LogicBio Jumps on the Gene Therapy 2.0 Wave and Lines Up an IPO

Another gene therapy company is on its way to the public markets. But this one, LogicBio Therapeutics, is part of a newer crop of gene therapy developers that aim to overcome the potential shortcomings of the treatments on the market or in human trials. LogicBio’s technology is still preclinical, but the company aims to start human testing next year, and it is now planning an IPO to finance that research.

Cambridge, MA-based LogicBio set a preliminary $86 million target for its IPO. The company has applied for a listing on the Nasdaq exchange under the stock symbol “LOGC.” LogicBio aims to use the IPO cash to start its first clinical trial, for a rare inherited liver disease called methylmalonic acidemia (MMA).

Gene therapy has finally come of age after years of ups and downs. By introducing a functioning version of a faulty or missing gene into a cell. these treatments are intended to provide a long-lasting, if not permanent treatment for a genetic disorder. One product, for a genetic form of blindness, launched in the U.S. at the beginning of the year. More, for hemophilia, spinal muscular atrophy, and more, could follow, and several gene therapy developers are publicly traded. But even with the promise these treatments have shown, it’s unclear how long a therapy will last and who will respond. And when given to children, it’s possible some gene therapies might lose their effect over time as they grow and their cells divide.

LogicBio is one of several emerging companies trying to address these gene therapy issues. Its technology, called GeneRide, was developed to insert genes into specific locations in the genome. The company says this approach enables the transferred genetic material to remain stable as cells divide and tissue grows. The LogicBio gene therapy is inserted into the genome via a naturally occurring DNA repair process called homologous recombination. This process avoids using enzymes that cut DNA—a feature of gene-editing technologies such as CRISPR. These enzymes can cause unwanted and potentially dangerous modifications to the DNA, which in turn could cause tumors to form, LogicBio says in its prospectus. (LogicBio isn’t alone in trying to harness homologous recombination; Homology Medicines(NASDAQ: FIXX), which went public in March, is in the mix as well.)

LogicBio is starting with a potential treatment for MMA. Infants who have the condition can’t process certain fats and proteins, which leads to vomiting, dehydration, weak muscles, and developmental delays, among other problems. MMA has no FDA-approved therapies. Treatment for the disorder includes a low-protein and high calorie diet, antibiotics, and organ transplant, according to the Genetic and Rare Diseases Information Center. Depending on the severity of the disorder, MMA can be fatal.

The company’s MMA gene therapy, LB-001, is meant to help MMA patients produce more of the protein that they lack. LogicBio plans to start a Phase 1/2 clinical trial by the end of next year.

LogicBio is also developing potential treatments for hemophilia B; alpha-1 antitrypsin deficiency, which can lead to lung disease; and the rare disease Crigler Najjar Syndrome, which renders the body unable to clear a compound produced in the breakdown of old red blood cells.

LogicBio is led by CEO Fred Chereau, an industry veteran who has held senior roles at aTyr Pharma, Shire (NASDAQ: SHPG), and Genzyme. The company has raised $50 million in venture financing, most recently a $45 million Series B round of financing last year. LogicBio’s largest shareholder is OrbiMed, which holds a 35.3 percent stake in the company, according to the filing. Other large shareholders include Arix BioScience (LSE: ARIX), Pontifax, and BioDiscovery 5.

The company was founded in 2015, based on technologies licensed from Stanford University and the University of Texas System. The company spent $3.6 million on R&D in the first half of 2018, and had $18.2 million in cash at the end of June.

https://www.xconomy.com/boston/2018/09/26/logicbio-jumps-on-the-gene-therapy-2-0-wave-and-lines-up-an-ipo/

Big Pharma Seeks More Partnerships, Evidence in Digital Therapeutics

“Digital therapeutics” startups are starting to win more respect—and investment dollars—from pharmaceutical giants. But the two sides are still figuring out how to work together to capitalize on the potential for apps, devices, and other software-enabled technologies to impact patients’ health.

That’s what stood out to me the most as I listened to leaders from some of the world’s largest life sciences companies—Novartis (NYSE: NVS), Sanofi (NYSE: SNY), AstraZeneca (NYSE: AZN), and Johnson & Johnson (NYSE: JNJ)—talk about their firms’ interest in the nascent field of digital medicine at an industry conference, DTxDM East, held at a Boston waterfront hotel this week.

“These really, really large organizations want [digital therapeutics] to work and want to deploy investments into this,” said moderator Edward Cox, the CEO of San Diego-based digital therapeutics startup Dthera Sciences.

Pharma’s growing interest in digital medicine—in which electronics such as smartphone apps serve as the therapy—comes as the industry has gained momentum over the past year. Last September, a product developed by Pear Therapeutics, based in Boston and San Francisco, became the first software the FDA has cleared to be prescribed to help treat a disease (substance use disorder). The FDA is currently reviewing Akili Interactive Labs’ first experimental product—a mobile video game designed to assess and treat attention deficit hyperactivity disorder (ADHD)—after Boston-based Akili reported a successful 348-patient clinical trial last December.

