J&J Secures Full FDA Approval for Bladder Cancer Drug Balversa

 Johnson & Johnson announced on Friday that the FDA has granted its FGFR kinase inhibitor Balversa (erdafitinib) full approval for the treatment of locally advanced or metastatic urothelial carcinoma.

Friday’s full approval amends Balversa’s previous indication, which allowed its use in patients with susceptible mutations on the FGFR3 or FGFR2 genes, after platinum-based chemotherapy, according to the FDA’s announcement of the approval.

J&J’s pill is now indicated for patients with susceptible genetic alterations on the FGFR3 gene—as determined by an approved test—with disease progression after at least one prior line of systemic therapy. Balversa is not approved to treat patients who are eligible for, but have not yet undergone, PD-1 or PD-L1 inhibitor therapies.

Designed to be taken orally once-daily, Balversa is a small molecule FGFR kinase inhibitor that works by targeting and binding to FGFR1, FGFR2, FGFR3 and FGFR4, blocking their enzymatic activity, according to J&J’s website. This mechanism of action cuts off several signaling cascades and suppresses the uncontrolled division and survival of cancer cells.

Balversa won the FDA’s accelerated approval in April 2019 for certain types of locally advanced or metastatic urothelial carcinoma (mUC), becoming the first FDA-authorized FGFR inhibitor. At the time, Balversa was backed by findings from a small single-arm Phase II trial with 87 enrolled patients, demonstrating a 32.2% objective response rate and a median duration of response of 5.4 months.

To keep Balversa on the market, J&J ran the confirmatory Phase III THOR trial, which enrolled nearly 630 patients and compared the oral FGFR kinase inhibitor against the standard of care regimen, consisting of chemotherapy or Merck’s Keytruda (pembrolizumab). Patients who had undergone at least one prior line of anti-PD-(L)1 therapy were assigned to Cohort 1 of THOR, while those who had not were placed in Cohort 2.

Data from Cohort 1, which ultimately became the basis for the FDA’s full approval on Friday, showed that Balversa cut the risk of death by 36% versus chemotherapy. Patients in the Balversa arm also lived a median of four months longer than those on chemotherapy, an effect that was statistically significant, according to J&J’s announcement.

Kiran Patel, vice president of clinical development, solid tumors at J&J Innovative Medicine, said in a statement that “Balversa continues to demonstrate the promise of targeted therapy in the treatment of cancer with advanced bladder cancer,” given its performance in THOR.

Friday’s full approval for Balversa continues J&J’s winning streak in cancer. In December 2023, the pharma posted promising data from the Phase III PERSEUS study showing that a Darzalex Faspro-based quadruplet regimen could significantly improve progression-free survival in newly diagnosed multiple myeloma patients.

In October 2023, J&J’s head-to-head MARIPOSA study showed that the combination of Rybrevant and lazertinib could potentially best AstraZeneca’s Tagrisso (osimertinib) in EGFR-mutated non-small cell lung cancer.

https://www.biospace.com/article/j-and-j-secures-full-fda-approval-for-bladder-cancer-drug-balversa/

Gilead’s ADC Trodelvy Fails Phase III NSCLC Study

 While antibody-drug conjugates have been a significant focus of dealmaking in 2023 and early 2024, Gilead Sciences on Monday announced a setback for its ADC Trodelvy (sacituzumab govitecan-hziy) which did not hit the mark in a late-stage clinical trial.

In the Phase III Evoke-01 study, Trodelvy failed to meet the endpoint of overall survival in previously treated metastatic non-small cell lung cancer patients when put up against the chemotherapy docetaxel.

Gilead said it will explore “potential pathways” to “further understand the role” the drug has in these patients. While the complete numbers from the trial were not made immediately available, the company said it plans to discuss the trial with regulators and that the data will be presented at an upcoming medical meeting.

However, the market did not react well to the news Monday morning, as Gilead’s stock price dropped by nearly 10%.

“The totality of our data gives us continued confidence in Trodelvy’s potential in metastatic NSCLC and our broader lung cancer clinical development program,” Gilead CMO Merdad Parsey said in a statement. “Treating metastatic NSCLC that has progressed on or after platinum-based chemotherapy presents significant challenges, and the need for safe and effective treatments remains urgent. We will work to identify further the metastatic NSCLC patient populations that may benefit from Trodelvy.”

Gilead tried to put a positive spin in Monday’s announcement noting a more than three-month difference in median overall survival favoring Troldelvy was observed in a “sub-group of patients non-responsive to last prior anti-PD-L1 therapy.” Gilead is still confident in its NSCLC program, claiming it has seen “strong preliminary efficacy” from a Phase II combo of Trodelvy and Keytruda (pembrolizumab).

