Search This Blog

Monday, August 9, 2021

Reata updates on clinical programs

 Recent Company Highlights

Omaveloxolone in Patients with Friedreich’s Ataxia ("FA")

Based on a communication received from the U.S. Food and Drug Administration ("FDA") regarding omaveloxolone for the treatment of FA, we withdrew our request for a Type C meeting and requested a pre-NDA meeting with the FDA. The pre-NDA meeting request has been granted, a pre-NDA meeting has been scheduled during the third quarter of this year, and we have submitted briefing materials for the meeting. We recently received a communication from the FDA requesting the estimated date of our New Drug Application ("NDA") for its planning purposes. We plan to submit the NDA during the first quarter of 2022.

Bardoxolone Methyl ("Bardoxolone") in Patients with Alport Syndrome

The NDA for bardoxolone for the treatment of patients with chronic kidney disease ("CKD") caused by Alport syndrome is currently under review by the FDA. The FDA completed a bio-research monitoring inspection of Reata. We did not receive any observations. We also recently completed a mid-cycle communication meeting with the FDA. While we have not yet received formal minutes from the FDA, in the preliminary agenda for, and during, the meeting, the FDA identified four significant clinical and statistical review issues for us to address. The FDA invited us to respond to its identified issues in follow-up submissions to the NDA, and we believe each of the identified issues is addressable with additional data and analyses. The FDA did not designate any safety issues as significant issues, and it stated that, based on its current review, it does not believe a Risk Evaluation and Mitigation Strategies ("REMS") program is needed. The FDA also advised us that an Advisory Committee meeting is tentatively scheduled for December 8, 2021. The Prescription Drug User Fee Act ("PDUFA") date, the FDA action date for the application, is scheduled for February 25, 2022.

Conference Call Information

Reata’s management will host a conference call on August 9, 2021, at 4:30 pm ET. The conference call will be accessible by dialing (866) 270-1533 (toll-free domestic) or (412) 317-0797 (international) using the access code: 10157197. The webcast link is https://event.on24.com/wcc/r/3196578/57A5A4A99C3D3BA0F2D6A7D9D86B06B7.

Second quarter financial results to be discussed during the call will be included in an earnings press release that will be available on the company’s website shortly before the call at https://www.reatapharma.com/investors/ and will be available for 12 months after the call. The audio recording and webcast will be accessible for at least 90 days after the event at https://www.reatapharma.com/investors/.

https://finance.yahoo.com/news/reata-pharmaceuticals-inc-announces-second-200100847.html

California to offer vaccine incentive to Medicaid population

 California announced another round of coronavirus vaccine incentives on Friday, offering up to $50 apiece to more than 11 million people in the state who get their health insurance through Medicaid.

The money is part of a new $350 million plan to get more of the state’s Medicaid population vaccinated as the state is seeing a surge of new cases attributed to the delta variant, a more contagious and dangerous version of the coronavirus. Medicaid is the joint state and federal health insurance program for people who are disabled or have low incomes.

Many states have used tax dollars to entice people to get the coronavirus vaccine. States like Massachusetts, Michigan and Ohio offered up to $1 million in a lottery-style drawing among those who had received the vaccine.

In California, Gov. Gavin Newsom’s administration doled out $116.5 million in incentives earlier this year, including $1.5 million each for 10 people and $50,000 payments for another 30 who had received the vaccine. The state is handing out $50 gift cards to grocery stores to people who got vaccinated between May 27 and July 18, plus free tickets to Six Flags theme parks.

California is among the states with the highest vaccination rates, with about 76% of residents 12 and over having received at least one dose of the vaccine. However, only 45% of the state’s Medicaid population has been vaccinated.

“We’re working extremely hard to improve vaccination rates, but we believe we can do better, and must do better, to prevent further disparities in COVID-19 infection and death among persons served by (Medicaid),” state Medicaid Director Jacey Cooper said.

California’s Medicaid program is the largest in the country with more than 13.8 million people. But the incentives announced Friday will apply to about 11.7 million people who get their health insurance from private companies, who are then paid by the state.

