#ASCO21: Novartis gears up for CAR-T fight with Gilead in follicular lymphoma — safety may be crucial

 Since winning the first CAR-T approval in the US back in 2017, Novartis has been hard at work expanding the reach of its blockbuster cancer drug Kymriah. Gilead’s Yescarta beat it to the punch in follicular lymphoma (FL) back in March — but now, Novartis says it has new pivotal data that could give its old rival a run for its money.

Of 94 patients given Kymriah for relapsed or refractory FL, 86% responded, according to primary results released ahead of ASCO 2021. A total of 66% saw a complete response — which is just a bit higher than the 65% Novartis touted upon sharing interim results from the Phase II ELARA trial back in December.

These new efficacy results include nearly twice as many patients as the interim analysis, Novartis said. The overall response rate also saw a small bump, up from the 83% rate recorded in December. Median duration of response, progression free survival, and overall survival were not yet reached, according to Novartis.

Despite some familiar efficacy figures, Kymriah could set itself apart on the safety front. No patients experienced Grade 3 or 4 cytokine release syndrome, a well-documented side effect of CAR-T therapy. Those results top Yescarta’s ZUMA-5 data, which showed Grade 3 or higher CRS in 8% of patients.

Grade 1 or 2 CRS occurred in 49% of patients in ELARA, with 9% of patients experiencing Grade 1 or 2 neurological events. One patient experienced Grade 4 neurological events, but recovered. Three participants died from progressive disease, though none of the deaths were treatment-related, according to the Swiss pharma.

Novartis plans on running the new data to regulators “as quickly as possible,” according to Stefan Hendriks, the global head of Novartis Oncology’s cell and gene division. He confirmed in an email to Endpoints News that a submission for the new indication will come sometime this year.

FL is the second most common form of non-Hodgkin lymphoma, with a five-year survival rate of only 20% for patients in the third line and later. Patients with FL have malignant tumors that grow slowly and can become more aggressive over time, and efficacy of available treatments drops off rapidly in later lines. Patients in ELARA had a median of four prior treatments, though some had taken as many as 13.

Yescarta won approval as a third-line therapy back in March, becoming the first CAR-T approved for relapsed/refractory FL. The OK was based on results from the ZUMA-5 trial, in which 91% of patients saw a response, 60% of whom achieved a complete remission, according to Gilead. Median duration of response had not been reached.

“As you know, direct cross trial comparisons are methodically and statistically not appropriate due to differences in patient characteristics, efficacy outcome measures (timing) and in-patient vs. out-patient setting,” Hendriks said in an email. “Head-to-head studies have not been performed, and no comparison of safety and efficacy can be made.”

While Kymriah beat Yescarta out the gate back in 2017, Yescarta has the upper hand in sales, at least in Q1 of this year. The Gilead drug pulled in $160 million last quarter, while Kymriah made Novartis $151 million.

https://endpts.com/asco21-novartis-gears-up-for-car-t-fight-with-gilead-in-follicular-lymphoma-and-safety-could-define-the-battle/

BARDA looks to get jump on next pandemic with VC arm targeting 'transformative' tech

 Five years after Congress first called for it — and a year and a half after a pandemic broke out — BARDA, the US’s top pandemic preparedness agency, is launching its own VC fund.

The new fund will invest in technologies that could be deployed against future outbreaks or other public health emergencies. It follows a similar model to other public health VCs, such as the Gates Foundation’s fund, giving capital to early-stage companies with promising platform technologies in exchange for assurances they use it partly for infectious diseases that might not have a significant market.

Sandeep Patel, director of BARDA’s division of Research, Innovation and Ventures, name-checked mRNA vaccines, a technology that was being developed in large part for cancer before Covid-19, but which another branch of the government — DARPA — invested in as a pandemic preparedness tool.

It’s “looking at what’s potentially transformative,”  he told Endpoints News. “mRNA represented a kind of new class of vaccines. What’s the equivalent of that we can invest in for the future, either in vaccines, treatments or diagnostics? Or even things that cut across those areas.”

Fittingly for a long-overlooked government agency dependent on Congress for cash, the fund is for now modest. BARDA has committed only $10 million this year and $50 million over the next five years to the VC, although Patel said that they hope to raise that up to $500 million over the next decade. He noted that President Joe Biden’s new budget includes $50 million for year one of the effort, should it be passed.