The FDA approved Trodelvy in February 2023 to treat breast cancer, showing a 30% reduction in disease progression or death risk in 2022.

Though Trodelvy has not been approved by any regulatory agency for the treatment of metastatic NSCLC, Gilead said in Monday’s announcement that it is the first approved Trop-2-directed ADC “that has demonstrated meaningful survival advantages in two different types of metastatic breast cancers and improved clinical outcomes for certain people with 2L metastatic urothelial cancer.”

While the ADC market has been on a hot streak in oncology, mainly through heavy M&A activity, Gilead has not only been developing its internal treatments but also taking the acquisition route. In 2020, the company acquired Immunomedics  in $21 billion buy, giving Gilead access to Trodelvy.

The ADC space continues to be hot in early 2024 as Roche inked a potential $1 billion deal with China-based MediLink Therapeutics to develop an ADC in oncology earlier this month.

https://www.biospace.com/article/gilead-s-adc-trodelvy-fails-phase-iii-nsclc-study-stock-drops-10-percent-/

Evotec call

  Evotec SE (Frankfurt Stock Exchange:EVT, MDAX/TecDAX, ISIN: DE0005664809; NASDAQ:EVO) is going to hold a conference call to provide a statement as well as a business update on Monday, 22 January 2024.

During the call, the Chairwoman of Evotec's Supervisory Board, Prof. Iris Löw-Friedrich and Evotec's CEO Dr Mario Polywka will offer the Company's perspective on its commitment to comply with highest Corporate Governance standards and its dedication to well-balanced and transparent communication to all market participants. The statement will be limited to Evotec's scope of influence.

Dr Mario Polywka will also share management's conviction to execute on the existing strategy, recent developments in the market and the reasoning behind unchanged views on Guidance 2023 and the 2025 outlook.

Webcast details

Date: Monday, 22 January 2024
Time: 3.00 pm CET (02.00 pm GMT, 09.00 am EST)

To join the audio webcast and to access the presentation slides, please register via this link.

The on-demand version of the webcast will be available on our website: https://www.evotec.com/en/investor-relations/ir-events.

Conference call details

To join via phone, please pre-register via this link. You will then receive a confirmation email with dedicated dial-in details such as telephone number, access code and PIN to access the call.

https://www.accesswire.com/viewarticle.aspx?id=826892

Abivax provides 2024 strategic outlook and lays out key milestones

 

• Induction data read-out expected Q1 2025 from the pivotal Phase 3 ABTECT program evaluating obefazimod in moderately to severely active ulcerative colitis (UC)
• Formal process evaluating oral and injectable combination therapy candidates with obefazimod in UC has commenced; preclinical data to support decision-making on combination agent expected in 2H 2024
• Top-line data from long-term extension trial with 25mg obefazimod once-daily oral after one and two years of treatment expected to read-out in Q3 2024
• IND for Phase 2 trial of obefazimod in Crohn’s disease (CD) cleared; Abivax to consider protocol modifications based on FDA recommendations
• Obefazimod follow-on candidate selection expected in Q3 2024

https://www.biospace.com/article/releases/abivax-provides-2024-strategic-outlook-and-lays-out-key-milestones-over-next-12-months/

Global Regulators Increase CAR T Scrutiny in Wake of FDA’s Investigation

 In November 2023, the FDA announced it was investigating the “serious risk” of malignancies in patients who have been treated with BCMA- or CD19-directed autologous CAR-T cell immunotherapies. The announcement has garnered attention from regulatory authorities and industry leaders in regions including South Korea, the EU and the U.K. 

Chimeric antigen receptor (CAR) T cell therapy was developed more than three decades ago by Carl June, an immunologist at the University of Pennsylvania who wanted to circumvent the adverse effects of bone marrow transplants used in treating blood cancers. Today, six CAR T cell therapies—Novartis’ Kymriah, Johnson & Johnson/Janssen’s Carvykti, Bristol Myers Squibb’s Abecma and Breyanzi and Gilead/Kite’s Tecartus and Yescarta—have been approved for various blood cancers and 217 more are in Phase II clinical trials and later stages of development for different cancers.

All six approved therapies are covered under the FDA’s safety investigation.

Tightening Global Regulations

A European Medicines Agency (EMA) representative told BioSpace in an email that "a thorough review of all available evidence is ongoing" by the Pharmacovigilance Risk Assessment Committee (PRAC), an EMA arm that assesses and monitors medicines.

