Myovant Sciences rejects $2.5 bln takeover bid from Sumitovant, Sumitomo Pharma

  Myovant Sciences Ltd said on Sunday it rejected a $2.5 billion takeover offer from Sumitovant Biopharma and its parent group Sumitomo Pharma Co Ltd as the bid "significantly undervalues" the U.S. drugmaker.

Sumitovant, which currently holds approximately 52% of the outstanding shares in Myovant Sciences, and Sumitomo Pharma had submitted a proposal to acquire the remaining shares in the drugmaker for $22.75 per share in cash, according to a statement.

The special committee has carefully reviewed the proposal and determined that it significantly undervalues the company and is not in the best interests of the company or its minority shareholders, Myovant Sciences said, adding it remains open to considering any improved proposal that reflects the "full and fair value" of the firm.

The proposed acquisition consideration represents an equity value of $2.4 billion and an enterprise value of $2.5 billion, Sumitovant Biopharma said in a separate statement. 

https://finance.yahoo.com/news/1-myovant-sciences-rejects-2-004047768.html

Bubs Australia seeks permanent market access from U.S. FDA

 Baby formula maker Bubs Australia Ltd said on Monday it is seeking permanent access to the U.S. market after the Food and Drug Administration (FDA) spelled out how companies that have been filling a temporary shortage can become long-term suppliers.

Bubs said it had lodged a letter of intent with the U.S. FDA for permanent market access to October 2025 and beyond, adding that the FDA will issue a letter of acknowledgement in response.

Global infant formula manufacturers have been importing goods into the United States after the country's health regulator relaxed its import policy to address a nationwide shortage partly triggered by Abbott Laboratories' manufacturing plant in Michigan recalling some products in February.

The U.S. health regulator on Friday published guidance to help provide a pathway for infant formula manufacturers operating under enforcement discretion in the United States to remain in the market.

The FDA said manufacturers currently marketing their products in the country under enforcement discretion should send a letter to the FDA by Dec. 5, 2022, outlining their intent to pursue completion of all regulatory requirements.

"Some manufacturers may have most of the information needed to meet all U.S. requirements, and therefore, could achieve compliance fairly quickly, while others may need the full time frame being provided," the U.S. health regulator said.

https://sports.yahoo.com/bubs-australia-seeks-permanent-market-230144088.html

A lot of folks are running the White House. Joe Biden just isn't one of them

 Joe Biden isn’t as lively as he used to be. Not exactly breaking news, but it seems to be getting worse.

At 79, Biden is our oldest president. He consistently stumbles and misspeaks, forcing his beleaguered staff to retract his statements or pretend the lapse never happened.

Speaking at a White House conference on food, nutrition and health on Wednesday, Biden acknowledged the elected officials who helped organize the event.

“I want to thank all of you here for including bipartisan elected officials like Rep. (Jim) McGovern, Sen. (Mike) Braun, Sen. (Cory) Booker, Representative – Jackie, are you here?” Biden said, looking around the crowd. “Where’s Jackie? I think she wasn’t going to be here – to help make this a reality.”

He was looking for Rep. Jackie Walorski, R-Ind., who was killed in a tragic car accident in early August. A death he commemorated at the time in a solemn White House statement.

Where's Biden? Not often in the White House

White House press secretary Karine Jean-Pierre refused to acknowledge any mistake was made, despite repeated questions from the gathered reporters.

Add in Biden’s early “lids,” four-day weekends and frequent vacations, and he doesn’t seem to be running things. About 40% of his days have been away from the White House, including two-thirds of August.

I’ve known several older folks who were sharper at 80 than I was at 40. Joe Biden is not one of them. This isn’t about his age as much as his competence. To blame his behavior on a childhood stutter – a favorite excuse in 2020 – insults all Americans.

Perhaps we should be thankful. Considering inflation, energy shortages and a world teetering on the brink, maybe the less Biden is involved, the better.

