With new results, Sarepta's 2nd gene therapy holds steady

 

• Sarepta said its gene therapy for a rare genetic disease known as Limb-girdle muscular dystrophy continued to help patients two years after a single treatment, with trial participants sustaining functional gains and producing a protein that protects muscle tissue from damage.
• The data, released at the Muscular Dystrophy Association's scientific meeting Thursday, included an update for three patients given a low dose of the treatment two years ago and three more who are a year removed from receiving a higher dose. The high-dose group also showed functional gains after one year, although SVB Leerink analyst Joseph Schwartz noted that result fell short what was seen in low-dose recipients at the same time point.
• The data, which compared Sarepta's treatment to historical controls, not a placebo, could help reassure investors in Sarepta's broader gene therapy platform after its lead project, the experimental Duchenne muscular dystrophy treatment SRP-9001, missed its main goal in a mid-stage trial in January. Sarepta's shares have lost roughly half their value since.
• Sarepta has three marketed products treating Duchenne, plus a beefy pipeline of 39 experimental RNA-based programs and genetic medicines for rare diseases. One towers above them all, however: SRP-9001. Its clinical trial setback in January cut the company's valuation in half as a rival treatment from Pfizer appeared to be taking a lead.

With the path to market looking longer for SRP-9001, other pipeline projects may figure more prominently in Sarepta's outlook, and the data from the follow-up project, known as SRP-9003, may be reassuring to investors.

SRP-9003 treats a type of muscular dystrophy called Limb-girdle that particularly affects the arms and legs. To do so, it helps replenish the deficiency of a protein called beta-sarcoglycan, the lack of which is thought to trigger the disease.

The first three patients in Sarepta's early-stage trial were infused with a low dose of the gene therapy, and after 18 months of treatment had improved their score by 5.7 points on a 20-item test that measures their ability to do such tasks as stand up from a chair or stand briefly on one foot. That improvement was sustained at two years, Sarepta reported Thursday.

In a research note, SVB Leerink's Schwartz wrote that untreated patients would have been expected to decline by 4.6 points over the same time period. Biological measures, such as expression of the beta-sarcoglycan protein, also showed positive signs, although they were short of expression seen in the healthy population.

Three higher-dose patients also showed improvements at one year. Their four-point increase on the functional test was short of the six points seen in the lower-dose group at 12 months, although Schwartz noted that biomarkers indicated the high-dose group may have been less disabled when they received the gene therapy.

The company hasn't seen any new safety signals. One adverse event was reported in an earlier data release, a patient who was dehydrated from vomiting.

Schwartz wrote that the data could set the stage for a study that could be submitted to regulators to support approval. There are no treatments for limb-girdle muscular dystrophy, so a regulatory pathway will need to be discussed with the Food and Drug Administration, as well as a quality assessment of the batch of gene therapy to be used in that trial. That could make the path forward for limb-girdle gene therapy different than the one Sarepta's traversing in Duchenne, where there are at least some marketed drugs for the condition.

The next study should begin this year, Schwartz wrote.

https://www.biopharmadive.com/news/sarepta-limb-girdle-muscular-dystrophy-gene-therapy-positive-data-2-year/597047/

Losing Dollars By Pinching Pennies: When Short-Termism Goes Bad

 This time a year ago, Navin Katyal's phone wouldn't stop ringing.

The head of Pfizer's North American hospital unit, which sells 165 different medications like antibiotics, analgesics and sedatives for patients on ventilators, was receiving the same message from his thousands of customers as Covid-19 spread: We need more medicine, and we need it now. "Unprecedented demand all at once," he said to me this week. To respond properly to the crisis, Pfizer had to crank up production but also determine whose requirements were most urgent. "Just as with products like toilet paper, we had to sort out who was using the drugs and who was stocking up," he said.

Pfizer is hardly the only company to be forced to figure it out on the fly: The Wall Street Journal reported earlier this week that supply chain woes have mounted world-wide for all sorts of businesses, thanks to the pandemic and other disruptions. The world is learning that a just-in-time inventory system and a short-term focus on maximizing return on investment is no match for a restive Mother Nature.

Mr. Katyal's unit sells items that carry low profit margins, but no one doubts their importance after the pandemic. The emergency ramp-up of those products was a success: It was able to quadruple normal production rates of nine drugs that were in especially high demand. But for its customers, it was too late to avoid the damage. No stockpiles of essential medicines or personal protective equipment for medical staff made the early stages of the pandemic deadlier and more disruptive than it otherwise might have been.

