AstraZeneca Plc and Amgen Inc said on Friday the U.S. Food and Drug Administration had granted a breakthrough therapy label for their drug to treat a type of severe asthma, potentially speeding up its development and regulatory review.
The drug, tezepelumab, is an injectable treatment that is expected to help a wider range of patients than existing asthma medicines like GlaxoSmithKline Nucala.
A breakthrough therapy status is designed to expedite the development and regulatory review of medicines that are intended to treat a serious condition and that have shown encouraging early clinical results.
A mid-stage trial in 2017 of 584 patients showed that tezepelumab reduced the annual rate of serious asthma attacks, known as exacerbations, by between 61 percent and 71 percent, depending on dose.
Tezepelumab is currently in late-stage trials.
The drug has shown promise in treating “a broad population of patients with severe asthma, including those ineligible for currently approved biologic therapies,” said David Reese, executive vice president of Research and Development at U.S.-based Amgen.
CRISPR pioneer Jennifer Doudna has set up shop in San Francisco’s Gladstone Institutes. Doudna, a UC Berkeley professor credited with the co-discovery of CRISPR-Cas9 genome editing technique, will focus on the development of new ways to implement the gene-editing technique for disease treatment.
Doudna, who is also an investigator with the Howard Hughes Medical Institute, has been named a senior investigator at Gladstone, a non-profit biomedical research organization. In her new role, Doudna will operate a lab focused on using CRISPR to study molecular mechanisms of disease and then “establish first-of-their-kind genome surgery approaches to treat disease by cutting out or modifying harmful DNA,” Gladstone News reported on Wednesday.
Doudna said Gladstone’s “agile environment” will help provide her and fellow researchers with the opportunities to delve into new research. At Gladstone, Doudna will work with Katherine Pollard, who heads the Gladstone Institute of Data Science and Biotechnology. Doudna will continue to focus on the immune system and help shape the “evolution of Gladstone’s long-standing effort in virology and immunology,” Gladstone News said. When Doudna and her team begin their work at Gladstone, they will initially begin research into developing novel curative treatments for genetic disorders. They will begin with neurodegenerative disorders and diseases of the eye, Gladstone News said. Additionally, Doudna and her team will use CRISPR technology to gain a better understanding of the genetics of some cancers, such as glioblastoma, the organization reported. The goal of that understanding will be the development of new targets for potential gene therapies for those indications. For glioblastoma and other brain diseases, Doudna is hoping to discover the most effective way to deliver those gene-editing molecules to the brain in order to treat the disease.
“CRISPR” refers to Clustered Regularly Interspaced Short Palindromic Repeats that occur in the genome of certain bacteria, from which the system was discovered. Cas9 is a CRISPR-associated endonuclease (an enzyme) known to act as the “molecular scissors” that cut and edit, or correct, disease-associated DNA in a cell. Gene therapy essentially transforms cells inside a patient to harness their immune system to fight an invading disease on its own. Initial work on CRISPR was done by Doudna and Emmanuelle Charpentier. Doudna’s groundwork laid the foundation for companies specializing in CRISPR technology to spring up, including Intellia Therapeutics, Caribou Biosciences and Swiss-based CRISPR Therapeutics. Those two companies licensed the CRISPR technology from the University of California. Other CRISPR-based companies have licensed the technology from the Broad Institute, including Editas Medicine, GE Healthcare, Monsanto and Evotec.
Doudna said her ultimate goal for genome surgery is that it will become the norm in treating patients. Gladstone News said Doudna “imagines a day when a patient with a genetic condition will visit a doctor, who will have access to a standard of care that involves genome editing as a treatment.” But, Doudna admitted that’s a “tall order.” Doudna noted there are some obstacles in the way of achieving that goal.
One obstacle could be public trust of the CRISPR therapies. In July, a new study was released that the gene-editing technique could cause “extensive mutations and genetic damage.” The study published in NatureBiotechnology said CRISPR can cause cellular damage that is too difficult to discern by standard DNA tests. The study showed that researchers using CRISPR deleted thousands of DNA bases – some of them that were not close to the spot of the initial edit. That was concerning, the study said, because some of the deletions can silence genes that are supposed to be active, while activating some genes that could potentially cause disease, like cancer.
