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Thursday, February 3, 2022

In young people, women are 44% more likely than men to have strokes

 University of Colorado School of Medicine faculty members Michelle Leppert, MD, and Sharon Poisson, MD, had a hunch that younger people were having strokes at a higher rate than most health care professionals realized, but when they dug into the numbers, the findings even surprised them: In adults 35 and younger, women are 44% more likely than men to suffer ischemic strokes — strokes caused by blood clots that travel to the brain.

Though the researchers — both in the Department of  Neurology — looked just at occurrences, not causes, in their study, they do note that “more research is needed to better define the etiological sex differences of ischemic stroke in young adults and the contributions that nontraditional risk factors, such as pregnancy, postpartum, and hormonal contraceptives, play in the overall burden of ischemic strokes in young women.”

We spoke with Poisson about the research, the team’s findings, and their next steps.

 

Q: Did you go into the research expecting this disparity between men and women? Or was this a surprise result?

A: It is a bit of a surprise when you put it in the context of past stroke literature. We have seen some hints of this in recent years — Dr. Leppert actually did one of the big administrative studies that was included in this paper where she found this difference — but it was one study. The question was, can we make a larger conclusion by combining more studies? We have seen hints that this may be the case, but this confirms that when you put lots of large data sets together, it seems to hold true.

 

Q: Did you look at the reasons women are at such higher risk? Or was this more about defining the problem?

A: We’d love to look at causes. This really just confirms that in the youngest age groups, that women had a higher incidence of stroke compared to men. It doesn’t tell us anything about why. That is the work that needs to be done. It’s hard to take anything from this study and make it actionable. It is kind of, “This is us understanding the problem so that we can now design studies to fix the problem.” It is important for us to remember that strokes happen in young people, strokes happen in young women. Recognizing that is really critical. Now that we understand better what the problem is, we can continue to work on solving it.

 

Q: What is the next step with this research?

A: The next step, now that we see that there is a difference in stroke incidence in young women versus young men, is to conduct a more detailed clinical study where we’re able to collect more detailed information about each of these strokes. To look at what led to the stroke so that we can better identify young adults who are at risk of stroke and do a better job of preventing those strokes. That’s the ultimate goal.

 

Q: Would that be using the same data you used for this study, or starting from scratch?

A: Administrative data sets are great because they include a lot of people, which makes it easier to study a less common disease, but they're limited in terms of what information is in there. We can’t collect all the information we want from those datasets. We could go about it by trying to link clinical data to some of these large datasets, but the other way to do it, which is more work in terms of time, is to collect prospective data on many young people with stroke. That’s something that would really need to be a big, multicenter study, because it’s a less common disease. It would be like a registry, where every time a young person comes in with a stroke, they are collecting that information. There are people out there who are trying to do this now, it’s just limited. We still have a long way to go.

 

Q: What is the biggest takeaway for young people from this study?

A: The number-one thing is understanding that stroke can happen at any age. Sometimes when young people have stroke-like symptoms, nobody thinks, “This could be a stroke.” They’ll try to sleep it off, and not recognize that, “This is an emergency, and I need to get to the emergency room so I can get treatment for a stroke.” Stroke can happen to anybody, and knowing the symptoms of stroke is really critical. We know things like high blood pressure, diabetes, smoking, and high cholesterol are risk factors for stroke and can contribute to stroke even in young people. Preventing those risk factors is really critical for everybody.

 

Q: What are stroke symptoms to be aware of?

A: We use the acronym “BE FAST”: The B is balance, E is eyes, F is face, A is arm, S is speech, and T is time. So sudden changes in balance, in vision, droopiness on one side of the face, sudden weakness on one side — if you put your arms up and one drifts down — or a sudden change in speech, either slurred speech or trouble getting the right words to come out. Those are the most common symptoms of stroke. The “T is time” is to remind us that time is brain. The sooner we treat strokes, the better people do. So calling 911 and getting to the ER are the most important things to do if somebody has sudden onset of those new symptoms.

 

Q: What is the treatment for stroke, if you do take someone to the ER?

A: We have a few different types of treatments. There’s a clot-busting medicine called TPA, which goes into the IV and breaks up blood clots. If there's a blood clot in the brain, it can help to break that blood clot up to try to save any of the brain that that hasn't had a stroke yet. In some strokes, when there’s a clot in a big artery inside the brain that we can see on a scan, our interventional neurosurgeons or neurologists can go pull the clot out from the inside of the artery.

 

 

Q: Can strokes be fatal?