“This includes the 23 cases of various types of T-cell lymphoma or leukemia that were present in EudraVigilance at the time of signal validation,” the representative said, adding that these cases overlap with ones reported to the FDA.

In a statement emailed to BioSpace, Janine Jolly, deputy director of benefit/risk evaluation at the U.K.’s Medicines and Healthcare Products Regulatory Agency (MHRA), said the regulator is aware that the FDA and the EMA’s PRAC are investigating a signal of serious risk of T-cell malignancy following treatment with BCMA-directed or CD19-directed autologous CAR T cell immunotherapies. She noted that secondary malignancies are considered a potential risk for products in this class. However, she said the MHRA “will consider this issue further and communicate any new advice to healthcare professionals and patients upon completion of our review.” 

An FDA representative told BioSpace in an email that while the potential risk of developing secondary malignancies is indeed labeled as a class warning in the U.S. prescribing information for approved CAR T cell immunotherapies, “the FDA’s safety communication describes reports specifically of T-cell malignancy.”

Further east, South Korea announced in December 2023 that it is monitoring the side effects of the two CAR T cell therapies approved in that country, Kymriah and Carvykti.

“The Korean regulatory agencies will now be more focused on receiving expansive data regarding malignancies as well,” said Sasmitha Sahu, a pharma analyst at GlobalData who covers immunology and oncology, in a GlobalData report.

Sahu told BioSpace that South Korea’s Ministry of Food and Drug Safety (MFDS) appears to design its regulatory policies based on FDA guidelines. However, unlike in the U.S. and Europe, where there are observatory units for tracking CAR T cell therapy’s adverse effects, South Korea does not yet have such checkpoints in place because the medicines were recently approved in the country.

“It is not clear what kind of active steps the South Korean agencies have taken, but they have definitely directed hospitals where these CAR T cell therapies are administered to closely track incidents or the appearance of secondary malignancies,” Sahu said. “The mandated monitoring of all the reporting of any suspected adverse reactions, including T-cell malignancies [and] adverse effects, may lead to the creation of a similar dedicated registry for patients who are administered CAR-T therapies.”

The FDA requires 15 years of patient follow-up for all approved CAR-T therapies to monitor their long-term safety profile. Following the reports of T cell malignancies in patients who had previously received CAR-T therapies, the regulator recommended life-long surveillance. “Monitoring [CAR T cells] could slow down the regulatory enthusiasm across all the regions,” Sahu said. “It may prompt the need to do a cautious wait-and-watch approach and may elicit further changes in the regulatory approval process.”

In an email to BioSpace, a representative for Gilead said, “We are confident in the overall benefit-risk profile of both Yescarta and Tecartus, having treated 17,700 patients to date in both clinical trials and the commercial setting. There is no evidence to date that treatment with Yescarta or Tecartus has a causal role in the development of malignancies of T-cell origin.”

In a similar vein, the FDA representative said, “The overall benefits of these products continue to outweigh their potential risks for their approved uses.” A global group of cancer and cell therapy leaders concluded the same in a commentary recently published in Nature, while stressing that more information is needed.

Perception: Pros and Cons

Shriya Das, a biotech professional who managed one of Advenchen Laboratories’ Phase I and II oncology clinical trials in South Korea and Japan, said that while current clinical trials will go ahead as planned, it may take longer to fill them. “Everybody reads newspapers, everybody is aware of what's happening. Recruitment could slow down because patients and potential participants could get a scare about trying a new investigational treatment.”

Das additionally noted that the therapies will face stronger scrutiny by regulatory authorities moving forward. However, she said, even if the FDA does find concerning evidence, the investigation could provide valuable data and insights for developing more-effective and safer treatments, ultimately leading to better patient outcomes. Another benefit of the FDA’s investigation is that it will build the public’s confidence in regulatory authorities, Das said, as patients will see that medicines are still monitored after approval.

https://www.biospace.com/article/global-regulators-increase-car-t-scrutiny-in-wake-of-fda-s-investigation-/

Coherus to Divest Ophthalmology Franchise to Sandoz

  Coherus BioSciences, Inc. (“Coherus,” NASDAQ: CHRS) today announced it has entered into an agreement to divest its CIMERLI® (ranibizumab-eqrn) ophthalmology franchise, inclusive of CIMERLI and its supporting commercial infrastructure, to Sandoz for upfront, all-cash consideration of $170 million plus an additional amount for CIMERLI product inventory and subject to customary working capital adjustments at the closing date. This divestiture includes Coherus’ CIMERLI biologics license application, ophthalmology sales and select field reimbursement teams, CIMERLI product inventory on hand, and access to proprietary commercial software.