Opko Health provided a comment on the lawsuit filed by the SEC earlier today. It reads: “OPKO learned today that the Securities and Exchange Commission has filed a lawsuit in the Southern District of New York against a number of individuals and entities, including OPKO and its CEO and Chairman Phillip Frost. The SEC failed to provide notice of its intent to sue prior to filing the complaint, which contains serious factual inaccuracies. Had the SEC followed its own standard procedures, OPKO and Dr. Frost would gladly have provided information that would have answered a number of the SEC’s apparent questions, and filing of this lawsuit against them could have been avoided. OPKO and Dr. Frost have always prided themselves on adhering to the highest standards of financial disclosure, and they are confident that once a proper investigation is completed and the facts of the case have been fully disclosed, the matter will be resolved favorably for them.” The company added that the complaint does not contain any allegations about Opko’s financial practices, financial statements or business practices. The stock closed the trading day down 18%, or $1.01, to $4.58.
A mandatory pay model aimed at reducing Medicare spending on joint replacement surgeries was able to save money in its first year. The CMS in recent years has scaled back and canceled mandatory models.
Under the Comprehensive Care for Joint Replacement program, average total payments decreased by 3.9% or $1,127 compared to hospitals not participating in the model, according to federal data released Wednesday. At the same time, researchers observed no statistically significant changes in the quality of care as measured by readmission rates, emergency department visits, and deaths.
The program gives hospitals a fixed payment for all services related to joint replacement surgeries from admission to 90 days after the procedure, with no additional payments for complications, readmissions or post-acute services.
“Possibly the most notable outcome during the first CJR model performance year was that statistically significant changes in utilization and payments occurred so quickly,” the report said.
The study analyzed results from 731 CJR participant hospitals and 841 hospitals not in the experiment, which lasted from April 1 to Dec. 31, 2016.
Last year, the CMS scaled back the CJR program citing the burden of the program and the belief that models should be largely voluntary. The CJR model is now only mandatory in 34 geographic areas compared to 67 geographic areas when it first launched.
The agency estimates that 465 hospitals are participating in the effort. That figure is down from 800 acute-care hospitals that were expected to participate in the program.
After interviewing hospital staff, researchers said there may not have been a change in the practice of medicine at these facilities had the experiment not been mandatory.
“These findings suggest that a mandatory model may impel action across a broad range of hospitals that may not otherwise have acted to reduce episode payments,” the report said.
Proponents of value-based care hope the results will encourage the CMS to reconsider the use of mandatory models. Many of the hospitals in CJR are ones that chose to skip other pay models such as the Bundled Payments for Care Improvement Initiative, according to Andrew Ryan, an associate professor in the department of health management and policy at the University of Michigan’s School of Public Health.
Among the 30,000 attendees of the Rutherford Street Fair, sweating it out on the street between the zeppoles and deep-fried Oreos, was the pharmaceutical millionaire who wants to be their next senator.
Bob Hugin, the former CEO of Celgene, spent Labor Day walking through the crowd with a phalanx of staff and volunteers, each with a sign and a T-shirt bearing his name. They chanted, cheered, and sloganeered as Hugin’s would-be constituents looked on, varyingly bemused or befuddled at the merry little militia demonstrating in their town. Hugin shook hands, posed for photos, and remembered to say “good to see you” but never “nice to meet you.”
This is his life now. In February, the 64-year-old left behind the air-conditioned conference halls, sycophantic analysts, and princely pay packages that come with being a Fortune 500 CEO. He branded himself “a different kind of Republican,” set aside $20 million of his own money, and became the GOP’s only hope to unseat the incumbent Sen. Bob Menendez.
“To be honest with you, I wouldn’t be running if it wasn’t for him, because he’s wrong for New Jersey, and he’s wrong for our country,” Hugin said in the shadow of his hulking tour bus, painted to blare his name and his campaign’s bellicose slogan: “Send in a Marine.”
Hugin might seem a strange choice. He has never before held office, and his industry, pharma, has an approval rating of just 33 percent, according to Gallup. The rising cost of prescription drugs, virtually the only issue that united President Trump and Hillary Clinton, is something with which he has experience.
Revlimid, Celgene’s banner cancer drug, costs nearly twice as much today as it did in 2010, the result of repeated price increases. On the eve of Hugin’s retirement, Celgene paid $280 million to settle charges that it defrauded Medicare to boost profits.
At a time of widespread foment over drug prices, can a pharma CEO get elected to the U.S. Senate?
