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Friday, September 23, 2022

Women With Type 2 Diabetes Die Sooner Than Men, Study Suggests

 Certain groups of people may face higher risks of early mortality and loss of life expectancy years from type 2 diabetes, a real-world population study showed.

In an English cohort, a few specific factors were associated with significantly higher odds of diabetes-related mortality, including:

  • Smoking vs not smoking: OR 2.01 (95% CI 1.71-2.36)
  • Age at diagnosis <65 years vs ≥65 years: OR 1.56 (95% CI 1.40-1.74)
  • Duration with type 2 diabetes over 10 years vs under 10 years: OR 1.21 (95% CI 1.09-1.34)
  • Women vs men: OR 1.11 (95% CI 1.00-1.23)
  • Living in a deprived area vs not: OR 1.28 (95% CI 1.14-1.42)
While having type 2 diabetes shortens life expectancy compared with the general population, this study showed that women were particularly affected (5.3 years shorter vs 4.5 years for men), reported Adrian Heald, MD, of Salford Royal Hospital in England, during a presentation at the European Association for the Study of Diabetes (EASD) meeting.

"We all know that type 2 diabetes shortens life," Heald said during a press conference. "Perhaps less so, thanks to the greater innovations in diabetes treatments, with cardiovascular reductions associated with those treatments."

"The key message [here] ... is that for women with type 2 diabetes, their lives are shortened more than men and their likelihood of dying is higher than men," he noted.

"Why this is happening is difficult [to understand]," he said, suggesting that it could be due to lipid handling, specifically with how LDL receptors behave.

"It may be that women are not having access to some medications," Heald added. "We interestingly found that women are taking less of the new drugs -- the SGLT2 inhibitors -- than men do. It may also be due to concordance, too -- the degree to which women actually take their medication as opposed to men."

"We don't know why, but we do feel this is a really important finding that's of interest ... something that requires more exploration in our cohort study and in others," he noted.

In addition to sex, those diagnosed prior to age 65 saw an average 8.2 years lost versus 1.8 years for those diagnosed later in life. Those who had diabetes for less than a decade saw 4.0 fewer years of life expectancy versus 4.9 years for those with a diabetes duration over 10 years.

Smoking was the most important factor that shortened lifespan for people with type 2 diabetes, with 10.2 years shaved off of life expectancy versus 2.7 years for non-smokers and 3.4 years for past smokers.

"The message is really clear: smoking is really bad for you if you have diabetes," Heald stressed.

For this analysis, Heald's group looked at data from 2010 to 2020 on people diagnosed with type 2 diabetes living in the Salford region of England. Actual death rates were compared with annual expected deaths calculated from the Office of National Statistics mortality rate.

A total of 11,335 individuals were included in the final analysis, including 5,540 new diabetes diagnoses and 3,921 deaths. Average age at type 2 diabetes diagnosis was 57.8, and average age at death was 78. The age-standardized mortality ratio was 1.84.


Disclosures

Type 1 Diabetes Outcomes Particularly Bad for Girls

 Girls may face a higher rate of type 1 diabetes-related complications and poor outcomes versus boys, according to a systematic review.

Across 86 observational studies focused on sex differences in pediatric patients with type 1 diabetes, all studies that compared HbA1c at the time of diagnosis found female patients had higher HbA1c levels than males, reported Silvia de Vries, MSc, an MD/PhD candidate at Amsterdam University Medical Center in the Netherlands.

This difference persisted throughout treatment, as 20 studies found girls continued to have higher HbA1c levels than boys versus only one study that favored girls, de Vries pointed out during a presentation at the European Association for the Study of Diabetes (EASD) meeting.

The meta-analysis showed that girls required higher insulin doses than boys in the total population, in select age groups, and when just looking at the first few days after initial diagnosis. Female patients required both higher basal insulin doses and total insulin doses, the researchers found.

On the other hand, much of the literature suggested that insulin pump therapy or continuous subcutaneous insulin infusions were far more commonly used among girls with type 1 diabetes than boys.

"We think that there may be several mechanisms at play," de Vries said during a press conference. "There may be a biological influence, especially in puberty -- hormones may influence insulin sensitivity." She added that both body composition and fat distribution may be additional biological factors playing into these sex differences.