Regents often ruled in place of the king

To understand what’s happening, it’s best not to think of this as a Biden Presidency, but a Biden Regency.

The term was regularly used in the age of kings and empires. If an 8-year-old princess was placed on the throne or an incapable king couldn’t perform his duties, one or several regents would handle the day-to-day operations.

Many a royal adviser would ignore a capable successor, instead crowning a child so the courtiers could run things behind the scenes.

One regency served during the reign of King George III, most famous for losing the Revolutionary War. After several concerning incidents, his mental health collapsed. George remained king on paper, but the Parliament appointed his heir as Prince Regent.

The dissolute prince decided he would rather party than rule, so he happily let the advisers run the show. The regency ran the empire for the next decade.

Whoever's running things, they aren't doing it well

In like manner, Biden is surrounded with longtime D.C. power players, such as Ron Klain, Susan Rice, Anita Dunn, John Podesta, Gene Sperling – a veritable “who’s who” of Beltway knife fights and insider skullduggery. Throughout their long careers, they’ve never sought credit or voter approval. Just power.

And the less Joe is around, the more their regency can accomplish.

Not that these new courtiers always agree. Journalists spend their days trying to determine which of them is rising and who is falling – D.C.’s version of Cold War “Kremlinology.”

These competing power centers explain the contradictory policies coming out of the Oval Office these days. Aggressively pushing a new Iran Nuclear Deal while Russia buys Iranian drones to fight Ukrainians. When there’s no one to say “the buck stops here,” the bucks turn up in pretty strange places.

It reminds me of the confusing end of Woodrow Wilson’s presidency. For his last 18 months in office, he was incapacitated with a stroke. First lady Edith Wilson and a handful of confidantes covered it up and ran the country themselves.

As with Wilson, historians will one day explain the Biden Regency more fully. But someone is running the country, and not very well.

Jon Gabriel, a Mesa resident, is editor-in-chief of Ricochet.com and a contributor to The Republic and azcentral.com.

https://www.azcentral.com/story/opinion/op-ed/2022/10/01/joe-biden-absent-minded-president-who-runs-white-house/10460695002/

NFLPA fires doctor, agrees to change concussion protocols after Tagovailoa injury

 The NFL’s player’s union has fired a doctor and agreed with the league on changes to the league’s concussion protocols amid backlash over a concussion suffered by Miami Dolphins quarterback Tua Tagovalioa.

Tagovalioa appeared to suffer a head injury last weekend, but was allowed to continue playing. He then started for the Dolphins just four days later, and suffered a chilling concussion in a game against the Cincinnati Bengals that caused his hands to seize up

The third-year quarterback was carted off the field and admitted to a nearby medical facility before being discharged later that night. 

“The NFL and the NFLPA agree that modifications to the Concussion Protocol are needed to enhance player safety,” the NFL and its players’ union, the NFLPA, said in a joint statement on Sunday.

“The NFLPA’s Mackey-White Health & Safety Committee and the NFL’s Head Neck and Spine Committee have already begun conversations around the use of the term ‘Gross Motor Instability’ and we anticipate changes to the protocol being made in the coming days based on what has been learned thus far in the review process.” 

The statement follows the NFLPA dismissing a neurotrauma consultant on Friday who was involved in the concussion protocol check of Tagovalioa after his first injury during a game against the Buffalo Bills, according to NFL.com. 

The reasons for the dismissal reportedly included failure to understand his role and hostility during the investigation into the injuries, which remains ongoing.

The 2018 Heisman Trophy winner returned to the Bills game and led his team to victory, with the team saying it was actually his back that bad been injured and that he cleared concussion protocols to return.

ut when he suffered another injury days later, fans and pundits erupted in criticism of the Dolphins organization and concern about the impact on Tagovalioa’s future.