If the extra deaths weren't bad enough, the situation also wreaked financial havoc for hospitals, which further impacted patient care. Suddenly, elective surgeries like hip replacements were too risky to perform for many hospitals, and a key profit center was lost. Medical equipment with seven-figure price tags was mothballed for want of small-ticket items like masks, gloves and gowns.

If only public health disruptions were the only sort that businesses have to worry about. Severe winter weather in Texas last month froze generators' water intake facilities and knocked out power for days, snarling local economic activity in the process. Utilities were caught off guard by the weather, even though such extremes aren't entirely new. In a business world where maximizing return on investment has long been the highest priority, corporate America has a way of costing itself big by not adequately preparing for trouble.

So why do similar mistakes keep playing out? In the case of Texas, strategist Michele Wucker points out that the massive financial losses are distributed among homeowners, renters and businesses that need a reliable grid to function. Those entities didn't have a say in whether equipment should be winterized. "Businesses are basically being subsidized for taking unwise risk when the consequences of bad decisions fall mainly on customers and taxpayers," said Ms. Wucker, author of the new book You Are What You Risk: The New Art and Science of Navigating an Uncertain World. The end result, she told me this week, is that the benefits of risk taking are privatized, while the consequences of bad decisions can be socialized. The short-termism that Wall Street often demands of CEOs certainly doesn't help.

While that explanation is clear, its implications are worrying: after all, bad incentives are much more difficult to fix than they are to identify.

As for hospital shortages, things aren't as simple as executives failing to prepare for trouble, explains Mr. Katyal. After all, they have significant cost pressures of their own. Bulk contracting can help hospitals use collective buying power to bring down expenses, but that has a downside: A 2019 report from the Food and Drug Administration highlighted a lack of financial incentives to maximize production of certain drugs, coupled with contracts that could reset prices for manufacturers without warning. "Contracts should ensure that manufacturers earn sustainable...returns on their investment in launching or continuing to market prescription drugs, especially older generic drugs that remain important elements of the medical armamentarium."

Clearly, there is value in fixing the next societal pressure point before it bursts, not after. At least some management teams are wide awake. For instance, scientists at Genentech and parent company Roche are working to develop new classes of antibiotics to keep up with the growing threat of antibiotic resistance. "So much of our practice of modern medicine requires good infection control," explained Genentech vice president and staff scientist Man-Wah Tan; basic dental procedures and routine surgeries could eventually become too dangerous to perform were the problem left unchecked.

Discovering new antibiotics isn't the only hurdle: Figuring out how to incentivize more development is also a challenge. After all, a new antibiotic that can tackle drug-resistant infection should be used sparingly in order to preserve its useful life, according to John Young, head of global infectious disease research at Roche, making it a challenge to sell.

Away from healthcare, companies like 3M are focused on rebuilding confidence in the return to work and play. After quadrupling production of its N95 respirators last year, 3M now expects increased demand for hygiene monitoring systems for food service areas and a protective film it makes for handrails, among other products, said Chief Technology Officer John Banovetz.

Anticipating what's coming next has always been a good way for companies to turn a profit. But in less turbulent times, executives have often been rewarded for pinching pennies instead.

Over the past year it's become clear that pinching too hard can cost them, and their customers, dollars.

https://www.marketscreener.com/quote/stock/PFIZER-INC-23365019/news/Losing-Dollars-By-Pinching-Pennies-nbsp-When-Short-Termism-Goes-Bad-32740017/

Scott Gottlieb On Heated Exchange Between Anthony Fauci And Rand Paul

 Former FDA Commissioner Dr. Scott Gottlieb commented on the heated mask debate between Chief Medical Advisor to the President Dr. Anthony Fauci and Republican Sen. Rand Paul, noting "both made valid points."

What Paul Argues: During a U.S. Senate hearing on Thursday, Paul accused Fauci of parading "around in two masks for show." The Republican Senator from Kentucky argued multiple scientific studies conclude the odds of someone who is fully vaccinated or has fully recovered from a COVID-19 infection catching the virus again is "virtually" zero.

Fauci himself is fully vaccinated.

"There's virtually 0% chance you're going to get it and you're telling people that have had the vaccine who have immunity — you're defying everything we know about immunity by telling people to wear masks who have been vaccinated," CNBC quoted Paul as saying.

Paul further notes that continued mask mandates even after vaccination are contributing to vaccine skepticism.

"You want people to get the vaccine? Give them a reward, instead of telling them that the nanny state's going to be there for three more years and you've got to wear a mask forever. People don't want to hear it, and there's no science behind it," he said.

Fauci's Argument: Fauci said that masks are required because of the emergence of new variants that are known to evade some of the vaccines, particularly the one manufactured by Johnson & Johnson JNJ 0.37%.