"We also think that psychological causes are very important," she continued. "Boy and girls differ in disease-related attitudes and behaviors. We already know, for example, that quality of life scores are lower in girls without diabetes, as well. But this may very well interfere with treatment of type 1 diabetes."

Boys may also have higher levels of physical activity and different eating patterns that may play into these sex differences, de Vries suggested.

Her group found that when it came to complications of diabetes, female patients faced worse outcomes for the most part: while they tended to have less hypoglycemia, they had overwhelmingly higher rates of diabetic ketoacidosis (DKA), including at diagnosis, severe DKA, and DKA throughout treatment.

Girls not only saw more hospital admissions for DKA throughout the studies included, but saw a higher rate of hospital admissions in general, along with longer length of stays. Compared with boys, they also faced more vascular complications, including nephropathy.

As for quality of life, all 15 studies (nine in adolescents alone) assessing this outcome favored male patients. Not only did female patients see poorer overall quality of life, but they also saw more diabetes-related distress and greater fear of hypoglycemia.

"We strongly believe that identification of these differences is a very important first step," de Vries said.

Nevertheless, "we cannot exclude the influence of the treatment team and caregiver approach," she pointed out. "We do know that in adult females with type 1 diabetes that there still seems to be a treatment bias."

When comparing the clinical profile of patients with type 1 diabetes, the literature indicated that female patients tended to have a longer duration of diabetes symptoms, have a higher BMI (in adolescence and at all ages), and have a higher prevalence of overweight and obesity.

In contrast, male patients had a higher prevalence of underweight, as well as weight loss before type 1 diabetes diagnosis. Boys also tended to had more favorable diastolic blood pressure and lipid profiles.

The present meta-analysis thus joins other reports of sex differences in diabetes patients. In another study presented at EASD 2022, researchers found adult women with type 2 diabetes had a significantly shorter life expectancy than men with the condition.

Both type 1 and type 2 diabetes are steadily rising in prevalence among American children and teenagers.


Disclosures

De Vries and co-authors reported no disclosures.

Secura PI3K Inhibitor Fails to Pass Muster With FDA Advisory Committee

 The FDA's Oncologic Drugs Advisory Committee (ODAC) made a clean sweep of its 2-day meeting, deciding that the PI3K inhibitor duvelisib (Copiktra) does not offer a favorable risk-benefit ratio for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

By an 8-4 vote, the panel came down on the side of the FDA staff perspective that duvelisib had a potentially detrimental effect on survival in a randomized trial that supported Secura Bio's approval application. Analysis of 5-year overall survival (OS) from the randomized DUO trial showed a hazard ratio of 1.09 versus the ofatumumab (Arzerra) control arm in an intention-to-treat analysis and 1.06 in the indicated population (relapsed/refractory disease and two or more prior lines of therapy).

Adjusted analyses yielded similar results. Although not statistically significant, the suggestion of a survival detriment, along with evidence of high rates of toxicity, swayed the panel's overall opinion.

The duvelisib outcome followed negative votes for the risk-benefit profile of the lung cancer drug candidate poziotinib and the myeloma treatment melphalan flufenamide (Pepaxto) during the first day of the meeting.

'Playing With Fire'

The outcome continued a string of bad news for the PI3K inhibitor drug class. At a meeting in April, the ODAC panel reviewed data showing a consistent trend toward an adverse impact on OS across the entire class, which an FDA report characterized as "unprecedented in the field of oncology."

"I think with this drug and with this class of drugs, we are playing with fire," said Mikkael Sekeres, MD, of the University of Miami's Sylvester Comprehensive Cancer Center, following the duvelisib vote. "This drug had modest activity with significant toxicity, as did other members of this class, and was compared to a drug that we would no longer use in this setting. This drug [duvelisib] itself we would no longer use in this setting, as patients received other drugs, such as BTK [Bruton's tyrosine kinase] inhibitors and BCL-2 inhibitors, for which they would have been disqualified from the study."

"So, we're left with a drug that has substantial toxicities and a questionable indication today," he added.

Other ODAC members struggled with the data and with their decision, even when they voted no.

"If you have an indolent disease, and overall survival obviously is very difficult to figure out in that setting, then you become more compelled by the overall response rate and progression-free survival," said Christopher Lieu, MD, of the University of Colorado Cancer Center in Aurora. "The progression-free survival benefit here is compelling ... and we want more drugs in this setting."