In a statement on Friday, Tagovalioa thanked fans for the good wishes and added he’s feeling much better and is focused on returning to the field soon.

https://thehill.com/blogs/blog-briefing-room/3671327-nflpa-fires-doctor-changes-concussion-protocols-after-tagovailoa-injury/

ADC Offers Promising Results in Relapsed or Refractory Hodgkin Lymphoma

 Investigational camidanlumab tesirine led to a high response rate in heavily pretreated patients with relapsed or refractory classical Hodgkin lymphoma (HL), according to results from a phase II trial.

With a median follow-up of 10.7 months, the drug demonstrated an overall response rate (ORR) of 70.1% among 117 patients who were refractory or had relapsed after a a median of six prior treatments, including brentuximab vedotin (Adcetris) and PD-1 blockade, reported Alex F. Herrera, MD, of City of Hope Comprehensive Cancer Center in Duarte, California.

A complete response (CR) was achieved in one-third of patients, while the partial response (PR) rate was 36.8%, and 17.9% of patients achieved stable disease, he said in a presentation at the Society of Hematologic Oncology (SOHO) annual meeting.

Camidanlumab tesirine is an antibody drug conjugate comprising a human IgG1 anti-CD25 monoclonal antibody conjugated to a pyrrolobenzodiazepine (PBD) dimer.

"Several patients experienced a long-lasting treatment effect. Most responses were observed after two cycles and 15 patients who initially had a partial response ultimately had a complete response," Herrera stated.

But adverse events (AEs) were an issue. Almost every (99%) patient in the study had a treatment-emergent AE, with skin rash the most common. The most common grade ≥3 treatment-emergent AEs were cytopenias. All-grade treatment-emergent AEs related to the PBD dimer included skin and nail reactions (74.4% of patients), hepatobiliary test abnormalities (29.1%), and edema/effusion (17.1%).

Over half of patients (56.4%) had treatment-emergent AEs leading to dose delays or reductions, while 27.4% had treatment-emergent AEs leading to discontinuation. Four patients had treatment-emergent AEs leading to death, none of which were deemed related to camidanlumab tesirine, according to Herrera and colleagues.

Immune-related AEs occurred in 32.5% of patients, with grade ≥3 AEs occurring in 10 patients. These came on after a median of about 3.5 cycles of camidanlumab tesirine, and half emerged more than 30 days after last dose, Herrera said.

Eight patients developed Guillain-Barré syndrome (GBS) or polyradiculopathy. Herrera pointed out that "there was not a clear signal for baseline characteristics that were associated with Guillain-Barré." However, he noted that with prompt management, such as IV immunoglobulin, plasma exchange, and/or high-dose steroids, GBS resolved in four of eight patients, and decreased in severity to grade 1 in three.

Still, SOHO session moderator Alison J. Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York City, commented that the agent's activity is "quite high, and its frustrating that we see the toxicity associated with it, and its seems to be pretty unpredictable."

"Where do you see this drug as far as in the treatment course for Hodgkin in the future?" she said.

Herrera responded that "the toxicities are real. It's an active drug and we have a lot of patients in a tough spot, so I think [the agent] has a role -- it will have to be a role that is maybe a bridge to something else, or a palliative bridge if there's not an intention for transplant."

"Patients will just have to be monitored carefully," he added. "As we learn more about how to use this agent, we'll be able to stop therapy earlier, especially since most of the responses have been early."

Herrera explained that all but one patient in the trial had previously received brentuximab vedotin and a checkpoint inhibitor. Of the 73 patients who previously received brentuximab vedotin and checkpoint inhibition with prior haematopoietic stem cell transplant (HSCT), 74.0% achieved a response with camidanlumab tesirine (95% CI 62.4%-83.5%). This included a CR rate of 41.1%, a PR rate of 32.9%, and a stable disease rate of 17.8%.

In the 43 patients who previously got brentuximab and checkpoint inhibition without prior HSCT, the ORR with camidanlumab tesirine was 62.8% (95% CI 46.7%-77.0%), which included an 18.6% CR rate, a 44.2% PR rate, and a 18.6% stable disease rate.