California is offering those companies $250 million in incentives if they increase the vaccination rates among their members. The state has also set aside $100 million for incentive payments to people, which can’t exceed $50 each. Coper said most likely those payments would be in the form of grocery store gift cards.

Several groups of Medicaid beneficiaries have low vaccination rates, including people who are homebound, have multiple chronic diseases, people of color and people between the ages of 50 and 64 and 12 and 25, Cooper said.

The goal of the incentives, Cooper said, is to spur the private insurance companies who manage the bulk of the state’s Medicaid plans to get more of those people vaccinated. That could include having more primary care doctors offer the vaccine at their offices and partnering with community organizations and food banks.

“We need to work through harder to reach beneficiaries and figure out how we can make it more convenient,” Cooper said.

https://apnews.com/article/lifestyle-health-coronavirus-pandemic-medicaid-1ceffb57b08a15a38ec03bf332e3ba30

US turns to social media influencers to boost vaccine rates

 As a police sergeant in a rural town, Carlos Cornejo isn’t the prototypical social media influencer. But his Spanish-language Facebook page with 650,000 followers was exactly what Colorado leaders were looking for as they recruited residents to try to persuade the most vaccine-hesitant.

Cornejo, 32, is one of dozens of influencers, ranging from busy moms and fashion bloggers to African refugee advocates and religious leaders, getting paid by the state to post vaccine information on a local level in hopes of stunting a troubling summer surge of COVID-19.

Colorado’s #PowertheComeback target audience is especially tailored to Latino, Black, Native American, Asian and other communities of color that historically have been underserved when it comes to health care and are the focus of agencies trying to raise vaccination rates.

It’s part of a growing U.S. state- and city-based movement using local social media influencers to reach the most vaccine-hesitant at a neighborhood level. Health authorities in Chicago, Oklahoma City, San Jose, California, New Jersey and elsewhere are running similar campaigns.

The effort comes after Colorado and other states have tried lotteries, college scholarships and other incentives to boost slumping vaccination rates as the highly contagious delta virus variant sweeps the nation.

Cornejo’s Facebook page has become a widely trusted source of information about what the police do — and cannot do — for Latinos in the Colorado River Valley.

“It started last year when I saw misinformation that directly affected our department, rumors like police were arresting people without a mask,” said Cornejo, a 10-year veteran with the Rifle Police Department. “Or that people get magnetized when they’re vaccinated. Sometimes people are just plain scared. I give them fact-based information, nothing political about it, so they can make an informed decision.”

Whether the social media push will move the needle with America’s unvaccinated remains to be seen.

The country last week reached the milestone of having at least one dose in 70% of adults. It came a month after President Joe Biden’s target date, even though most can easily get the shots in the U.S. unlike other countries where they’re in short supply.

“I’m highly skeptical you can get enough appeal to the remaining 30% of adults who after all this time have not gotten the vaccine — it’s a lot to ask of an influencer,” said Jeff Niederdeppe, director of Cornell University’s Health Communication Research Initiative and co-director of The Cornell Center for Health Equity.

More likely to tip the scales is an increase in private companies and organizations requiring vaccinations of employees and patrons, he said.

In Colorado, the state pays citizen influencers up to $1,000 a month for their work on Instagram, TikTok, Snapchat, Facebook and other platforms. The influencers post about their own vaccine experiences, dispel myths and misinformation, alert followers to pop-up vaccine clinics and direct them to information provided by state health authorities.

Abena Antwiwaa, a 29-year-old fashion blogger in Aurora, wrote about her nerve-wracking decision to get vaccinated on Instagram. Born with sickle cell anemia, Antwiwaa needs monthly blood transfusions. She worried about her low immunity and potential side effects.

“I was so nervous about getting vaccinated, and I shared that experience,” said Antwiwaa, who suffered nothing more than a temporarily sore arm. “It resonated with a lot of people.”