"If you have a disease where survival is measured in weeks to months, the bar you set for toxicity and what you're expecting out of the therapy is pretty low," he added. "But the flip side is also true. If you have an indolent disease, what is the cost to our patients that we're going to expect out of a therapy in a setting where we're not sure that it improves overall survival?"

Same Data, Different Perspectives

Similar to Thursday's session on poziotinib, the FDA staff and the sponsor, Secura Bio, had sharply differing views on duvelisib's risks and benefits. Noting that an updated survival analysis from the DUO trial showed a trend favoring the control arm, the FDA staff report concluded that the "current benefit-risk of duvelisib in patients with relapsed or refractory CLL or SLL is not favorable."

Looking at the same data, Secura Bio representatives said the final survival analysis "does not support the conclusion of a detriment in OS in patients treated with duvelisib and did not identify any new safety concerns." They pointed to a huge imbalance in crossover treatment: 90 from the ofatumumab control arm to duvelisib versus nine from duvelisib to ofatumumab.

The FDA staff countered with adjusted analyses that accounted for the crossover disparity and still showed a trend toward excess mortality in the duvelisib arm. They also noted that several patients died of treatment-related adverse events after switching from ofatumumab to duvelisib.

A number of other factors confounded data assessment. Only 14% of the study population came from the U.S., and Black patients accounted for only 1% of the total, raising questions about the applicability of the findings. Ofatumumab is not widely available nor routinely used in the management of CLL/SLL.

The randomized trial excluded patients previously treated with BTK inhibitors, and BCL-2 inhibitors were not yet available. Those two classes currently represent first- and second-line treatment for CLL/SLL. Whether duvelisib, or any PI3K inhibitor, offers a benefit after progression on those two drug classes is unknown.

Several ODAC panelists expressed confusion and frustration with the data on survival and toxicity. Panelist David Harrington, PhD, a biostatistician at Dana-Farber Cancer Institute in Boston, offered a bottom-line assessment of the data.

"It is incumbent upon the sponsor to establish that there was a favorable risk-benefit profile," he said. "Given the current context -- the data about this class, extended follow-up on this study -- I don't think they've done that."

Rocky History

Approved 4 years ago, duvelisib was hailed as "an important addition to the evolving treatment paradigm for patients with CLL/SLL and follicular lymphoma (FL)." In the phase III, multicenter, randomized DUO trial of CLL/SLL, patients who received the PI3K inhibitor had a 7-month improvement in median progression-free survival (PFS) versus ofatumumab and a two-fold improvement in objective response rate.

Duvelisib had more toxicity versus ofatumumab, but appeared to be less toxic than idelalisib (Zydelig), the first approved drug in the PI3K inhibitor class. OS data, a secondary endpoint in DUO, were immature at the time of the approval.

The FL approval was based on the phase II single-arm DYNAMO trial, which showed a 43% response rate in rituximab (Rituxan)-refractory patients. The accelerated approval came with the stipulation that the sponsor (at the time, Verastem) would conduct a confirmatory trial.

Late last year, Secura Bio voluntarily withdrew duvelisib's FL indication, citing the "current treatment landscape for FL patients in the U.S. and the logistics, cost and timing of the post-marketing requirements."

At the April meeting, ODAC put the entire PI3K inhibitor class on notice about safety concerns, as data reviewed by the committee showed an excess of fatal events, as well as high rates of severe and overall toxicity in patients with indolent lymphomas, normally associated with a prolonged clinical course and survival. The panel agreed that future approvals for PI3K inhibitors should be contingent on survival data.

"Certainly, PFS, at least for most of us who voted yes, didn't appear to be a reasonable endpoint for this class of agents," ODAC chair Jorge Garcia, MD, of Case Western Reserve University in Cleveland, said at the time.

Then, in late June, the FDA singled out duvelisib in a warning about an increased mortality risk among patients treated with the drug in the DUO trial. FDA also announced plans for an ODAC meeting in September to discuss the updated OS data from DUO.

Prior to the duvelisib vote, Garcia said, "It has been obviously a complex discussion, and I predict that it's not going to be an easy vote."

https://www.medpagetoday.com/hematologyoncology/lymphoma/100904

Preclinical gene editing biotech Prime Medicine files for estimated $200 m IPO

 Prime Medicine, a preclinical biotech developing novel gene editing therapies for various diseases, filed on Friday with the SEC to raise up to an estimated $200 million in an initial public offering.


