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FDA Fires Broadside At CytoDyn Over COVID-19 Antibody Data

In a rare move, the FDA has publicly accused US biotech CytoDyn of misrepresenting clinical trial results for leronlimab, an antibody being developed for COVID-19. 

It's not uncommon for drug developers put a positive spin on lacklustre clinical data, but CytoDyn's attempts seems to have irritated the US regulator, specifically relating to its use of subgroup analyses to try to indicate a benefit for leronlimab.

The biotech has run two studies to try to repurpose HIV and cancer candidate leronlimab as a COVID-19 therapy, neither of which achieved their primary objectives, but has said it will nevertheless file the data with regulators in countries including India and the Philippines.

The 86-patient CD10 trial looked at the antibody's potential in mild-to-moderate COVID-19, but failed to show a benefit on any measures, including the primary endpoint of "total clinical symptom score", encompassing fever, muscle aches, shortness of breath, and cough, according to the FDA.

Leronlimab was also no better than placebo when it came to secondary endpoints including survival, time to symptom resolution, and time to return to normal activity.

A larger trial involving 394 severe to critically ill COVID-19 patients – called CD12 – also failed to find any effect of the drug on the main endpoint (mortality) or secondary measures such as the length of time patients spent in hospital, said the agency.

In its analysis, CytoDyn zeroed in on a subgroup of 62 critically ill patients on ventilation who were treated with the CCR5 antagonist, arguing that it significantly reduced all-cause mortality, and achieved a six-day reduction in hospital stay.

The FDA begs to differ, saying: "the data from CD12 illustrated imbalances in mortality among subgroups, some favouring leronlimab and some favouring placebo."

It adds that "none of these analyses met statistical significance when using established and reliable analytical methods that correct for multiple comparisons."

Unsurprisingly given that assessment, the regulator turned down CytoDyn's request for emergency-use authorisation of leronlimab in critically-ill patients, although it has said it will meet with the company to discuss the design of another trial.

"With the conclusion of both the CD10 and CD12 clinical trials, it has become clear that the data currently available do not support the clinical benefit of leronlimab for the treatment of COVID-19," said the regulator.

Shares in the company fell sharply after the FDA issued its statement, prompting the company to hold an investor meeting to state its case, and published updated results from the study that it says reinforce the benefits of the drug and show it hit most secondary endpoints.

CEO Nader Pourhassan said repeatedly on the call that the company was grateful to the FDA for its input, that there was no factually incorrect information in the agency's statement, and that he was embarrassed by questioning that implied the company was at odds with the regulator.

He added that the company had decided not to pursue development in the US because there are relatively few critically ill patients there, but that situation is different in countries like India, the Philippines and Brazil.

A Brazilian trial in 300-plus critically ill patients is underway, said Pourhassan, adding that will likely be required for approval, while additional evidence from studies may also be needed in India.

At the moment the situation for the emergency use application in the Philippines is still in flux, he said, but it might be possible to secure that on the strength of the updated CD12 results.

Complicating the picture, CytoDyn is also facing a class action lawsuit claiming the company made false and misleading statements about leronlimab's potential in COVID-19. It has said it will "vigorously defend" itself against any such accusations.

CytoDyn Announces FDA Clearance Of Phase II Oncology Trial

CytoDyn (CYDY) announced that it has received clearance from the FDA to commence its Phase II oncology trial. The study will evaluate the efficacy of leronlimab in patients with relapsed/refractory microsatellite stable colorectal cancer, CRC. This milestone reflects the continued positive development of the Company's improved relationship with the FDA. Clearance for the Phase II oncology trial was achieved following productive feedback sessions with the FDA over the past few months and the submission of a final study protocol to the FDA in September 2024. As previously announced, the trial will be conducted in partnership with Syneos Health. A trial kickoff meeting has been set for late November 2024 and patient enrollment will begin in early 2025.

Breast Cancer That Comes Back Is Especially Deadly. A New Trial Seeks To Prevent It

When Jamie LaScala turned 40 in 2015, she didn't think she needed a mammogram just yet, but a friend encouraged her to go.