They also plan to match their own investments with private capital. Congress authorized the VC fund in 2016 as part of the 21st Century Cures Act, but Patel said they needed time to figure out its model. After soliciting bids in the fall, the agency announced it will team with GHIC, a Gates-funded non-profit that will look to marshal more conventional VCs to burnish BARDA’s efforts.

Despite its pre-pandemic history, the new fund fits into a broader push to develop technologies, infrastructure and other capabilities to prevent the next pandemic, joining government and academic efforts to develop pan-viral vaccines and industry efforts to reimagine biologics manufacturing, so any future pandemic vaccine or treatment could be rapidly scaled.

It’s a departure from where BARDA has spent much of the funds in the past, when it directed tens of millions of dollars to get individual products — often antibiotics without an immediate commercial market — through late-stage studies.

Patel said they’ll invest in companies — around five to nine per year — that have clearer commercial applications outside of public health emergencies, so it will be sustainable without heavy public funding and ready if a crisis strikes. As with other non-profit venture efforts, any returns from those investments would be funneled back into the fund to be re-invested. He compared it to In-Q-Tel, the CIA’s VC arm.

What could those technologies or companies be? Patel wouldn’t dive into too many specifics, but he threw out needle-free vaccines, which BARDA has already modestly invested in,  and new methods for rapidly scaling manufacturing — anything that could turned around faster for Covid-28, or whatever strikes next.

“There’s a lot, there’s a long list here, we’re in the process of setting priorities,” Patel said. “Clearly Covid-19 has showed us some lessons.”

https://endpts.com/barda-looks-to-get-the-jump-on-next-pandemic-with-vc-arm-targeting-transformative-tech/

Breast-Cancer Pill Reduced Recurrence, Death in Early-Stage Patients: Study

 A drug sold by AstraZeneca PLC and Merck & Co. reduced the recurrence of breast cancer in women with an early but aggressive form of the disease, a long-running international study found.

The finding, which on Thursday was published online by the New England Journal of Medicine and released at a major cancer-research meeting, marked the latest advance in cancer treatments targeting the genetic traits of tumors. It could expand the arsenal of weapons against a hereditary form of breast cancer.

The result also helps validate the pharmaceutical industry's investment in a pricey new class of drugs that target cancer cells, known as PARP inhibitors.

AstraZeneca's pill, named Lynparza, has become one of the company's top sellers, generating $1.8 billion in sales last year. Rival GlaxoSmithKline PLC paid more than $5 billion in 2019 to acquire the maker of another PARP inhibitor, Tesaro.

Lynparza carries a U.S. list price of about $14,449 per patient monthly.

AstraZeneca plans to submit the data to regulators and request regulatory approval of the use of Lynparza for early-stage BRCA breast cancer, said David Fredrickson, executive vice president of AstraZeneca's oncology unit.

PARP inhibitors work by blocking cancer cells from relying on a survival tactic: the ability to repair their own DNA after their DNA is damaged naturally or by other drug treatments. This, in turn, contributes to cancer-cell death.

Health regulators have approved these types of drugs in recent years to treat ovarian, breast, prostate and pancreatic cancers.

The drugs have been found to be particularly useful against cancers associated with harmful mutations in genes known as BRCA1 and BRCA2. Women with these hereditary mutations have a higher risk of developing breast cancer, and often at a younger age than is typical.

The BRCA mutations account for about 5% of the estimated 281,000 cases of breast cancer diagnosed annually in the U.S.

Overall, breast cancer is the second leading cause of cancer death in women, causing about 43,600 deaths in the U.S. annually, according to the American Cancer Society.

The Food and Drug Administration cleared Lynparza, in 2018, to treat advanced-stage BRCA-mutated breast cancer.

The new study tested Lynparza in women at earlier stages of breast cancer, at a time when it is potentially curable. AstraZeneca sponsored the study and collaborated with Merck and various research groups that run breast-cancer clinical trials.

Starting in 2014, researchers in the U.S. and 22 other countries enrolled 1,836 women with early-stage BRCA1 or BRCA2 breast cancer.

Before enrolling in the study, the women had undergone surgery to remove tumors, and had received chemotherapy before or after surgery aimed at preventing a recurrence of the tumor. They were at high risk of recurrence based on the size of their tumors or presence of cancer in lymph nodes.

The women also tested negative for the HER2 gene that is present in some breast cancers.

Half of the women in the study were randomly assigned to take Lynparza tablets daily for one year, while the other half got a placebo.