The company is developing one-time curative genetic therapies, and currently has 18 preclinical programs targeting areas such as sickle cell disease, various liver diseases, non-syndromic hearing loss, neuro-muscular conditions, Duchenne muscular dystrophy, and cystic fibrosis. Prime Medicine has established preclinical proof-of-concept in vivo with long term engraftment of edited human cells in mice targeting sickle cell disease.

The Cambridge, MA-based company was founded in 2019 and plans to list on the Nasdaq under the symbol PRME. Prime Medicine filed confidentially on December 20, 2021. J.P. Morgan, Goldman Sachs, Morgan Stanley, and Jefferies are the joint bookrunners on the deal. No pricing terms were disclosed.

Push to double up on Covid booster and flu shot may have a downside

 As the promotional push to get people vaccinated with one of the updated, bivalent Covid vaccines heats up, federal health authorities are urging Americans to consider getting their Covid shot and their flu shot at the same time. And with concern about a fall wave of Covid paramount in this effort, the messaging is stressing the importance of doing this sooner rather than later.

Earlier this week, Anthony Fauci, President Biden’s chief medical adviser, put it bluntly: “Get your updated Covid-19 shot as soon as you are eligible.” For many people over the age of 12, that would be right now.

There’s just one problem with the advice. It’s still early to get a flu shot.

The protection generated by influenza vaccines erodes pretty quickly over the course of a flu season. A vaccine dose given in early September may offer limited protection if the flu season doesn’t peak until February or even March, as it did during the unusually late 2021-2022 season.

“If you start now, I am not a big fan of it,” Florian Krammer, an influenza expert at Mount Sinai School of Medicine in New York, told STAT. “I understand why this is promoted, but from an immunological point of view it doesn’t make much sense.”

A number of studies have shown that the benefit of a flu shot wanes substantially over the course of a flu season — exacerbating effectiveness problems that are frequently seen when some of the strains in the vaccine aren’t well matched to the strains making people sick.

Work done by researchers from the Kaiser Permanente Vaccine Study Center and the Harvard School of Public Health estimated vaccine effectiveness declined by about 18% for every 28-day period after vaccination. A study done by scientists at the Centers for Disease Control and Prevention and elsewhere showed that the vaccine’s protection against flu that is severe enough to trigger hospitalization decreases by between 8% and 9% per month after vaccination. In older adults, who are more likely to get seriously ill from flu, the decline happened at a rate of about 10% to 11% per month.

“You’ve got about four months of pretty solid protection,” said Emily Martin, an associate professor of epidemiology who specializes in flu at the University of Michigan School of Public Health. Martin was an author on the latter study.

If you ask someone who researches flu and flu vaccines, they will likely quietly — or in some cases, not so quietly — advise you to wait at least until the end of October to get a flu shot, though they’ll attach the caveat that if you start to hear about flu activity picking up where you live, you should fast-forward your plans.

“I’ll follow very carefully the activity in the community,” said Michael Osterholm, director of the University of Minnesota’s Center for Infectious Disease Research and Policy. “If it starts to pick up, I’ll move immediately. Otherwise I’m counting on sometime in late October, early November.”

Martin gets her flu shot every October two weeks before a scientific meeting she attends, unless she hears something that makes her rethink that timing. “I’m right across the street from a dorm,” she said. “As soon as I start seeing those flu numbers go up, I’ll go get it.”

Krammer waits longer. “I usually get the flu shot at the end of November, because typically we see a rise in cases in the middle of December, and by then my antibody response should have kicked in, and be at its prime for a December-January season, and there might still be enough for a late season,” he said.

The CDC’s official advice states that “September and October are generally good times to be vaccinated against flu,” though the agency’s website adds that “ideally, everyone should be vaccinated by the end of October.”

The “everyone” thing is one of the sticking points when trying to time flu vaccinations. While waiting would generally make more sense on an individual basis, the goal most years is to get flu shots into tens of millions of arms over a period of a few weeks. That’s a big task for the health care system when it’s just flu, but this fall, vaccine deliverers are trying to get Covid boosters and flu shots into as many arms as possible.

