030 without adjusting for inflation, the Congressional Budget Office said Monday.
The nonpartisan agency expects a plunge of $7.9 trillion when adjusting for inflation, or 3 percent of the cumulative real GDP the office projected for that 10-year period in January.
The CBO said social-distancing measures aimed at controlling the deadly virus and the resulting business closures will likely reduce consumer spending, while a drop in energy prices is expected to curtail US investment in the industry.
Legislation aimed at blunting the economic impact of the virus will “partially mitigate the deterioration in economic conditions,” CBO director Phillip L. Swagel said. He added that the projections are uncertain because it’s unclear how the pandemic will develop going into next year and how it will affect the economy.
“Additionally, if future federal policies differ from those underlying CBO’s economic projections — for example, if lawmakers enact additional pandemic-related legislation — then economic outcomes will necessarily differ from those presented here,” Swagel wrote in a letter to Senate Minority Leader Charles Schumer (D-NY), who requested the analysis.
The nation’s GDP already suffered its worst contraction since the Great Recession in the first quarter of 2020 as the pandemic roiled the global economy. The CBO’s analysis also came ahead of the feds’ monthly employment report on Friday, which is expected to show unemployment at or near 20 percent in May.
Schumer and Sen. Bernie Sanders (I-Vt.) said the gloomy numbers underscore the need for Congress to pass another coronavirus stimulus bill. Lawmakers have already approved nearly $3 trillion in stimulus spending since late March, and they’ll be talking about another package “in the next month or so,” Senate Majority Leader Mitch McConnell (R-Ky.) said last week.
“In order to avoid the risk of another Great Depression, the Senate must act with a fierce sense of urgency to make sure that everyone in America has the income they need to feed their families and put a roof over their heads,” Schumer and Sanders said in a joint statement. “The American people cannot afford to wait another month for the Senate to pass legislation.”
https://nypost.com/2020/06/02/coronavirus-will-drain-trillions-from-us-economy-by-2030/

FDA extends action date for Novartis application for ofatumumab in MS

The FDA has notified Novartis (NYSE:NVS) that it needs more time to review its supplemental marketing application seeking approval to use Arzerra (ofatumumab) to treat patients with relapsing forms of multiple sclerosis (MS).

The new action date will be in September.

The CD20-directed cytolytic antibody is currently approved in the U.S. for chronic lymphocytic leukemia.

The company expects a regulatory nod in Europe by Q2 2021.

https://seekingalpha.com/news/3579832-fda-extends-action-date-for-novartis-application-for-ofatumumab-in-ms

Minneapolis Hospitals Brace for COVID-19 Surge Following Protests

Clinicians in Minneapolis are anxiously awaiting what the next few weeks will bring, given the large protests against systemic racism and police brutality that began not long after the state’s reopening, during which distancing and mask-wearing were often spotty.
The city is where a white police officer was captured on video May 25 kneeling on the neck of a black man, George Floyd, for nearly 9 minutes and killing him. Thousands of people have filled the streets in Minneapolis and other cities across the U.S. in protest.

“We are already on the verge in terms of staffing and space,” said Caitlin Eccles-Radtke, MD, an infectious disease physician at Hennepin County Medical Center in Minneapolis. “We are getting closer and closer to being overly full.”
Eccles-Radtke said hospitalists were already expecting things to pick up right around now, two weeks after the state’s stay-at-home orders were lifted on May 18. Her facility has already been “busy and stressful” and additional units have already been converted into COVID-19 ICUs.
“Knowing how this spreads and how many people have been out all hours on multiple days and nights, I’d be remiss to say nothing would happen,” she told MedPage Today. “The question is the increase in volume: will it be manageable? We are not sure yet but we are quite nervous.”
Reopening and the protests are occurring against a backdrop of a rising infection rate in the state, according to Ryan Demmer, PhD, MPH, an epidemiologist and community health expert at the University of Minnesota. The state has recently had about 600 to 1,000 new infections and about 30 deaths per day, he said.

Local models predicted a peak in early- to mid-June, Demmer said, but that was before the economy started reopening and before the protests occurred.
“Given what we know about this virus, at the top of the list of things you don’t want right now are large public gatherings,” Demmer told MedPage Today. “You have people from Minneapolis and other areas coming together with good potential for spread. Then they go back to their communities and perpetuate the spread further. That’s a real concern.”
Hospitals in Minneapolis haven’t exceeded surge capacity, Demmer said, given the time bought by stay-at-home orders that allowed them to convert regular beds to ICU beds.
Tim Sielaff, MD, PhD, chief medical officer of Allina Health, which operates Abbott Northwestern Hospital in Minneapolis, said in a statement that the hospital “hasn’t hit surge capacity so [it] won’t be making any other adjustments.”