"In the South African study conducted by [Johnson & Johnson], they found that people who were infected with wild type and were exposed to the variant in South Africa, the 351, it was as if they had never been infected before, they had no protection," Fauci said.

The CDC said in revised guidelines in March that fully vaccinated individuals can safely meet with others indoors without masks or social distancing. The guidelines also note that fully vaccinated individuals (with few exceptions) who are potentially exposed to the virus do not need to be isolated unless they start to show symptoms.

Gottlieb: April And May Will Look Different: By many measures, March was supposed to be a "difficult month" but as the vaccine campaign continues uninterrupted, April and May will "look much more clear."

Within a few weeks, it could be "obvious" that masks may be safely removed, Gottlieb, a Pfizer Inc. PFE 0.7% and Illumina, Inc. ILMN 1.64% board member said.

"Right now it is not quite as obvious," he said.

Regardless, people will choose if they want to wear a mask or not, particularly in indoor settings.

'Not Worried' About U.K. Variant: The B.1.1.7 variant, commonly referred to as the U.K. variant, is not contributing to a surge of infection despite its status as a variant of concern, Gottlieb said.

"You are not seeing a sharp uptick like we expected which is an indication that the prior immunity that we have combined with vaccination is enough to quell B.1.1.7," he said.

The new variant called B.1.526 discovered in New York is a "cause of concern" while an uptick in Michigan might be a function of slower vaccination progress, he said.

Looking forward to the post-summer months, it is possible that the virus' momentum picks up again and some of the mitigation initiatives removed in the summer months could be put back into place.

https://www.benzinga.com/general/health-care/21/03/20255074/what-scott-gottlieb-thinks-about-the-heated-exchange-between-anthony-fauci-and-rand-paul

Enzo Biochem Blasts Higher as Revenue Jumps

 Enzo Biochem  (ENZ) - Get Report shares jumped Tuesday after the biosciences and diagnostics company reported a 62% surge in revenue for its fiscal 2021 second quarter, ended Jan. 31, as the COVID pandemic continued to drive demand for Enzo's testing equipment.

Revenue registered $31.5 million, up from $19.4 million last year. Enzo posted a profit of $2.3 million, or 5 cents a share, swinging from a year-ago loss of $7.7 million, or 16 cents a share.

The stock recently traded at $3.76, up 27.0%

“Our open system approach allows for the highest levels of flexibility and adaptability in the post COVID-19 environment,” Barry Weiner, Enzo’s president, said in a statement. "Our GENFLEX platform enables laboratories to use third-party or their own reagents on this open platform with ease and flexibility."

Weiner added that "Through this platform, we can provide substantially lower costs for molecular testing and address reimbursement pressure in one of the fastest growing segments of the clinical testing market. We remain committed to our growth strategy and expect that the higher margins achieved by the vertically integrated model of COVID-19 testing can be extended to a range of other molecular tests.”

The company also announced that founder Elazar Rabbani is stepping down as CEO, but will remain as a director and transition to a scientific role with the company once a successor is chosen.

In addition, Enzo has retained Cain Brothers, a healthcare investment banking firm, to identify strategic and commercial opportunities.

https://www.thestreet.com/investing/enzo-biochem-revenue-jumps-62-percent

U.S. backs distance of 3 feet between students; may help schools open

 The U.S. government on Friday updated its COVID-19 mitigation guidance to narrow the acceptable distance between students who are wearing masks to at least three feet from at least six feet, potentially easing the path for schools that have struggled to reopen under previous recommendations. The new recommendation from the U.S. Centers for Disease Control and Prevention is a boost to the Biden administration’s goal of reopening in-person learning for millions of public school students without sparking outbreaks of the virus.

“The revised CDC guidance is a great step,” said Dr. Amesh Adalja, a senior scholar with the Johns Hopkins Center for Health Security. It “reflects the fact that schools... are not drivers of infections,” he added.

Many schools continue to teach students remotely more than a year after 

the novel coronavirus prompted widespread closures across the United States.

The CDC said the new guidance was based on data from schools in Utah, Missouri and Florida that suggests transmission of COVID-19 in schools is relatively low when precautions such as mask-wearing are employed, including in cases where students do not maintain six feet of distance.

The guidance applies to students from kindergarten through high school and in areas with low, moderate, and substantial community transmission of COVID-19. Middle and high school students in communities with high levels of COVID-19 should stay six feet apart unless their schoolday contact can be limited to a single small group of students and staff.

“I want to emphasize that these recommendations are specific to students in classrooms with universal mask-wearing,” said CDC Director Rochelle Walensky in a Friday press conference.

Students should continue to maintain six feet of distance when interacting with teachers and other school staff and when eating, the CDC said.