At a median follow-up period of 2 1/2 years after the start of treatment, Lynparza reduced the combined risk of recurrence of cancer or death from any cause by 42% compared with a placebo, the researchers found.

Researchers estimated that three years after the start of treatment, 85.9% of the women who received Lynparza were living without disease recurrence, compared with 77.1% of women who received a placebo.

Lynparza also improved other measures of benefit, including the time from the start of treatment until the development of tumors distant from the original site in the breasts.

There were fewer deaths among the Lynparza patients than among women who received the placebo, 59 versus 86, but the difference didn't meet the study's criteria for statistical significance at the time of follow-up.

Researchers said it may be possible at future dates to demonstrate a statistically significant improvement in overall survival.

"The early results are very encouraging that these therapies may indeed result in increased cures for patients who develop cancers with these mutations," said Dr. Charles Geyer, deputy director of the Houston Methodist Cancer Center and one of the study's leaders.

The presence of BRCA mutations can be detected with a blood test. "This further highlights the importance of genetic testing in appropriate patients, so that we know which patients will benefit from this therapy, " ASCO President Dr. Lori J. Pierce said in an online briefing with reporters.

Patients receiving Lynparza had higher rates of certain adverse events including nausea, fatigue and anemia, compared with those who received placebo, the study found. Researchers said this was consistent with the safety profile of the drug for other uses.

AstraZeneca had previously disclosed in February that the study was positive but didn't report the full results until Thursday, ahead of being presented at the annual meeting of the American Society of Clinical Oncology. The New England Journal of Medicine also simultaneously published the results online.

AstraZeneca initially developed the drug. In 2017, it formed a partnership with Merck to further develop and co-market the drug.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/Breast-Cancer-Pill-Reduced-Recurrence-Death-in-Early-Stage-Patients-Study-Finds-35515273/

Abbott Labs Plans Restructuring Due to Changes in Covid-19 Testing Demand

 Abbott Laboratories on Thursday said it approved a restructuring plan last month "to align its manufacturing network for Covid-19 diagnostic tests with recent changes in projected testing demand."

In a filing with the U.S. Securities and Exchange Commission, the company said the changes in projected testing demand have been driven by several factors, including reductions in cases in the U.S. and other major developed countries and accelerated rollout of Covid-19 vaccines globally.

The company also said it estimates pretax costs to implement its plan to be about $550 million to $700 million. "The costs are expected to be incurred during the remainder of 2021 with the majority of the costs expected to be recorded in the second quarter of 2021," Abbott said, adding "The costs will be treated as specified items."

Earlier this month, Abbott updated to its financial outlook for the full year. At that time, Robert B. Ford, the company's president and chief executive, said "We've recently seen a rapid decline in Covid-19 testing demand and anticipate this trend will continue, which led us to adjust our full-year guidance."

https://www.marketscreener.com/quote/stock/ABBOTT-LABORATORIES-11506/news/Abbott-Labs-Plans-Restructuring-Due-to-Changes-in-Covid-19-Testing-Demand-35515301/

NANOBIOTIX Reports New Data for Potential First-in-Class Radioenhancer NBTXR3 Combo

 Data to be Presented at the 2021 Annual Meeting of the American Society for Clinical Oncology

• Results show NBTXR3 plus radiotherapy could potentially stimulate immune response and convert anti-PD-1 non-responders into responders
• Objective response was observed in 60% of anti-PD-1 naïve patients and 50% of prior non-responders
• Data suggest abscopal effect in some patients (i.e., reduction in non-injected / non-irradiated lesions)
• To date, the overall adverse event profile for the 16 injected patients has not differed from what is expected with radiotherapy or anti-PD-1 agents (head and neck cancer and non-small cell lung cancer primary tumors)
• New readout could provide promising signals for NBTXR3 as a potential pillar of immunotherapy
• Following ASCO, Nanobiotix will host an investor event on Friday, June 11, 2021 at 8:00 am Eastern Time (14:00 Central European Time), to provide an in-depth review of the immunotherapy data with several key opinion leaders including study investigators (Register here)

https://www.streetinsider.com/Business+Wire/NANOBIOTIX+Reports+New+Data+for+Potential+First-in-Class+Radioenhancer+NBTXR3+in+Combination+With+Anti-PD-1+Showing+Local+or+Distant+Tumor+Regression+in+76.9%25+of+Evaluable+Patients+Regardless+of+Prior/18518508.html

‘Next big wave’: Radiation drugs track and kill cancer cells

 Doctors are reporting improved survival in men with advanced prostate cancer from an experimental drug that delivers radiation directly to tumor cells.