"I was right on the cusp of when you're supposed to start getting the mammograms," LaScala, now 49, tells TODAY.Com. "My best friend had been nagging me because sadly she had friends in her neighborhood who started to get diagnosed."

She felt stunned when her first mammogram came back as abnormal. "There was no breast cancer in my family," she says.

That led to a diagnosis of Stage 3 triple-positive, inflammatory breast cancer, "a fairly rare and aggressive subtype," LaScala explains. "At 40, that was young to be diagnosed, and I was definitely surprised."

She started chemotherapy immediately and responded well. Then, she underwent a mastectomy and radiation. She's now on hormone therapy and has no evidence of disease.

But as time has passed, she's stopped undergoing regular scans to look for possible recurrence. (Such scans are usually only recommended for about five years.) Like many patients, she still worries that her cancer will return.

"In my case, it's just been if something comes up as a concern, we check it out, but it's not a regular scan," she says. "There's an element, of course, of a lack of control."

Since her diagnosis, LaScala has become a patient advocate and participated in a clinical trial seeking to help prevent breast cancer recurrence, something experts still don't fully understand.

Since her diagnosis, Jamie LaScala has become a patient advocate for research, supporting breast cancer investigators and encouraging patients to participate in clinical trials.Courtesy Jamie LaScala

Majority of women with breast cancer, about 90%, are diagnosed with "just a bump in the breast or in the breast and the lymph nodes under the arm," Dr. Angela DeMichele, one of the leaders of the study, CLEVER, that LaScala participated in, tells TODAY.Com. These cases can be anywhere from Stage 1 to 3.

About 70-80% of these women will be cured, thanks to the current therapies — including chemotherapy, radiation and anti-estrogen treatments, DeMichele, co-director of the 2-PREVENT Breast Cancer Translational Center of Excellence at Penn Medicine's Abramson Cancer Center, adds.

In the other 20-30%, the breast cancer will return as Stage 4, also known as metastatic, when the cancer has spread to other parts of the body beyond the lymph nodes near the breast. Metastatic breast cancer is much harder to treat, with about 31% of patients surviving longer than five years, per the American Cancer Society.

But predicting which patients' cancer will come back as Stage 4 can be challenging.

"The problem is that we don't know who those women are until it happens," DeMichele says. "When that cancer comes back, it's coming back in the lungs or the liver or the bone — someplace outside of the breast — and it is incurable."

What's more, data shows a recent increase in women being diagnosed with breast cancer at younger ages. And breast cancer in young women, especially those under 35, is more likely to recur, according to Mayo Clinic.

Risk factors for breast cancer recurrence

Many women with breast cancer want to undergo a double mastectomy out of fear the breast cancer will come back in their breasts. But the bigger concern is that the cancer will come back in the bones, liver or lungs, as metastatic disease is much harder to treat, Dr. Eric Winer, director of the Yale Cancer Center, explains.

To understand which patients might be more likely to experience metastatic breast cancer recurrence, doctors consider several factors about a patient's cancer.

Cancer in the lymph nodes

In early-stage breast cancers, if the cancer has spread to a lymph node, that may be an indicator of future metastatic disease, Winer says.

"If it's moved to a lymph node, it's already telling you it wants to travel," Dr. Arif Kamal, chief patient officer at the American Cancer Society, adds.

Stage 0 and 1 breast cancers do not involve lymph-node spread, meaning earlier detection remains helpful in preventing recurrent metastatic disease.

Grade of the cancer

While cancer stage refers to how far it's spread, the cancer's grade measures how abnormal the cancer cells are compared to healthy cells, according to MD Anderson Cancer Center.

"Is it angry-looking under the microscope? Does this look like a troublemaker cancer?" Kamal says. "In grade, we are looking at how quickly it is dividing and how abnormal does it look?"

Cancer subtype

Inflammatory, like LaScala had, and triple-negative breast cancers are more likely to recur, according to Cleveland Clinic.

Size of the tumor

Kamal notes that a larger tumor — think 3 centimeters versus 1 centimeter — could increase the risk of metastatic breast cancer in the future. That's because doctors suspect that a larger tumor has lived in the body for longer, he explains.