The CDC has been under pressure to relax its guidance to schools and Walensky said this week that the agency was looking at data in part from a recent study in Massachusetts which suggested tighter spacing had not impacted COVID-19 transmission.

One of the CDC studies released on Friday looked at 20 elementary schools in Utah during a period of high COVID-19 transmission rates in the broader community. It showed that in-school transmission rates among masked students were low even though they maintained an average distance between seats of only three feet.

Many schools do not have the space in classrooms to maintain six feet between students, and outside of the United States public health agency recommendations for social distancing start at about three feet and range to more than six.

The guidance urged schools to conduct widespread COVID-19 testing of students and said such regular use of screening tests offers added protection for schools that require fewer than six feet of separation.

School districts should expand screenings for students participating in sports or other extracurricular activities, and consider universal screening prior to athletic events.

The agency continues to recommend quarantines for anyone who has been within six feet of someone sick with COVID-19 for more than 15 minutes within a 24-hour period.

The White House on Wednesday said it would allocate $10 billion to states to support COVID-19 screening testing for teachers, staff and students to assist schools resume in-person instruction.

The CDC said students are required to wear masks on school buses and any other forms of public transit they use to get to school. The agency issued an order in February requiring travelers to wear masks when using public transit.

The Biden administration has urged states to vaccinate teachers and childcare workers, with the goal of getting all of them inoculated by the end of March.

https://www.reuters.com/article/us-health-coronavirus-cdc-schools/u-s-backs-distance-of-3-feet-between-students-which-may-help-schools-open-idUSKBN2BB1OU

FDA's toughness toward AbbVie, FibroGen and Acadia ups worries of stricter drug reviews

 The FDA recently sent out two head-scratching notices to FibroGen and Acadia Pharmaceuticals, delaying decisions on their drug applications. Is it a sign of more challenging drug reviews to come? SVB Leerink analyst Geoffrey Porges warned investors that may be the case.

The FDA issued last-minute notices to FibroGen and its partner AstraZeneca on their anemia candidate roxadustat, and to Acadia for a label expansion on its neurology drug Nuplazid, raising surprising new hurdles they'll have to clear to win approvals.

Those two delays alone would not be enough to declare that the FDA is suddenly tightening its review process, Porges wrote in an investor note Tuesday, but then the FDA delayed its decision on label expansions for AbbVie’s immunology drug Rinvoq. That gives the theory of a more critical FDA significantly more weight, Porges said.

The delays, with the backdrop of a new President in the White House, “raise questions about whether the FDA under acting commissioner Janet Woodcock, who is effectively auditioning for the permanent role, is adopting a more stringent approach to drug reviews, at least for the time being,” Porges wrote. The Rinvoq decision indicates a "tougher posture from the FDA under the new administration,” he said in another note Wednesday,

The trouble started earlier this month with an announcement from FibroGen and AZ explaining that the FDA had told them it will convene an advisory committee to review roxa for treating anemia caused by chronic kidney disease.

An AdCom discussion, especially for a first-in-class drug-like roxa, isn't entirely surprising. But industry watchers and investors were shocked because the FDA told the companies three times that it wouldn’t hold such a meeting. What's more, the sudden change of stance came just three weeks before the scheduled decision date, which had already been pushed back by three months because of the FDA's request for more analysis of existing data.

As for Nuplazid, Acadia was aiming to expand the drug into dementia-related psychosis with a PDUFA data set for April 3. But on March 3, the FDA instead notified the company that it had identified deficiencies in the application that would preclude planned discussions about labeling and post-marketing requirements.

By Acadia’s account, it and the FDA has already agreed that one pivotal clinical program and supporting phase 2 data would suffice for the label expansion, and the company has responded to two data-related questions. Everything was still on track for the March 3 discussion, at least when Acadia reached out to the FDA on Feb. 18. And now, despite repeated attempts to obtain clarifications about the “deficiencies,” the FDA has been silent, the company said last week.

The Rinvoq setback extended the target action date for the drug’s application in psoriatic arthritis by three months to late second quarter. It came after the FDA requested an updated assessment of the benefit-risk profile for the JAK inhibitor in that indication. The FDA also raised questions related to a separate pending evaluation in atopic dermatitis. So the agency is now asking for more time to review the applications.

Porges suspects the FDA might have some concerns about how Rinvoq's higher, 30-mg dose, compares to the 15-mg dose of the drug that's approved in rheumatoid arthritis. Recently, the higher dose of another drug in the same JAK class, Pfizer's Xeljanz, was linked to an increased risk of serious heart-related problems and cancer.