Save one: a vaccine skeptic who engaged Antwiwaa on safety concerns. Eventually, after a bit of back-and-forth, he got the shot.

“That made all the difference to me,” Antwiwaa said of agreeing to do the campaign.

This is what marketing firms like Denver-based The Idea Marketing, California-based Xomad and Chicago-based Res Publica Group want to see. They’re hired by health agencies to identify local influencers and coordinate messaging.

Xomad has developed a platform where influencers, content creators and health officials can rapidly fine-tune or change messaging to respond to events such as last spring’s pause in the use of Johnson & Johnson vaccines, new online misinformation or an expansion of age groups eligible for shots.

Rob Perry, Xomad’s CEO and founder, notes that a July study by the Knight Foundation and the city of San Jose found a direct correlation between a flurry of local influencer posts on Instagram and higher daily vaccination rates.

“Even in Silicon Valley they needed help reaching the immigrant, Black, Latino and Vietnamese communities,” Perry said. “No one’s bashing anti-vaxxers over the head. The last thing these trusted messengers want to do is polarize their followers. It’s their followers’ choice.”

Health officials say so-called “nano” and “micro” influencers, with fewer than 10,000 and 100,000 followers, respectively, are well-positioned to reach Generation Z and Millennials who get their news from social media.

The Oklahoma City County Health Department debuted the approach in late 2020, hiring Xomad to recruit local influencers to suggest ways their followers could celebrate stay-at-home holidays, agency spokeswoman Molly Fleming said. The campaign changed with the rollout of vaccines, and could change again with the advent of booster shots, as well as with non-COVID-19 issues such as a recent uptick in syphilis cases, she said.

One Oklahoma influencer is Pandora Marie, a 40-year-old street dancer and artist of Chicana, Chickasaw and Choctaw descent who has built a 30,000-strong Instagram following. She infuses her messaging with references to Native American culture and dance.

“When I started to share the COVID posts, I had people asking questions, which is always a good sign,” Marie said.

Fleming acknowledged it’s hard to measure how many vaccinations among 18- to 29-year-olds and minorities the strategy delivers.

But officials can see residents’ interactions with posts, “and when you’re spending public health dollars, that’s important,” she said. “If we pay for a billboard, we don’t know if you’ve seen it or if it changed your life at all.”

In Chicago, Cook County Health has worked with influencers such as McKinley Nelson, a young activist who uses basketball and entertainment to protect inner city youth from street violence. Its #MyShot campaign encourages 18- to 34-year-olds in Black and Hispanic communities to seek out vaccine information.

Soon to be called Life is Better Vaxxed, the campaign is one element in a multilayered communications strategy that includes vaccine information ads at gas stations and barber shops, and on coasters in bars, said Cook County Health spokeswoman Caryn Stancik.

“The mission, as it always has been for us, is equity,” Stancik said. “Our digital strategy targets individual neighborhoods and zip codes, and in these communities we layer in as many strategies as we can to help get people vaccinated and address misinformation.”

It appears to be helping, she said.

“I don’t want to say this alone will work,” Stancik said. “But people are coming to hundreds of pop-up local clinics based on digital word of mouth, so the information is resonating.”

Back in Rifle, Sgt. Cornejo built his Facebook following — way above the town’s roughly 9,700 residents — with videos largely centering on police work. He’ll strum his guitar and sing the occasional ballad, all of it endearing him to what he considers an extended family.

“I got COVID last year and shared that experience,” the 32-year-old said. “Is the vaccine going to protect you 100% of the time? No. But I compare it to wearing a seat belt — it doesn’t ensure nothing bad will happen, but your chances of saving your life are a lot higher.”

https://apnews.com/article/lifestyle-technology-joe-biden-social-media-business-a2992b2881fcef68e1144efa7b869844

Abbott announces COVID mitigation measures, asks hospitals postpone elective procedures

 Texas Gov. Greg Abbott (R) announced new COVID-19 mitigation measures on Monday, including asking hospitals to delay elective medical procedures and bringing in medical personnel from out-of-state.