“Look, Bob Hugin has $20 million that he’s willing to spend on this race, so he absolutely has a shot,” said Matthew Hale, a political science professor at Seton Hall University in South Orange. “I think it’s quite likely that he’s going to spend $20 million and lose, but you can’t discount that kind of money.”
Hugin’s wealth has turned the New Jersey Senate race into a surprisingly tight and immediately vicious campaign, one that doubles as a referendum on the drug industry’s place in the American psyche. While Hugin runs as a business leader devoted to winning a war on cancer, Menendez insists he’s a pantomime villain of pharmaceutical greed.
But Menendez has his own issues. He’s less than a year removed from an embarrassing corruption trial that ended in a hung jury. In his most recent primary, he ceded 37 percent of the vote to an unknown candidate who spent zero dollars campaigning.
The latest poll, conducted in mid-August, had Menendez leading Hugin by just six points. Soon it’ll be up to the voters.
Hugin, the former CEO of Celgene, at the Rutherford Street Fair.MARIA GIANOPOLOUS/BOB HUGIN FOR SENATE CAMPAIGN
Since winning the Republican primary in June, Hugin has embarked on what the campaign is calling “the Better Bob Bus Tour,” which has taken the candidate to a Kenny Chesney concert at the Meadowlands, the Asian American Retailers Association trade show in Edison, and the Ecuadorian Parade and Festival in Newark, where the former CEO sipped from a sliced-open pineapple while wearing a sash that read, in all caps, “INVITADO.”
Walking through Rutherford, Hugin had largely settled into the uncanny valley of a politician on the trail. He shook hands and gave thumbs up, ending his clipped conversations with a fist jab that called to mind Tiger Woods after sinking a putt. There were awkward moments, like when a passerby confused the staff’s chants of “Hugin” for “union,” or when a bystander picked up one of the campaign’s brochures and then promptly handed it back.
By the end, Hugin was doused in sweat that his sky-blue polo did little to conceal as he ate a celebratory hot dog from the volunteer firefighters’ booth. It was, after all, 97 degrees, and nearly everyone was drenched.
But not Menendez. The 64-year-old senator, who won his first election when he was 20, made an identical sojourn up and down Park Avenue and emerged, after 90 minutes in the sun, with neither a visible droplet nor a hair out of place.
He beamed at every child, met every joke with a big laugh, and comfortably hit his angles for every selfie. His walk through the street fair was consistently interrupted by hugs from well-wishers, backslaps from down-ticket Democrats, applause from vendors, and shouts of “Hey, Bobby!” and “Good luck, Bob!” He ended his walk in the shade, trading jokes with freeholders and a county executive as a distant cover band played “Daydream Believer” from a gazebo.
Where Hugin was greeted like new management, Menendez was plainly at home.
“Nobody knows who this guy is,” said Patrick Murray, director of the Monmouth University Polling Institute, referring to Hugin. “You’ve got to understand New Jersey politics: Unless you’re already a statewide elected official, you’re just not known to the electorate.”
Even if that changes, Hugin might not benefit. In national polls, concern about the cost of health care is the No. 1 issue among voters, Murray said. That, combined with the general distaste for pharma, could be damning for the former Celgene CEO.
Hugin defends the price hikes to Revlimid by pointing out that the drug has proven to benefit more patients than first thought, which means it’s more valuable and thus ought to be more expensive.
“The thing I think people don’t realize over time is that more than 90 percent of the patients that ever took a Celgene cancer drug paid $50 or less per month in copay,” Hugin told STAT. “And the company invested more than 40 percent of its revenue into R&D, because it’s not good enough where we are in cancer, even though we’ve made good strides.”
Whether that will assuage voters with broad-based anxiety about the cost of health care remains to be seen. But that’s where the ex-CEO’s $20 million comes in. Hugin has been attacking Menendez since April, paying for TV ads before he’d even won his primary. The message has been consistent: The charges against Menendez, which prosecutors dropped earlier this year, have disgraced the senator and his state, and the time has come for change.
Among New Jerseyans at the Rutherford Street Fair, it seems to have resonated.
John Tavaska, a retiree from Passaic, voted against Menendez in the Democratic primary and laments that “we have a candidate with such” — and here he pauses — “baggage.” The Menendez saga, which began in 2015 and resulted in a public letter of admonition from a bipartisan Senate committee, could give Hugin a chance.
“I think it’ll be close, closer than anyone thought,” said Tavaska, who plans to back Menendez in November.