“Allina Health has been actively preparing for a surge in COVID-19 patients for the last few months,” Sielaff said in the statement. “Our careful planning and preparation is not in response to the recent protests, but as part of our system-wide response to the COVID-19 pandemic.”
But Eccles-Radtke cautioned that ICUs in Minneapolis “are pretty full. There’s not a lot of extra capacity in the Twin Cities right now, which is why this is scary if things blow up.”
She noted that Minneapolis and St. Paul have been reporting hospital capacity so that paramedics can route patients appropriately, not overwhelming any single hospital.
Demmer agreed that “if things start to ramp up, there are scenarios projected where we could run out of space in the hospitals.”
Eccles-Radtke and her crisis response team have also asked city and state officials for modeling data to help predict what a resultant surge may look like, based on the number of people that were out at the protests, what percentage were wearing masks, and other factors.

Many protesters did appear to be wearing masks, Eccles-Radtke and Demmer said, and the fact that the protests were outdoors allowed participants to physically distance from each other.
Still, not all were wearing masks, Eccles-Radtke said, and there was “yelling, there was spit, aerosols, droplets. These people were in close proximity. It’s a big worry.”
The fact that the majority were younger and therefore at lower risk of being severely ill and dying from COVID-19 was a positive — but “younger people can be asymptomatic carriers,” she warned. “What happens in 2 or 3 weeks to mom or grandma, we don’t know.”
Demmer said people have a false sense of security because of the disease’s high rate of asymptomatic transmission. “You don’t know if you’ve come into contact with someone who’s infected…. If just one infected person shows up to the protest, it could become a super-spreader event.”

Infections among healthcare workers who attended the protests are also a concern, particularly among those who work at nursing homes, which have been hard-hit by COVID-19, Eccles-Radtke said.
She recommends that anyone who attends the protest should quarantine themselves for two weeks.
A spokesperson for the Minnesota Department of Public Health told MedPage Today that the state is developing plans to provide testing in both Minneapolis and St. Paul to people involved in the protests. The plans are still being formulated, so no other details are yet available, the spokesperson said.
Andrea Westby, MD, an expert in community health at the University of Minnesota, said she’s particularly concerned because many African Americans attended the protests and this group has been particularly hard-hit by the virus.
“I respect peoples’ rights to choose justice and accountability over COVID,” Westby said. “We need to do the best we can to minimize damage.”
https://www.medpagetoday.com/infectiousdisease/covid19/86829

Apple is tracking iPhones stolen by looters

Apple has an eerie message for the looters who have pillaged its stores during recent protests: We’re watching you.
Thieves who made off with iPhones from ransacked Apple retail locations in recent days quickly learned that the gadgets were loaded with special security software, as they displayed a message on their screens indicating that their locations were being monitored.
“Please return to Apple Walnut Street,” read the onscreen message of an iPhone stolen from an Apple store in Philadelphia, according to social media posts. “This device has been disabled and is being tracked. Local authorities will be alerted.”

Apple — which has recently been gearing up to reopen over 100 stores across the United States following an extended closure due to the coronavirus pandemic — saw locations attacked and looted in cities including New York, Los Angeles and Washington.
The looting sprang from a week of civil unrest and protests following the police killing of George Floyd, an event which Apple chief Tim Cook called “senseless” in a memo to employees over the weekend.
“I have heard from so many of you that you feel afraid — afraid in your communities, afraid in your daily lives, and, most cruelly of all, afraid in your own skin,” Cook said in the note, which was published by multiple news outlets.
“To our colleagues in the Black community — we see you,” he added. “You matter, your lives matter, and you are valued here at Apple.”
https://nypost.com/2020/06/02/apple-is-tracking-iphones-stolen-by-looters/

FDA approval tracker: several early decisions in May

Last month the FDA greenlit four oncology approvals early and the first GnRH antagonist in uterine fibroids.

The US FDA approved four therapies early last month, all in cancer indications. One was Deciphera’s Qinlock, approved three months early in gastrointestinal stromal tumours as a fourth line treatment. On the very same day Blueprint’s competing project Ayvakit received a complete response letter, as expected, in the wake of the failure of the pivotal Voyager study.
Qinlock’s real potential lies in earlier lines of therapy and a second-line study should readout next year. Ayvakit meanwhile looks like it will be limited to a niche group of patients with specific mutations, where it is already approved.
Another early win was Bristol Myers Squibb’s Opdivo/Yervoy/chemo triplet in front-line lung cancer. The approval was based on the Checkmate-9LA study, and came despite ongoing questions around what Yervoy brings to the regimen, given its known toxicities.
Earlier in the month Opdivo plus Yervoy was approved in ≥1% PD-L1 expressers; Merck & Co’s Keytruda can already be used as a monotherapy in these patients, and a Keytruda/chemo combo is approved in all-comers.
Lastly, two targeted therapies were greenlit early, Eli Lilly’s Ret inhibitor Retevmo and Novartis’s Met inhibitor Tabrecta, however both come with safety warnings.
Retevmo, which Lilly gained through its Loxo acquisition, was approved in advanced Ret-driven lung and thyroid cancers. The label includes warnings about QTc prolongation, hypersensitivity, and haemorrhagic events; analysts have noted that these toxicities have not been reported with Blueprint’s rival Ret inhibitor, pralsetinib.
Pralsetinib is due to hear on US approval in lung cancer in November, and Blueprint plans to file in thyroid cancer this month.
Novartis’s Tabrecta meanwhile was greenlit early for metastatic NSCLC with Met exon 14 skipping. The label includes a precaution about interstitial lung disease /pneumonitis, which occurred in 4.5% of patients in the phase II Geometry mono-1 study, with 1.8% experiencing Grade 3 side effects.