In a press release, Abbott's office said the Texas Department of State Health Services (DSHS) will be bringing in out-of-state personnel to assist in operations as coronavirus cases surge across the nation, driven by the highly contagious delta variant.

Abbott also sent a letter to the Texas Hospital Association, asking that they voluntarily delay elective medical procedures that can be put off without detriment to patients in order to conserve hospital space.

According to the statement, Abbott has also asked DSHS and the Texas Division of Emergency Management (TDEM) to open more COVID-19 antibody infusion centers that can treat COVID-19 patients who don't need hospitalization.

"The Governor is also directing TDEM and DSHS to increase vaccination availability across the state and encourages all Texans to get the COVID-19 vaccine," the statement read.

"The State of Texas is taking action to combat the recent rise in COVID-19 cases and ensure that our hospitals and communities have the resources and support they need to mitigate the virus," Abbott said. "Texans can help bolster our efforts by getting vaccinated against COVID-19. The COVID-19 vaccine is safe and effective, and it is our best defense against this virus."

Texans may call 844-90-TEXAS or go to covidvaccine.texas.gov to arrange a vaccination or find a provider.

Abbott notably did not mention any action regarding masks. In May, he banned local governments and schools from issuing mask mandates.

Abbott and Florida Gov. Ron DeSantis (R) have faced increasing criticism over their mask mandate bans as delta variant cases rise among the unvaccinated.

According to the Johns Hopkins University COVID-19 tracker, Texas currently has seven-day moving average of over 13,000 coronavirus cases. The daily positivity rate in Texas is currently about 18 percent.

Roughly 46 percent of the state's population is fully vaccinated against COVID-19. Nearly 80 percent of hospital beds in the state are currently filled.

https://thehill.com/homenews/state-watch/567072-abbott-announces-covid-mitigation-measures-asks-hospitals-to-postpone

US to send additional vaccine doses to Mexico

 The United States will send additional COVID-19 vaccine doses to Mexico, the White House said Monday, after the Mexican government said it would ask for millions more shots to combat a surge in cases.

Vice President Kamala Harris spoke by phone with Mexican President Andrés Manuel López Obrador. The two leaders discussed the flow of migrants coming across the U.S.-Mexico border, as well as the pandemic, according to a readout of the call.

"President López Obrador thanked the United States for assistance in combating the COVID-19 epidemic, including over 4 million vaccines that have already been delivered. Vice President Harris was pleased to share the U.S. government is committed to sending additional doses of vaccine to Mexico," the White House said.

The White House did not specify how many doses it would send, but Bloomberg reported the U.S. would be shipping Moderna and AstraZeneca shots to Mexico. Moderna has yet to be approved for use in Mexico, but officials expect that to change soon, Bloomberg reported.

Mexico has had nearly 250,000 deaths attributed to COVID-19 since the start of the pandemic, one of the highest totals in the world. The nation is grappling with another surge in cases as it struggles to get its population vaccinated.

The U.S. had previously donated roughly 4 million vaccine doses to Mexico, including Johnson&Johnson and AstraZeneca shots.

In addition to the pandemic, Harris raised the issue of immigration during the call, the White House said, calling the border situation a "top priority" for the Biden administration.

https://thehill.com/policy/international/567075-us-to-send-additional-vaccine-doses-to-mexico

Antibody-drug conjugates advance into early therapy

 Much of the potential of Astrazeneca’s Enhertu and Roche’s Polivy lies in advancing these antibody-drug conjugates into therapy lines earlier than those cited on their current labels. This morning both appeared to score important victories in pivotal studies designed to achieve this.

Although Enhertu and Polivy target different diseases – breast cancer and lymphoma respectively – they have led parallel existences, winning accelerated US approvals in 2019 but posting modest sales so far. No data are available yet from the Destiny-Breast 03 and Polarix trials toplined today, but they will determine whether the sellside’s respective 2026 revenue expectations of $4.1bn and $1.4bn are achievable.