Noel Brewer, a professor of health behavior at the University of North Carolina, said he thinks moving to this joint-administration approach is the right idea. Covid vaccine delivery has been overly complicated, he said, requiring people to keep track of too many things. How many shots they’ve had. When they last had a shot. When they are next eligible for a shot.

People have been tuning out, he said — an assertion bolstered by the booster uptake rate. The percentage of eligible people who got a second Covid booster is lower than the percentage of people who got a first booster, which is lower than the percentage of people who got a primary series of two shots.

Making things simple and pairing Covid shots with another health intervention makes it easier for people, Brewer said — even if the combination benefits one of the interventions more than the other.

“I don’t think any of this is free. I don’t think any of it’s easy,” he said. “There isn’t a single best option that we can do that doesn’t have some consequences. We just have to take the less onerous consequence.”

Ed Belongia, director of the Center for Clinical Epidemiology and Population Health at Wisconsin’s Marshfield Clinic Research Institute, said in a case like this, public health authorities need to think in terms of what works best for the collective, not each individual in it.

Some people get flu shots every year; they are motivated to take advantage of this preventive tool. Some of them may well decide to book a flu shot appointment for later in the fall rather than get their flu shot when they get a Covid booster. Belongia is among them. He’d rather wait a while and he’s planning on getting a high-dose flu shot, which will probably have more side effects than the standard vaccine. While getting flu and Covid shots during the same health care visit is safe, Covid shots can carry quite a kick. Belongia would prefer to get the two vaccines separately.

But other people are unlikely to book two health appointments to get two different shots, authorities realize from experience with other health interventions. Given that reality, what’s ideal may have to give way to what’s pragmatic.

“There’s a tradeoff, right, between starting too early and having waning, versus missing opportunities to vaccinate,” said Belongia. “In terms of trying to optimize timing, you lose people who don’t get vaccinated at all. Trying to balance those is difficult because you don’t know when the flu season is going to begin each year.”

That is the other key sticking point with advising people on when to get a flu shot. Ideally, getting vaccinated shortly before flu season starts to take off would make sense. Estimating when flu season is going to take off — well, good luck with that.

“Trying to predict flu seasons is in many cases a lot harder than predicting the stock market,” Osterholm said.

Influenza is notoriously variable. In many years, activity only really comes to a head in January and February, but in 2021-2022, the week of peak activity was the week between Christmas and New Year’s. That said, there was a long tail to the 2021-2022 season, with cases remaining at atypical levels in June.

Figuring out what flu is going to do — when it’s going to hit, which subtype will be dominant, whether the season will be tough or mild — is even harder in the pandemic era. Covid wiped a lot of pathogens off the table for a time. There was no flu season to speak of in 2020-2021, and while the 2021-2022 season was unusually extended, it was mild.

Some of the bugs that stopped circulating in the early part of the pandemic have come back with a vengeance, and scientists worry that the same will be true when flu activity returns to pre-pandemic levels. In a recent interview with Bloomberg News, Fauci warned the country might be facing a “pretty bad flu season.”

Flu experts think that’s possible, but not guaranteed.

“If I had to predict, I do think, whether this year or in future years, sooner or later the immunity debt is going to catch up with us, particularly younger folks,” Martin said. “You’ve got entire birth cohorts of children growing into the population that haven’t had that regular introduction to viruses that they normally would have had between the years 0 and 3.”

Little kids play a pivotal role in spreading flu around communities. “They’re little bioreactors, right?” said Krammer.

People often look to the southern hemisphere to try to predict the coming winter’s flu activity, though what happens north of the equator doesn’t alway match what happened south of it.

This year Australia had a very active flu season, akin to pre-pandemic seasons, Kanta Subbarao, director of the World Health Organization’s Collaborating Center for Reference and Research on Influenza in Melbourne, Australia, said via email. Though most of the activity was caused by the influenza A virus H3N2 — a virus that is typically very hard on older adults — children were most affected this year, Subbarao said.

Elsewhere in the southern hemisphere, the flu season was not particularly active, said Osterholm, who suggested it’s not yet clear what we’re facing, influenza-wise.