Notable first-time US approval decisions in May
Project	Company	2026e sales ($m)	Outcome
Qinlock (ripretinib)	Deciphera	1,311	Approved (early 3 months)
Retevmo (selpercatinib)	Eli Lilly	1,172	Approved (early ~2 months)
Ayvakit	Blueprint Medicines	918	CRL
Phexxi (Amphora vaginal pH regulator)	Evofem biosciences	541	Approved
Oriahnn (Orilissa/elagolix)	Abbvie/Neurocrine	510	Approved
Tabrecta (capmatinib)	Novartis	355	Approved (early ~2 months)
Kynmobi (apomorphine sublingual film/APL-130277)	Sunovion/Aquestive Therapeutics	189	Approved
Dasotraline/SEP-225289	Sumitomo Dainippon Pharma	119	NDA withdrawn
Zilxi (FMX103/minocycline)	Menlo Therapeutics	112	Approved
Intravenous artesunate	Amivas	–	Approved
Cerianna (fluoroestradiol F 18)	Petnet Solutions/Zionexa	–	Approved
Tauvid (flortaucipir F 18)	Eli Lilly/Avid Radiopharmaceuticals	–	Approved
Sources: EvaluatePharma, Go or no go? Oncology dominates upcoming decisions

Restrictions
Oncology aside, Abbvie’s Oriahnn became the first approved GnRH receptor antagonist for uterine fibroids at the end of May. However, strict language surrounding contraindications could potentially limit Oriahnn’s use, and indeed other projects in the GnRH class, according to SVBLeerink analysts.
Those advised against using the drug include women with an increased risk of blood clots, and those over 35 who smoke or have uncontrolled hypertension.
Oriahnn’s label discloses two thrombotic events in the phase III program that were not discussed previously; one thrombosis in the calf and a pulmonary embolism. It is probable that these events were caused by the hormone add-back therapy (ABT) needed to counteract the menopause-like symptoms associated with GnRH inhibition.
ABT carries its own risks and is not advised in patients with high BMI, diabetes and cardiovascular disease. Nonetheless, a contraindication in smokers for Oriahnn was not expected by analysts.
No thromboembolic signals have been disclosed from competitors Myovant or Obseva to date. Myovant’s relugolix in combination with ABT was filed in uterine fibroids this week, while Obseva is also developing a low dose version of its antagonist linzagolix without ABT.
Obseva hopes that excluding ABT will open up linzagolix as a first-line treatment, although the project has safety issues of its own in terms of bone mineral density loss.

Supplementary and other notable approval decisions in May
Product	Company	Indication (clinical trial)	Outcome
Alunbrig	Takeda	IL ALK positive NSCLC (Alta -1L)	Approved
Darzalex Faspro (subcutaneous Darzalex)	J&J	Multiple myeloma (Columba MMY3012)	Approved
Dupixent	Sanofi	Atopic dermatitis in children aged 6 to 11 years	Approved
Farxiga	Astrazeneca	Reduce the risk of CV death or the worsening of heart failure in adults with HFrEF with and without type 2 diabetes (Dapa-HF)	Approved
Icosapent ethyl capsules (generic Vascepa)q	Hikma	To reduce the risk of cardiovascular events among adults with elevated triglyceride levels	Approved
Lynparza	Astrazeneca	mCRPC and germline or somatic HRR mutations (Profound)	Approved
Lynparza + Avastin	Astrazeneca	Advanced ovarian cancer maintenance with Avastin (Paola-1)	Approved
Opdivo + Yervoy	Bristol Myers Squibb	1L NSCLC without chemo (Checkmate-227)	Approved
Opdivo + Yervoy + chemo	Bristol Myers Squibb	1L NSCLC (Checkmate-9LA)	Approved (early 3 months)
Pomalyst	Bristol Myers Squibb	Adult patients with AIDS-related Kaposi sarcoma	Approved
Rubraca	Clovis	BRCA1/2-mutant recurrent mCRPC (Triton2)	Approved
Tecentriq	Roche	Monotherapy 1L NSCLC with high PD-L1  expression (Impower110)	Approved
Tecentriq + Avastin	Roche	Unresectable or metastatic hepatocellular carcinoma who have not received prior systemic therapy (IMbrave150)	Approved
Vesicare LS	Astellas	Neurogenic detrusor overactivity in paediatric patients	Approved
Sources: EvaluatePharma, Go or no go? Oncology dominates upcoming decisions

https://www.evaluate.com/vantage/articles/news/us-fda-approval-tracker-several-early-decisions-may