Christine Beidel, a Democrat from Rutherford, said the charges against Menendez left “a little black mark next to his name.” She voted for the senator’s primary challenger in June, but, like Tavaska, will support him in the general election, as the idea of electing a man with a record of “gouging people for lifesaving drugs” is too much to bear, she said.
“People are more interested in talking about Menendez,” Beidel said, “and that stuff hasn’t been proven. I mean, sure, it’s probably true, but this” — Celgene’s raising of drug prices — “is true. We know he did it.”
Hugin’s televisual blitz explains why the race has tightened in recent months, Murray said, but it comes with a caveat. The latest poll came before Menendez ran a TV ad of his own, one that takes Hugin to task over the price of Revlimid.
“Corporate greed looks like drug company CEO Bob Hugin,” the ad begins, before pointing to Revlimid’s escalating price and noting, curiously, that the drug is cheaper in Russia than it is in the U.S.
“The way Menendez is beginning to define Bob Hugin is as the guy who raised prices on cancer patients,” Murray said. “Then, down the line, you’ll see ads saying, ‘Oh, by the way, he gave $200,000 to Donald Trump. And then the message is he stole money from cancer patients to give to Donald Trump, and that’s a powerful one-two punch in New Jersey.”
Hugin, like most centrist Republicans, has a complicated relationship with the president. In 2016, he gave the maximum $5,200 to Trump’s campaign and donated another $233,000 to the Republican National Committee. But on the policy side, Hugin has proclaimed himself to be pro-choice, in favor of marriage equality, and supportive of a path to citizenship for undocumented immigrants.
And yet with each public appearance, Hugin has passed on the opportunity to court undecided voters by openly criticizing Trump, whose New Jersey approval rating hovers in the 30s.
In the days following the death of Sen. John McCain, Hugin punted on a question about the president’s yearslong feud with the Arizona Republican, which famously began with Trump denigrating McCain’s military service. Hugin didn’t defend the president but instead pleaded ignorance.
“I would have no reservation of criticizing anybody if they did anything to disrespect Sen. McCain,” Hugin said, according to Politico. “I’m just not knowledgeable of the facts.”
Menendez, predictably, pounced.
“To say you didn’t know that was happening? Come on,” he told reporters at a press conference. “It’s because you don’t want to criticize President Trump.”
Trump’s unpopularity has forced Hugin onto a tightrope he’ll have to walk until Election Day, said John Weingart, associate director of the Eagleton Institute of Politics at Rutgers University. If he embraces the president, he’ll alienate centrist independents who are less than thrilled with Menendez. But if he denounces Trump, voters in the Republican strongholds of South Jersey might decide to stay home. And then there’s the fact that, no matter Hugin’s views on Trump, a vote for him is a vote to further empower Republicans in the Senate.
New Jersey hasn’t sent a Republican to the Senate since 1972.
“It’s hard to imagine that New Jersey voters who have voted overwhelmingly Democratic for president since Bill Clinton would turn to picking a senator who would support Mitch McConnell for Senate leadership rather than Chuck Schumer,” Weingart said.
Back in Rutherford, the two Bobs’ squabble played out in miniature. Hugin’s campaign handed out hard copies of a Senate ethics committee letter admonishing Menendez for his actions during the bribery scandal, while the senator’s volunteers passed around printouts of a Department of Justice press release announcing Celgene’s $280 million settlement payment.
And, Hugin, just 20 miles away from Celgene’s headquarters in Summit, was wrapping up his latest public appearance as a political candidate. After posing for photos with staff and volunteers, he made a final rah-rah pitch.
“Nov. 6, if we get the vote out, we’re going to win,” Hugin said to applause from his small contingent. “New Jersey deserves better.”
GlaxoSmithKline said on Friday that U.S. health authorities had asked for more information about its Nucala drug for use in combating chronic obstructive pulmonary disease (COPD).
GSK said it had received a complete response letter (CRL) from the U.S. Food and Drug Administration (FDA) regarding its application for mepolizumab – the generic name for Nucala – as an add-on treatment to inhaled corticosteroid-based maintenance treatment.
“The CRL states that more clinical data are required to support an approval,” the company said in a statement. “GSK will work closely with the FDA to determine the appropriate next steps for the supplementary biologics licence application.”
The FDA has previously cleared Nucala to treat severe asthma.
Prazosin (multiple brands), an alpha-adrenergic blocker used to treat high blood pressure, anxiety, and posttraumatic stress disorder (PTSD), may also be effective in the treatment of alcohol use disorder (AUD), results of a small, randomized controlled trial suggest.