“This is another example of what is clearly a new regulatory approach from the FDA—every potentially questionable or uncertain approval event seems to be pushed out, or re-evaluated, whereas investors may have had a high degree of confidence in their approval in the prior administration,” Porges said of the Rinvoq program in a Wednesday note.

A more restrictive FDA increases the risk to the biopharma industry, he said, warning investors that they should brace themselves for more such announcements. Now, drug programs with any “hair” on the phase 3 trial design or result could face review delays, AdComs, labeling restricting or outright rejections, he said.

https://www.fiercepharma.com/pharma/fda-s-moves-abbvie-s-rinvoq-fibrogen-astrazeneca-s-roxadustat-acadia-s-nuplazid-raise

Dialysis clinics should be able to vaccinate their patients on site

 

One year after Covid-19 was declared a national emergency in the United States, and with more than 525,000 Americans having lost their lives to it so far, the country is finally beginning to make progress toward getting a handle on this terrible pandemic, thanks to the distribution of several highly effective vaccines.

The vaccine distribution system seems to be working, despite considerable obstacles. We see it in the way that long-term care residents and staff, who were particularly hard hit over the past year, are experiencing falling infection and mortality rates that dovetail with extensive vaccination efforts. The success within the nation’s long-term care community after a challenging start is largely due to a partnership among stakeholders and the federal government that ensured appropriate allocation of vaccines — and end-to-end support — to protect vulnerable Americans in these facilities.

It’s now time to do the same for another of the nation’s most at-risk groups: Americans living with kidney failure who rely upon life-sustaining dialysis treatments. Policymakers need to work with the nation’s dialysis providers to get this done.

More than half a million Americans have kidney failure, also known as end-stage renal disease, and rely on dialysis to survive. They are disproportionately affected by Covid-19. A recent study found that 20% of people on dialysis who developed Covid-19 died from the infection, a significantly higher percentage than in the general population. Data from the Centers for Medicare and Medicaid Services show that people with kidney failure who get Covid-19 have the highest rate of hospitalization among all Medicare beneficiaries — a rate nearly seven times higher than the hospitalization rate for Medicare beneficiaries overall.

Communities of color are experiencing higher rates of Covid-19 infection, hospitalization, and death than white communities, with death rates twice as high among Black people as among white people. This mirrors the existing disproportionate impact people of color have long experienced with kidney failure. Black people make up just 13% of the U.S. population but account for 35% of Americans with kidney failure; they are nearly four times more likely than white people to develop it. Ninety percent of people needing dialysis also have comorbidities like heart disease, diabetes, and hypertension that also put them at risk of developing severe Covid-19 or dying from it.

Most people who need dialysis have been unable to socially distance since the pandemic began. They need to go to dialysis clinics three times per week for four hours at a time, where they are exposed to other patients and staff during their life-sustaining treatments. Many have limited mobility and challenges with transportation, limiting their ability to go to a vaccination center at a large stadium or a distant clinic difficult, if not impossible.

But there is a solution. If policymakers act now to allocate Covid-19 vaccines directly to the nation’s dialysis providers, they can administer them to patients. The qualified, experienced medical staff at dialysis centers and their established storage and safety protocols make it possible for the vaccine process to occur without delay to both patients and caregiving staff.

These clinics already vaccinate patients for influenza, pneumonia, and hepatitis B, and stand ready to vaccinate for Covid-19, with existing cold-storage capability, nursing personnel for vaccine administration, and supplies to manage any side effects. Dialysis facilities already function as patient-centered medical homes in which patients receive much of their overall medical care. This ensures that the clinics would be able to thoroughly follow up and provide patients with their second doses. Furthermore, experience shows that in-clinic vaccination significantly reduces refusal rates (to exceptionally low levels of 10% to 20%) which is key, since we need to ensure that as many people as possible receive the Covid-19 vaccine.

Federal vaccine allocation to community dialysis clinics cannot happen quickly enough. Lives depend on it.

There is a light at the end of this very long, very dark tunnel. Emerging on the other side of this health emergency means moving quickly and wisely to reach the groups most at risk for succumbing to Covid-19. On behalf of dialysis patients, we urge the federal government to act now to establish a federal vaccine allocation for dialysis clinics.

Donna Christensen is a member of the American Kidney Fund Board of Trustees, an emergency and family practice physician, former member of Congress from the U.S. Virgin Islands, and former chair of the Congressional Black Caucus Health Braintrust. LaVarne A. Burton is president and chief executive officer of the American Kidney Fund. Gary A. Puckrein is president and chief executive officer of the National Minority Quality Forum.

https://www.statnews.com/2021/03/19/dialysis-clinics-vaccinate-patients-on-site/