Two weeks ago Astra reported $89m of first-half sales from Enhertu, a Her2-directed ADC, in its first indication of third-line or later Her2-positive breast cancer. Accelerated approval was won in this setting based on the uncontrolled Destiny-Breast 01 study.

This morning’s success related to Destiny-Breast 03, a second-line breast cancer trial that is the first to compare Enhertu against active control – Roche’s rival ADC Kadcyla. Astra said a data-monitoring committee had recommended an interim halt owing to “significant and clinically meaningful” improvement in median PFS; OS was said to be immature but trending positively.

Full data are needed to quantify the meaningfulness of the survival benefit and the rates of interstitial lung disease, a black-boxed adverse event that could hinder earlier-line use. Possible venues for full results presentation include the Esmo and the San Antonio Breast Cancer meetings.

Still, Astra is wasting no time, and is running numerous breast cancer trials for Enhertu, including the front-line study Destiny-Breast 09, which got under way in the past three months. This is likely spurred by the large bet it made on Enhertu, licensed from Daiichi Sankyo for $1.35bn, and by mounting competition in Her2-positive breast cancer.

A tale of two antibody-drug conjugates
StudySettingDataRegulatory
Enhertu, Astrazeneca/Daiichi Sankyo (Her2+ve breast cancer)
Destiny-Breast 01Median 6 prior lines, incl Kadcyla60.9% ORR; 16.4mth mPFS; 13.6% interstitial lung diseaseAccelerated approval for ≥3L, Dec 2019
Destiny-Breast 032L (post Herceptin + taxane), vs KadcylaPositive for mPFS; OS immature but numerically positiveFiling H2 2021
Destiny-Breast 04≥2L, Her2-low, vs investigator's choice chemoPrimary endpoint: PFS by independent reviewFiling H1 2022
Destiny-Breast 023L, post-Kadcyla, vs Herceptin/Tyverb + chemoPrimary endpoint: PFS by independent reviewFiling H2 2022
Destiny-Breast 05Adjuvant, vs KadcylaPrimary endpoint: iDFSFiling 2022+
Destiny-Breast 061L, Her2-low, vs investigator's choice chemoPrimary endpoint: PFS by independent reviewFiling 2022+
Destiny-Breast 091L, +/-Perjeta, vs Herceptin + Perjeta + taxanePrimary endpoint: PFS by independent review
Polivy, Roche (diffuse large B-cell lymphoma)
GO29365≥3L, benda+Rituxan combo, vs benda+RituxanORR 40% vs 18%Accelerated approval Jun 2019
Polarix1L, Rituxan-CHP combo vs Rituxan-CHOPPositive for investigator-assessed mPFSData being shared with regulators
Source: clinicaltrials.gov & company information.

Indeed, only today Seagen shelled out $200m for rights to a little-known anti-Her2 ADC, disitamab vedotin/RC48-ADC, originated by the Chinese company Remegen. However, breast cancer is not its primary focus; rather, disitamab has US breakthrough therapy designation for Her2-positive urothelial cancer, where data were presented two years ago.

Investors might well ask what the deal says about the faith Seagen has in its own Tukysa, a small molecule approved for second-line Her2-positive breast cancer in combination with Herceptin.

Lymphoma first?

For its part Roche is trying to position Polivy, an anti-CD79B ADC, as the first therapy in two decades to improve PFS in front-line diffuse large B-cell lymphoma, a claim it says is backed by the outcome of the Polarix trial toplined today.

Polivy is approved in combination with bendamustine and Rituxan for third-line or later DLBCL, a setting in which first-half 2021 sales came in at $103m. Polarix tested it front line on top of Rituxan plus CHP chemo, a regimen said to have beaten Rituxan plus CHOP chemo in terms of investigator-assessed mPFS.

DLBCL patients have not seen many treatment advances beyond the approvals of Car-T therapies in relapsed/refractory settings, and of Morphosys/Incyte’s anti-CD19 MAb Monjuvi for second-line use. Still, Jefferies analysts are sceptical that the benefit in Polarix will be enough to justify wholesale switching from Rituxan-CHOP; full Polarix data, possible at Ash in December, will reveal all.