 

A: Most ischemic strokes are not fatal (about 15% lead to death in the first 30 days), but they are the number-one cause of disability in adults in the United States. Most people survive their ischemic stroke, but often people will survive with disabilities, such as trouble speaking or trouble moving one side of the body. We know the sooner we treat people for stroke, the more likely we can stop the stroke in its tracks, and the more likely it is that somebody will return to normal or close to normal after the stroke.

Sanofi eyes rising earnings in 2022 after Q4 earnings increase

 

French drugmaker Sanofi said it would aim to further increase its earnings per share (EPS) this year as it reported rising fourth-quarter results on Friday.

The group, which is hoping for a comeback after losing ground in the COVID-19 jab race, is eyeing an increase in its EPS in the "low double-digit" in 2022.

Its sales in the three months to December grew 4.1% to 9.99 billion euros ($11.45 billion) while its EPS came in at 1.38 euros.

For the whole of 2021, its earnings per share rose by 15.5% at constant exchange rates, while the company had guided for a rise of 14%.

https://www.marketscreener.com/quote/stock/SANOFI-4698/news/France-s-Sanofi-eyes-rising-earnings-in-2022-after-Q4-earnings-increase-37742962/

SANOFI CFO SAYS STILL SEES Q1 FOR APPROVAL OF ITS COVID-19 VAX

 SANOFI CFO SAYS STILL SEES Q1 FOR APPROVAL OF ITS COVID-19 VACCINE

https://www.marketscreener.com/quote/stock/SANOFI-4698/news/SANOFI-CFO-SAYS-STILL-SEES-Q1-FOR-APPROVAL-OF-ITS-COVID-19-VACCI-8230-37742999/

Intellia to Acquire Rewrite Therapeutics

 Intellia Therapeutics (NASDAQ:NTLA), a leading clinical-stage genome editing company focused on developing curative therapeutics leveraging CRISPR-based technologies, today announced the acquisition of Rewrite Therapeutics, Inc. (Rewrite), a private biotechnology company focused on advancing novel DNA writing technologies.

Rewrite has developed promising new tools for genome editing, including DNA writing via CRISPR/Cas9-guided polymerases. Founded by pioneering scientists Shakked Halperin, Ph.D., and Professor David Schaffer, Ph.D., of the University of California, Berkeley and backed by Civilization Ventures and Prefix Capital, Rewrite’s DNA writing technology may enable a range of precise editing strategies. These strategies include targeted corrections, insertions, deletions, and the full range of single-nucleotide changes, which could provide new ways to edit disease-causing genes and broaden the therapeutic potential for genomic medicines. Rewrite also has developed an approach that could improve the efficiency of genome editing in non-dividing cell types, a key challenge for some existing editing platforms. Rewrite’s technology could potentially be delivered using Intellia’s lipid nanoparticle (LNP) technology and adeno-associated virus (AAV) vectors.

https://www.biospace.com/article/releases/intellia-therapeutics-announces-acquisition-of-rewrite-therapeutics/

Viatris-Mylan 1st to Receive FDA Approval of Generic Restasis for Dry Eye

 Viatris Inc. (NASDAQ: VTRS) today announced that its subsidiary, Mylan Pharmaceuticals, Inc., has received approval from the U.S. Food and Drug Administration (FDA) for its Abbreviated New Drug Application (ANDA) for Cyclosporine Ophthalmic Emulsion 0.05%, the first generic version of Allergan's Restasis®. There are no remaining legal or regulatory barriers, and the company is launching immediately.

CRISPR and ViaCyte Dose First Patient in Historic Type 1 Diabetes Trial

 CRISPR Therapeutics and ViaCyte have announced that they dosed their first patient in Phase I clinical trial of novel gene-edited cell replacement therapy to treat Type 1 Diabetes (T1D). The drug, VCTX210, is an investigational, allogenic (patient-derived), gene-edited, immune-evasive, stem cell-derived therapy intended to help T1D patients produce their insulin.

In patients with T1D, the body’s immune system mistakenly attacks healthy pancreatic cells that produce insulin. Patients with T1D must take prescription insulin to maintain normal blood sugar levels because their body can no longer do so on its own.

By combining CRISPR Therapeutics’ gene-editing technology and ViaCyte’s proprietary pluripotent stem cell line, the companies have developed VCTX210, which produces pancreatic cells designed to evade recognition from the immune system, prohibiting them from being destroyed by an aberrant immune system. The cell line will be differentiated into pancreatic endoderm cells, generating glucose-responsive insulin-secreting cells in the patient.