Investigators found that prazosin may reduce the likelihood of heavy drinking and the number of drinks per week over time but not the number of drinking days per week. This suggests that prazosin may be most useful as a “harm reduction” pharmacologic treatment that leads to safer drinking habits rather than full abstinence, the investigators note.
“We believe our finding that prazosin has efficacy with regard to reducing heavy drinking indicates that the alcohol pharmacologic treatment field needs a paradigm shift in how addiction is conceptualized,” first author Tracy Simpson, PhD, told Medscape Medical News.
“Specifically, we think this finding strongly suggests that norepinephrine systems in the brain are important for initiating and maintaining addiction and that this is a promising area for additional basic and clinical science research seeking to optimize [AUD] treatment efficacy,” said Simpson, from the VA Puget Sound Health Care System and the Department of Psychiatry and Behavioral Sciences, University of Washington, in Seattle.
The study was published online August 29 in the American Journal of Psychiatry.
Harm-Reduction Agent?
The 12-week double-blind trial included 92 adults who had AUD but not PTSD. The patients were randomly allocated to receive either prazosin or placebo. During the first 2 weeks, the medication was titrated to a dosing schedule of 4 mg in the morning, 4 mg in the afternoon, and 8 mg at bedtime. Eighty of the participants completed the titration period and were included in the primary analyses (40 in each arm).
There was a significant interaction between condition and week for both number of drinks and number of heavy drinking days, such that the rate of drinking and the probability of heavy drinking showed a greater decrease over time for those taking prazosin relative to those taking placebo, the researchers report.
However, at week 12, the two groups did not differ with respect to the number of heavy drinking days (1.0 days for the prazosin group and 1.2 days for the placebo group) and the number of drinks per week (13.3 with prazosin and 13.1 with placebo). And prazosin did not reduce the number of drinking days over time.
Average alcohol craving decreased over time in both the prazosin and the placebo groups, and there was no difference between groups in change in craving over time.
Systolic blood pressure decreased in the prazosin group by a mean of 3.5 mmHg across the 12-week study period but increased in the placebo group by a mean of 3.1 mmHg.
Notably, participants in the prazosin group were significantly more likely to report drowsiness and edema. In addition to the 12 participants who did not continue treatment past the titration phase (eight in the prazosin group and four in the placebo group), four individuals in the prazosin group (vs none in the placebo group) opted midway through the study to discontinue study medication and continue on an intent-to-treat basis. These patients completed daily calls, study visits, and assessments and were included in the primary analyses.
The researchers say their findings provide “preliminary support” for an effect of prazosin on heavy drinking and number of drinks per week, but they say that replication of their findings by other research groups is warranted. They also say further research is needed to establish optimal dosing regimens and to evaluate which subgroups may derive the most benefit from prazosin for AUD.
No Better Than Placebo?
Experts who reviewed the study for Medscape Medical News urged caution in drawing any firm conclusions from this study.
Claire Wilcox, MD, from the MIND Research Network and the University of New Mexico in Albuquerque, noted that prazosin “wasn’t that well tolerated” and doxazosin (Cardura, Pfizer), a medication that has a similar mechanism of action but that is administered only once daily, might end up being a better, more tolerable medication for AUD than prazosin.
Tim Brennan, MD, MPH, director, Addiction Institute, Mount Sinai West and St. Luke’s, and director, Fellowship in Addiction Medicine Program, Icahn School of Medicine at Mount Sinai, New York City, said this study “does not prove that prazosin is any more efficacious than placebo.”
He noted that there were “similar decreases in percent days drinking, percent heavy drinking days, average drinks per day, and average drinks per drinking day between the prazosin group and the placebo group. Simply stated, the placebo seems to have worked just as well as the prazosin for these outcomes,” said Brennan.
“Regarding the days of heavy drinking decreasing more rapidly in the prazosin group compared to the placebo group, I don’t think it really matters much as long as both groups end up in the same place, which they do,” said Brennan. “More research is needed, with larger sample sizes, before prazosin should be recommended for treatment of alcohol use disorder,” he concluded.
The study was supported by the National Institute on Alcohol Abuse and Alcoholism. Dr Simpson, Dr Wilcox, and Dr Brennan have disclosed no relevant financial relationships.
Am J Psychiatry. Published online August 29, 2018. Abstract