Either way, it is clear that after years of misfires ADC-based drugs are making strides at last. And Seagen appears to have its finger in many pies in this small world: its technology lies behind Polivy, for instance, and the US company had a deal with Daiichi that is now the subject of a legal claim over Enhertu.

Why Seagen, an ADC expert, has had to go externally to Remegen to bring in an asset it might have been expected to develop itself is a question some investors might now be asking.

https://www.evaluate.com/vantage/articles/news/trial-results/antibody-drug-conjugates-advance-early-therapy

Bluebird exits Europe as another hold hits

 Bluebird Bio only recently resolved the clinical hold for Lentiglobin. Now it has been hit with another safety scare, this time with its other lentiviral vector-based gene therapy, Lenti-D. The company was quick to dismiss fears of a read-across to Lentiglobin, but similarities between the holds could give investors pause.

And that was not the only bad news dropped today during the group’s second-quarter earnings: Bluebird confirmed plans to wind down its operations in Europe after failing to strike deals with payers there. The company is still on track to split into separate gene therapy and oncology businesses in the fourth quarter, but the rationale for doing so now looks even shakier than before.

Bluebird opened down 23% today, and its market cap now sits at $1.3bn, not far off cash.

Second hold

Bluebird’s previous hold, for Lentiglobin, came after two cases of cancer – acute myeloid leukaemia and myelodysplastic syndrome – were reported in the project’s sickle cell disease trial (Bluebird split looks premature, February 16, 2021).

The group later ruled out its lentiviral vector as the cause of the AML, and concluded that the case of MDS was, in fact, transfusion-dependent anaemia. The hold was lifted in June.

The latest hold came after a patient developed MDS around a year after being treated with Lenti-D in the phase 3 ALD-104 study in cerebral adrenoleukodystrophy (CALD). This time, Bluebird has already concluded that the case was likely mediated by the lentiviral vector used in Lenti-D.

But the group still hopes to gain approval of Lenti-D based on the current dataset, saying the risk/benefit profile of the project remains favourable given the “devastating consequences” of CALD and the shortcomings of the current standard of care, allogeneic stem cell transplant.

Bluebird plans to complete its rolling BLA by the end of 2021. Lenti-D recently got the go-ahead in Europe, where it is branded Skysona, although presumably the group will not be selling it there given today’s announcement.

Expectations are low for Lenti-D, with the sellside only forecasting $97m sales by 2026, according to Evaluate Pharma's consensus. Around a quarter of these sales had been expected to come in Europe.

No readthrough?

The bigger prospect at present is Lentiglobin, which is expected to bring in $723m the same year – although this figure has fallen from $1.5bn before Bluebird’s first clinical hold. The gene therapy is branded Zynteglo in Europe, where it has long had a hard time gaining reimbursement, so perhaps Bluebird's move to exit the continent is not entirely surprising.

The company believes that Lentiglobin still has a future in the US and is adamant that the latest hold has no implications for that gene therapy. During today’s second-quarter call executives pointed out the differences between the two therapies: Lenti-D employs a promoter call MNDU3, which leads to broad tissue expression and high levels of expression across all cell types, while Lentiglobin uses the BB305 vector, designed for specific expression only in cells that could become red blood cells.

Bluebird added that no other lentiviral vector haematopoietic stem cell gene therapies used the MNDU3 promoter, something that should be good news for others in the space.

Still, the latest news will only increase nervousness around the use of lentiviral vector-based gene therapies, which will be the lynchpin of Bluebird’s business once its oncology arm is spun off to become 2seventy bio.

Perhaps Bluebird would be better off cutting its losses in rare diseases and focusing on cancer, without the distraction of a spin-off.

https://www.evaluate.com/vantage/articles/news/policy-and-regulation/bluebird-exits-europe-another-hold-hits