Herrera also reported that the median duration of response (DOR) was 13.7 months and median PFS was 9.1 months. Patients who achieved a CR had a median DOR 14.5 months and a median PFS 15.9 months.

Fourteen patients discontinued treatment to proceed to transplant. Of the patients who received a transplant, 11 received allogeneic transplants. Of the latter, three progressed 2-5 months after transplant. Four received autologous transplants, with one progression 2 months after transplant.

The single-arm, multicenter, open-label trial enrolled patients with a pathologic diagnosis of classical HL who had relapsed disease. Patients were required to have received at least three previous lines of systemic therapy, or two or more lines of prior therapy if ineligible for HSCT. Patients had a median age 37, 62.4% were male, and 95% had an ECOG score of 0 or 1.

Camidanlumab tesirine was administered at a dose of 45 μg/kg via a 30-minute IV infusion on day 1 of each 3-week cycle for cycles 1 and 2. For cycles 3 and on, patients received the agent at a dose of 30 μg/kg for up to 1 year.

Disclosures

The study was funded by ADC Therapeutics SA.

Herrera dislcosed relationships with, and/or support from, AbbVie, Adicet Bio, AstraZeneca, ADC Therapeutics, BMS, Caribour, Genentech/Roche, Genmab, Karyopharm, Merck, Pfizer, Seattle Genetics, Takeda, Tubulis, Bristol Myers Squibb, Gilead, and KiTE Pharma.

Primary Source

Society of Hematologic Oncology

Source Reference: Carlo-Stella C, et al "Camidanlumab tesirine: Updated efficacy and safety in an open-label, multicenter, phase 2 study of patients with relapsed or refractory classical Hodgkin lymphoma" SOHO 2022; Abstract HL-339.

https://www.medpagetoday.com/meetingcoverage/soho/101011

Calls to Team Heart Failure Specialists With Cardiac Critical Care

 With the needs of advanced heart failure (HF) dwarfing the supply of skilled physicians, HF specialists and others are well-positioned to prove their value in the contemporary cardiac ICU (CICU) -- and the clock is ticking for training and accreditation to keep up.

The problem for the workforce is that CICU patients are increasingly complex and affected by HF. More and more people are entering CICUs with congestive HF and cardiogenic shock, accompanied by comorbid sepsis and liver failure and an increasing need for non-cardiac procedures such as bronchoscopy, mechanical ventilation, and renal replacement therapy.

"CICUs are becoming the HF unit whether people want to acknowledge it or not," said Jason Katz, MD, MHS, co-director of the CICU and MCS program at Duke University in Durham, North Carolina, during a discussion at the Heart Failure Society of America (HFSA) annual meeting.

Problems meeting the uniquely resource-intensive care needs of patients with advanced HF and mechanical circulatory support are exacerbated lately by pandemic-related staffing issues, according to Ann Gage, MD, director of the CICU at Centennial Medical Center in Nashville.

As there just aren't enough dual-boarded critical care cardiologists -- or critical care doctors in general, for that matter -- the hope is that advanced HF-trained cardiologists might help fill the talent gap in the CICU if they learn to manage critically ill patients during training.

Katz noted that he is dual boarded-certified in advanced HF and critical care. He contrast the fewer than 50 training spots each year for critical care cardiologists with the over 80 programs training one to five HF cardiologists ever year.

There are incentives for HF specialists to make the jump: during this period of dwindling appeal and job uncertainty in advanced HF as a career -- the "elephant in the room" -- HF doctors should strengthen their niche in critical care, suggested Rachna Kataria, MD, of Rhode Island Hospital and Brown University in Providence. Kataria is a recent advanced HF transplant cardiology (AHFTC) fellowship graduate.

"We need to rebrand ourselves...We're not just [ventricular assist device] and transplant physicians," said Kataria. "Critical care training should be a core competency at this point."