Few such drugs are approved now, but the approach may become a new way to treat patients with other hard-to-reach or inoperable cancers.

The study tested an emerging class of medicine called radiopharmaceuticals, drugs that deliver radiation directly to cancer cells. The drug in this case is a molecule that contains two parts: a tracker and a cancer-killing payload.

Trillions of these molecules hunt down cancer cells, latching onto protein receptors on the cell membrane. The payload emits radiation, which hits the tumor cells within its range.

“You can treat tumors that you cannot see. Anywhere the drug can go, the drug can reach tumor cells,” said Dr. Frank Lin, who had no role in the study but heads a division at the National Cancer Institute that helps develop such medicine.

Results were released Thursday by the American Society of Clinical Oncology ahead of its annual meeting this weekend. The study was funded by Novartis, the drug’s maker, which plans to seek approvals in the United States and Europe later this year.

When cancer is confined to the prostate, radiation can be beamed onto the body or implanted in pellets.

But those methods don’t work well in more advanced prostate cancer. About 43,000 men in the United States each year are diagnosed with prostate cancer that has spread and is no longer responding to hormone-blocking treatment.

The study tested a new way to get radiation treatment to such patients.

It involved 831 men with advanced prostate cancer. Two-thirds were given the radiation drug and the rest served as a comparison group. Patients got the drug through an IV every six weeks, up to six times.

After about two years, those who received the drug did better, on average. The cancer was kept at bay for nearly nine months compared to about three months for the others. Survival was better too — about 15 months versus 11 months.

The gain may not seem like much, but “these patients don’t have many options,” said ASCO president Dr. Lori Pierce, a cancer radiation specialist at the University of Michigan.

Radioactivity can reduce blood cell production, which can lead to anemia and clotting problems for patients. In the study, 53% of the patients had serious side effects compared to 38% of patients in the comparison group. Both groups were allowed to get other treatments.

The results pave the way for government approval and will boost interest in radiation drugs, Lin said.

Others already in use include Novartis’ Lutathera for a rare type of cancer of the stomach and gut.

And Bayer’s Xofigo is approved for men whose prostate cancer has spread to the bone but not elsewhere. Xofigo targets areas where the body is trying to repair bone loss from tumor damage, but it isn’t directly aimed at prostate cancer cells wherever they may be in the body.

Since the experimental drug targets tumor cells, “that would be a first for prostate cancer,” Lin said.

In the coming decade, such drugs “will be a major thrust of cancer research,” said Dr. Charles Kunos, who worked on standards for radiopharmaceutical research at the National Cancer Institute before leaving to join University of Kentucky’s Markey Cancer Center. “It will be the next big wave of therapeutic development.”

“There’s great potential” with drugs being tested for melanoma and breast, pancreatic and other cancers, said Dr. Mary-Ellen Taplin of Dana-Farber Cancer Institute in Boston, who enrolled patients in the study and reviewed the data.

As for prostate cancer, “it opens up a range of future strategies,” including at earlier stages of disease and alongside other treatments, said study leader Dr. Michael Morris of Memorial Sloan Kettering Cancer Center in New York.

https://apnews.com/article/cancer-science-business-health-54e08ed1a440669a88932aba505d2e54

Senseonics Study: Strong Accuracy of 180 Day CGM Sensor

 Senseonics Holdings, Inc. (NYSE-American: SENS), a medical technology company focused on the development and commercialization of the first and only long-term, implantable continuous glucose monitoring (CGM) system – the Eversense® CGM System – today announced the results of the PROMISE Study evaluating the accuracy and safety of the next generation Eversense CGM System for up to 180 days with reduced calibrations. The data was presented by Satish Garg, MD, Professor of Medicine at the Barbara Davis Center of the University of Colorado, Denver, and the study group Principal Investigator (PI), as an oral presentation at the 14th Annual ATTD Meeting. Results were presented for both the primary sensor and for a secondary sensor with modified chemistry (referred to as the SBA sensor) in a subset of study participants.

https://www.businesswire.com/news/home/20210603005866/en/Senseonics-Announces-Results-of-the-PROMISE-Study-Demonstrating-Strong-Accuracy-of-180-Day-CGM-Sensor