When: Monday, January 22, 2024, starting at 8:30 a.m. Eastern Time

To access the conference call, please pre-register through the following link to receive dial-in information and a personal PIN to access the live call: https://register.vevent.com/register/BI6503dff137704129b680ec1b80115c2b
Please dial-in 15 minutes early to ensure a timely connection to the call.

Webcast Link: https://edge.media-server.com/mmc/p/cpa5veqh
A replay of the webcast will be archived on the “Investors” section of the Coherus website at http://investors.coherus.com.

https://www.globenewswire.com/news-release/2024/01/22/2812687/33333/en/Coherus-Announces-Agreement-to-Divest-Ophthalmology-Franchise-to-Sandoz-in-170-Million-Upfront-All-Cash-Deal.html

With chronic absenteeism soaring, educrats still tell students school isn’t that important

 The Biden administration Wednesday announced its plan to attack the latest education scourge: chronic absenteeism.

“We cannot and will not accept that as a new normal,” the White House said, referring to double-digit truancy rates.

Two days later, Washington and surrounding suburbs once again showed students how important the adults really think school is: They canceled classes for no reason. 

“DC Public Schools will be closed,” Mayor Muriel Bowser abruptly announced Friday morning.

The nominal reason was snow. 

But it didn’t snow much. DC got fewer than four inches, which fell calmly and steadily through the afternoon.

There were no wind or visibility problems; it wasn’t bitterly cold.  

Even with the district’s casual approach to plowing and even without heavy-duty winter gear, roads and sidewalks were perfectly passable by car and on foot. 

Nor was this a “better safe than sorry” fizzled-out forecast: It was never supposed to snow very much.

The local government’s decision to close schools left more than 50,000 students — most of them black or Hispanic, half of them “at risk,” according to various government homeless and welfare criteria — home, many alone, with nothing to do.

(The district didn’t even pretend kids would do “remote learning.”)

The closures left parents and grandparents with no child care, though we keep hearing how important child care is.  

And it was the second snow day in a week, meaning that after the MLK holiday Monday, kids who need to get on a normal schedule after the Christmas break had just two days of school last week.  

Even as DC closed schools Friday, it made it clear the adults would go on with their important business.

The rest of the DC government was open as normal (as it was last week’s first snow day). 

The federal government had a two-hour delay.

Museums, stores and restaurants were open on time.

The city was quiet, but it wasn’t empty.

The March for Life, with its tens of thousands of attendees from out of town and attendant security needs and media coverage, went on.

The House speaker and other members of Congress spoke at the outdoor rally.  

The anti-abortion marchers made it clear by being there in person: We think what we are doing matters.

By contrast, once again, the school-bureaucracy adults, while pretending school is important, demonstrated to children — through their actions, not words — school isn’t that important. 

Children have already absorbed this lesson.

Last school year, 43% of DC students missed 10% or more of school days, up from a not-so-great 30% before COVID.  

As in the rest of the country, after missing 18 months of school starting in March 2020, kids without solid support systems at home got out of the habit of going to school.

Chronic absenteeism nationwide is about 28%, double pre-pandemic levels. 

If you don’t go to school, you don’t learn much: The White House estimates chronic absenteeism is responsible for a quarter to nearly half of the recent cratering of math and reading test scores. 

But it’s not just that.  

A failure to keep kids to a normal schedule has resulted in more teen depression, antisocial behavior and crime.

Last year, Washington murders hit a quarter-century high, with 274 killed; 16 victims were children.

Teens and young adults, who were teens during the pandemic, are responsible for a huge uptick in carjackings, robberies and assaults as well.  

Yes, suburban school and private schools also closed Friday — and no, that’s not good either.

Whether rich or poor, white or black, kids have learned over the past four years that adult bureaucracies really don’t care what happens to them.  

But middle-class and wealthier kids have more nongovernment resources.

If you attend Sidwell Friends, where former President Barack Obama’s daughters went, your parents probably found something for you to do or someone to watch you Friday. 

The Biden administration can lament low attendance and brag about the billions it has directed to school districts to help combat it.

The fancy ideas are home visits, “high-dose tutoring” and more summer-school and after-school programs.   

Here’s one idea: Make school districts keep the schools open, every day, absent a declaration of national disaster or lose a lot of federal funding as punishment.  

Nicole Gelinas is a contributing editor to the Manhattan Institute’s City Journal.

https://nypost.com/2024/01/21/opinion/with-chronic-absenteeism-soaring-educrats-still-tell-students-school-isnt-that-important/