Stage of the cancer

"The risk of metastatic disease is higher for people with higher-stage cancers," Kamal says. Later-stage cancers have already spread to the lymph nodes, are more likely to cause a larger tumor, and often look "highly aggressive" under a microscope, he adds.

Genetic mutations

Genetic mutations, such as a BRCA1 or 2 mutation or Lynch syndrome, can increase the risk of breast cancer recurrence.

In fact, many women with genetic mutations are recommended to undergo double mastectomies to prevent recurrence in the same or opposite breast because the risk is that much higher.

People with multiple first-degree relatives who've had breast or ovarian cancer or any cancer before age 50 may also be higher risk for cancer recurrence and therefore undergo a double mastectomy.

For the rest of the population with earlier-stage cancers, data tends to show that a lumpectomy and radiation has an equal survival rate to double mastectomy, Winer says.

A clinical trial to find "sleeping" cancer cells

After LaScala learned about a clinical trial at Penn Medicine with the goal of preventing metastatic recurrence of breast cancer, she wanted to participate. She hoped that by being a part of research, she could help herself and others.

"An area of emotional and psychological burden for patients is (the) whole idea that, 'OK, I'm done with treatment. … Now what?'" she explains.

For most people diagnosed with breast cancer, conventional treatments work well to prevent recurrence. "The problem was that we didn't really know what to do (after) the end of that initial therapy that was designed to get a patient to the point where they don't have any cancer," DeMichele says, adding that the plan is often "watchful waiting."

Regular scans to detect new cancer continue typically for about five years. Then patients are left to wonder what comes next.

In an effort to create a more active approach to prevent recurrence, DeMichele's colleagues identified specialized cells that can escape the breast and move into the bloodstream and aren't affected by treatment. These cells are in a "dormant or sleeping state," but can later re-activate into metastatic breast cancer, she explains.

"One of the places they like to go is the bone marrow," DeMichele says. "Once they hit the bone marrow, they find that a very supportive place to just burrow in, stop dividing and essentially hibernate."

DeMichele and her collaborators wondered if there was a way to detect these sleeping cells and treat them before they awake and move to other parts of the body and turn into cancer. They started a study monitoring women's bone marrow and treating those who had the sleeping cells in it.

Jamie LaScala's son, now in high school even attends medical conferences with his mom to learn about the latest breast cancer research.Courtesy Jamie LaScala

For the study, LaScala underwent yearly bone marrow aspiration, when researchers collect and analyze bone marrow cells. For several years, her tests were clear of the sleeping cancer cells, but then in 2018, researchers found some and put her on a medication to wipe them out, hopefully reducing the chance of her cancer coming back.

"The clinical trial was testing two different drugs that are specific to these dormant cells," DeMichele says. "We saw that both drugs could eliminate the sleeping cells, and about 80% of those patients are doing very well."

She notes that these treatments seem to work no matter the type of breast cancer. But the therapies used in this phase-2 clinical trial are geared toward preventing recurrence of an original breast cancer, and not new diagnosis.

"(Recurrence) is what (most) people die of who have breast cancer," DeMichele says.

The trial is being expanded to phase 3 and enrolling more patients. DeMichele is hopeful more people will be interested in participating.

"Patients want this information. They want to be proactive," she says. "It's just waiting for that shoe to drop that is so distressing to people."

DeMichele says they hope to have trial results in a few years, and they'll also need to refine the testing protocol to make it work for patients if it becomes widely available.

"We're still working out what the surveillance would look like to be able to do this testing," she says. "We'll probably have to do it repeatedly over a period of time to make sure that they're really clear."

Advocating for others

LaScala has been a patient advocate since her diagnosis, focusing on research and education. She often attends medical meetings where she learns about the latest in breast cancer research.

"(I) support (and) encourage our researchers because they dedicate really their lives to helping improve patient outcomes," she says. 

By sharing her story, LaScala hopes that more patients look at clinical trials as an opportunity to help expand the understanding of breast cancer and create innovative treatments.

"Part of this cancer journey is knowing that there are things we can't control, but we certainly can do everything we can for ourselves and for our fellow patients and keep supporting that ongoing research," LaScala says.

"There are just so many trials for early (and) late-stage so getting involved ... Was really eye-opening and exciting. That's why I try to continue to support research as an advocate."

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