VCTX210 will most likely be delivered via a PEC-Direct pouch, a product candidate developed by ViaCyte. The pouch is designed for blood vessels to enter the device and directly interact with implanted cells. Direct vascularization allows for robust and consistent engraftment. Because the cells are designed to be immune evasive, the companies do not expect them to be rejected by the immune system.

The Phase I clinical trial of VCTX210 will assess the safety, tolerability and immune evasion in patients with T1D. Ten participants will be included in the trial estimated to be completed in December 2022.

CRISPR Therapeutics and ViaCyte have produced this program as part of a strategic collaboration to discover, develop, and commercialize gene-edited stem cell-derived therapies. The companies hope that these therapies can provide a functional cure for people with T1D and those with insulin-requiring Type 2 Diabetes without immunosuppression.

“We are excited to work with CRISPR Therapeutics and ViaCyte to carry out this historic, first-in-human transplant of gene-edited, stem cell-derived pancreatic cells for the treatment of diabetes designed to eliminate the need for immune suppression,” said James Shapiro, M.D., Ph.D., Canada research chair, director of the Islet Transplant Program at the University of Alberta, Canada, and a clinical investigator in the trial. “If this approach is successful, it will be a transformative treatment for patients with all insulin-requiring forms of diabetes.”

https://www.biospace.com/article/crispr-and-viacyte-announce-phase-i-clinical-trial-for-type-1-diabetes/

Future of Key Asset in Question as Gilead Reveals More Holds

 A week after safety issues forced a partial clinical hold on the combination of magrolimab plus azacitidine as a potential treatment for myelodysplastic syndrome (MDS), Gilead Sciences revealed in a call with analysts that the hold has now been expanded to additional magrolimab studies, raising questions about the future of that drug.

Magrolimab is a potential first-in-class investigational monoclonal antibody against CD47 and a macrophage checkpoint inhibitor. The asset was at the center of Gilead Sciences’ $4.9 billion acquisition of Forty Seven, Inc. in 2020. As an oncology asset, magrolimab is designed to interfere with the recognition of CD47 by the SIRPĪ± receptor on macrophages, to block the “don’t eat me” signal used by cancer cells.

The partial clinical hold placed last week by the U.S. Food and Drug Administration was based on what Gilead Sciences called “an apparent imbalance” in investigator-reported, suspected unexpected serious adverse reactions (SUSARs). In that study, magrolimab was paired with the Bristol Myers Squibb chemotherapy drug azacitidine, marketed under Vidaza and Onureg. Out of a sense of caution at the time, Gilead Sciences placed all studies assessing the combination on clinical hold until the safety data can be analyzed.

Now, partial clinical holds have been placed on two other studies assessing magrolimab that are not in combination with the Vidaza. During the company’s earnings call this week, Chief Medical Officer Merdad Parsey reported that a partial clinical hold was also placed on the Phase II multiple myeloma study and a fully-enrolled Phase II diffuse large B-cell lymphoma (DLBCL) study. Parsey said the Phase II multiple myeloma study had not begun to enroll patients when the hold was placed.

Parsey also noted that a Phase I b study assessing magrolimab in MDS has been halted. He said there is no longer a viable path to submission based on regulatory feedback. Existing data from the Phase Ib study will be presented later. Parsey said the company remains focused on its Phase III ENHANCE study in the same indication.

“Importantly, patients currently enrolled in our magrolimab studies can continue treatment, and our compassionate use programs remain open. We are working with FDA to take a comprehensive look at the safety data, and we’ll share the outcome as quickly as we can,” Parsey said, according to a transcript of the call. “In the meantime, we remain committed to the magrolimab development program and believe that it has the potential to address an important unmet medical need in these seriously ill patients. As you know, the patients in our ENHANCE Phase III trial have a very high unmet need, with a median overall survival of only one to three years on the current standard of care.”

Parsey noted that the FDA wants to look at the entirety of safety data generated so far in the magrolimab studies. He explained in the call that he is blinded to the data itself, but what investigators have available will be shared with the FDA and the data monitoring committee. Parsey added that the safety concerns are seen as “temporary challenges” right now and the company plans to resolve them as quickly as possible.

“I don’t think these challenges really shake our confidence for the portfolio overall, and our overall strategy hasn’t changed. We’re really committed to the magro development program, and we think that it really continues to have the potential to really address an important unmet medical need,” he said.

https://www.biospace.com/article/more-holds-hit-cancer-drug-at-center-of-gilead-sciences-2020-buyout-of-forty-seven-inc-/