“All I can do is say based on a typical year, 1) you don’t want to get the vaccine too early and 2) we could see everything from a mild to a severe flu season and everything in between and we don’t know,” he said. “And the best way to be prepared for that is to try to time your vaccination to what a typical winter season incidence looks like. And that means to me, mid-October to early November, and of course, always being open to change if we see unusual early activity.”

https://www.statnews.com/2022/09/09/doubling-up-on-covid-booster-flu-shot-may-have-downside/

Shakeup with Optum’s health data licensing sparks scientist outcry

 move by Optum to change longstanding practices for licensing data to academic institutions has sparked an outcry among researchers, who argue the move will make accessing data so costly and difficult that universities will scale back their research programs.

Optum notified users that future projects must access insurance claims data through an enclave hosted by another unit of the company. Optum is the data and pharmacy benefits arm of the insurance giant UnitedHealth Group.

But using the enclave results in higher costs and technical complications that may make it harder to harness the data for artificial intelligence studies and other types of research. Some researchers also worried that Optum’s review of projects prior to granting data access may restrict the types of studies allowed to proceed.  Because of the higher costs, the University of Michigan is already telling faculty that it will have to limit use of the Optum data, according to an email obtained by STAT.

“We will not be able to financially support the continuation of projects beyond our current license,” the email said. It added that researchers who want to use the Optum data going forward will need grant funding to pay the licensing fees, which typically cost tens of thousands of dollars per project.

The concerns over data access underscore broader tensions surrounding the use of huge collections of health information controlled by commercial entities. Optum has one of the largest troves of health data, spanning insurance and pharmacy claims, as well as clinical information such as patients’ diagnoses, treatments, and lab results. The data repository used by academic institutions contains details on the care of about 270 million Americans.

Federal rules allow that information to be licensed to a broad array of parties as long as it is de-identified and cannot be linked to an individual. Because companies like Optum can compile the data from a wide range of sources, they are an important supplier for researchers who could not otherwise get access to the same breadth of information. Optum’s data is licensed by many large universities across the country, including Stanford and the University of Texas.

“Optum has been evolving its data access models to meet the changing needs for real world data access, data security, privacy and utilization,” a spokesperson told STAT. The spokesperson said the company is working closely with its academic customers “to help ensure current research is not disrupted.”

As the holder of the data, Optum and its parent, UnitedHealth Group, are free to decide which parties they wish to license data to and under what conditions, which may not always match with societal interests in academic freedom and transparency.

In 2019, UnitedHealth Group pulled out of a data collaboration with the Health Care Cost Institute, which uses data from several commercial insurers to support research into the drivers of health care use and spending in the United States. Other insurers such as Aetna, Humana and Kaiser Permanente continued to contribute data.

The academic institutions affected by Optum’s decision to change its data licensing arrangements reflect a small fraction of the company’s business. It also does business with a much larger universe of health care providers, insurers and life sciences companies.

The move does not affect existing licenses, and some institutions are negotiating extensions to support publication of ongoing research. The email from the University of Michigan indicated that new projects cannot be started after the current license ends in February and that research not supported by grants will be unable to access the new data portal.

“This is unfortunate given that OptumInsight has been a partner of ours for nearly 8 years, and their data have provided many valuable insights,” the email said.

https://www.statnews.com/2022/09/23/optum-health-data-licensing-research/

Pfizer Resumes Dosing In Phase 3 Hemophilia Gene Therapy Trial 6 Months After FDA Lifts Hold

 

  • Pfizer Inc 
    PFE
     and its partner Sangamo Therapeutics Inc  have reopened enrollment in phase 3 AFFINE study hemophilia A gene therapy trial. 
  • Trial sites will begin to resume enrollment this month, with dosing expected to restart in October.
  • The study will evaluate the efficacy and safety of a single infusion of giroctocogene fitelparvovec in more than 60 adult male participants with moderately severe to severe hemophilia A. 
  • The primary endpoint is the impact on annualized bleeding rate (ABR) through 15 months following the treatment.
  • The FDA put the study of giroctocogene fitelparvovec on hold in November 2021. Pfizer hit pause after seeing some patients experience blood clotting protein factor VIII activity greater than 150%. 
  • In March this year, the FDA lifted the clinical hold, but Pfizer kept the voluntary pause in place while working to meet "all necessary conditions," including approval of updated trial protocols by regulatory authorities. 
  • In May, Sangamo said the trial would start in Q3 of 2022, with data expected in 2H of 2023. The target for the data drop is further delayed to the first half of 2024.