She said that HF fellows should get more clinical training in areas such as post-cardiac surgery management, mixed shock and neurologic emergencies, and palliative care. They should also enrich skills in intubation, bronchoscopy, airway and ventilator management, and anesthesia during their training, she added.

Ultimately, it will take leadership to implement safety initiatives and quality improvement studies to show that HF cardiologists are not a liability in critical care, but that they bring value to patients, according to Kataria.

Katz noted that the specific components in each program will need to be tailored to fit the institution's needs and demands.

He cited a proposed pathway in which interested trainees pass through internal medicine residency and general cardiology fellowship before reaching AHFTC fellowship embedding cardiac critical care. At the end, they can be board-certified in cardiology and AHFTC with a distinction in cardiac critical care, he said.

He acknowledged the barriers to getting doctors interested in the AHFTC-cardiac care fellowship -- training fatigue, relocation, and having fellows waiting another year before they can start paying off their student loans.

As such, some believe there is room for more nurse practitioners and physician assistants to step into the CICU team. These providers currently have few options for advanced HF-specific training, yet structures are being put in place to encourage them down this path.

The Mayo Clinic Arizona in Scottsdale has a 1-year physician assistant fellowship for advanced HF, which could serve as a model for future efforts, for instance. And the HFSA is also launching a HF certification specifically for advanced practice providers in the next few months, according to Shannon Cornell, A-NP, of Medical University of South Carolina in Charleston.

For now, Katz urged stakeholders to engage professional societies like the American College of Cardiology to develop new training pathways and determine what is necessary for the future of cardiac critical care.

"Until that time, it's the Wild Wild West," he said. "We're flying by the seat of our pants."

Disclosures

Katz, Gage, Kataria, and Cornell disclosed no relationships with industry.

Primary Source

Heart Failure Society of America

Source Reference: "Many Roads Lead to Rome: Evolving Training Pathways for the Advanced Heart Failure and Critical Care Cardiologist" HFSA 2022.

https://www.medpagetoday.com/meetingcoverage/hfsa/101013

Cholera kills at least seven in Haiti as disease returns

 

Haiti on Sunday said at least seven people have died of cholera in a surprise return of the disease that comes as the nation is paralyzed by a gang blockade that has triggered shortages of fuel and clean drinking water.

The disease killed some 10,000 people through a 2010 outbreak that has been blamed on a United Nations peacekeeping force. The Pan American Health Organization in 2020 said Haiti had gone a year with no confirmed cholera cases.

"According to the information we have, the number of deaths is about 7 to 8," he said, adding that officials were struggling to get information from hospitals. "There was one death during the day today."

The Health Ministry earlier confirmed one case in the Port-au-Prince area and that there were suspect cases in the town of Cite Soleil outside the capital, which was the site of vicious gang turf wars in July.

Gangs have since last month been blocking the country's main fuel port in protest over last month's announcement of a fuel price hike. Many hospitals have shut down or scaled back operations for lack of fuel to power generators.

Basic transit is now impossible for most citizens.

Caribbean Bottling Company, a key supplier of bottled water, said on Sunday that it could no longer continue producing and distributing water because it had run out of diesel fuel, which is critical to its supply chain.

Cholera causes uncontrollable diarrhea.

The disease is typically spread by water contaminated with the feces of a sick person, meaning that clean drinking water is critical for preventing its spread.

Troops from Nepal, where cholera is endemic, were in Haiti as part of a U.N. peacekeeping force established in 2004 after the overthrow of President Jean-Bertrand Aristide. The force size was increased after Haiti's 2010 earthquake.

The United Nations in 2016 apologized for the outbreak, without taking responsibility.

An independent panel appointed by then-U.N. Secretary General Ban Ki Moon issued a 2011 report that did not determine conclusively how cholera was introduced to Haiti.

    The panel members in 2013 independently published an article that concluded personnel associated with the U.N. peacekeeping mission were "the most likely source."

https://www.marketscreener.com/news/latest/Cholera-kills-at-least-seven-in-Haiti-as-disease-returns--41910230/