Meanwhile, Click Therapeutics recently raised $17 million in a venture round led by Sanofi Ventures. New York-based Click will use the money to boost its efforts to win FDA clearance for a pipeline of mobile apps that would be prescribed to treat medical conditions—such as depression, insomnia, and chronic pain—either on their own or in combination with drugs or other standard treatments.

And in August, the FDA granted “breakthrough device” designation to a development-stage product from Cox’s company, Dthera. If the software product, DTHR-ALZ, ultimately wins approval, Dthera said it would become the “first non-pharmacological prescription treatment” for Alzheimer’s disease symptoms.

These milestones help bring legitimacy to an industry still proving itself. But there’s a lot of work to be done on that front, panelists said at Tuesday’s event.

“Over the next five years, we’ve got to focus on showing the evidence with digital therapeutics,” said Joris van Dam, executive director and head of digital therapeutics at the Novartis Institutes for BioMedical Research. “If we fail, it’s because we cannot show outcomes.”

Other big questions pharma companies are mulling: How should digital treatments be priced? How much will insurers pay for them? What’s the business value for drug makers? Can digital therapeutics businesses and their pharma partners make money from these products?

Digital therapeutics startups and pharma companies need each other, argued Melinda Decker, AstraZeneca’s head of “intelligent pharmaceuticals.” But the two sides’ attitudes and strategies don’t always mesh well.

“One of the challenges I find with digital therapeutics companies is their mindset is very much on, ‘How do we sell this as it is?’—rather than how [they] might partner with drug companies,” Decker said. “In dealing with the likes of Apple and Google, everyone is looking for, ‘How do I make Candy Crush and sell it for $5 a download?’ … [Therapeutics are] a completely different model.”

Bozidar Jovicevic, Sanofi’s vice president and global head of digital medicines, said he doesn’t like that pharma companies are sometimes “seen as distributors of digital therapeutics,” rather than more collaborative partners. Van Dam agrees that collaboration is key.

“These technologies have a tremendous opportunity to bring benefits to patients,” Novartis’s van Dam said. “We have a collective, not just opportunity, but collective obligation to get it right. What I don’t like is conversations that start with, ‘Yeah, pharma just doesn’t get it.’”

Pharma might not get it in some cases, he added, but all stakeholders are still trying to understand and advance the sector. The more important problem, van Dam argued, is “How can we work together?”

For his part, Dthera’s Cox said he doesn’t think pharma companies are “slow”—a common critique from startups in any sector seeking partnerships and investments from bigger, more established companies. Rather, “I think they’re rigorous,” Cox said. “It’s not the same thing.”

For patients, one of the key components will be making it easier to manage an expanding catalog of digital health products.

“All the solutions are very siloed,” said Jeff Mathers, senior director of software engineering and emerging technology at Johnson & Johnson Technology. “Nobody wants to download 35 apps” and share their medical information 35 separate times, he said. “That’s just not sustainable.”

In the coming years, Mathers envisions hospitals and clinics making it possible for patients to register for a variety of apps in one online location and more seamlessly use them. Otherwise, “they’ll just go crazy managing all these tools,” he said.

https://www.xconomy.com/boston/2018/09/26/big-pharma-seeks-more-partnerships-evidence-in-digital-therapeutics/

Midterms could boost some healthcare stocks, Barron’s says

Potential electoral results could favor the outlook for policies beneficial to a wide range of hospital, pharmaceutical, and other healthcare-related companies, Lauren Rublin writes in this week’s edition of Barron’s. Policy experts favor Centene (CNC), WellCare Health (WCG), Molina Healthcare (MOH), HCA Healthcare (HCA), Tenet (THC), Encompass Health (EHC), Becton Dickinson (BDX), Cerner (CERN), Dentsply Sirona (XRAY) and Teladoc Health (TDOC) as beneficiaries of Medicaid expansion under the Affordable Care Act, the reported noted, adding that is especially likely if Democrats win more state elections.

https://thefly.com/landingPageNews.php?id=2797366

270 Painkillers Per Person: DEA Probes Pill Mills in Small Tenn. Town

DEA agents discover another small town in America’s Rust Belt with an overabundance of opioids

The Drug Enforcement Administration (DEA) last week conducted inspections at several pharmacy locations in the Clay County, Tennessee town of Celina, following a massive spike of painkiller purchases from drug distribution companies.

According to the sales data, obtained by the DEA, several pharmacies purchased nearly 1.5 million pills in 2017, a number that is considered an anomaly of a rural area in America’s Rust Belt region.

Home to just 7,800 people, the pharmacies last year purchased enough opioids to provide 270 pain pills for every man, woman, and child living in the small Tennessee town.

In response to the opioid crisis, the DEA is now aggressively monitoring supply chains of pill distributors that primarily feed into hard-hit states.

“DEA’s action today is one of many proactive measures we are taking to help prevent drug diversion, abuse, and trafficking that end lives and destroy families and communities,” said Louisville Division Special Agent in Charge Chris Evans, who runs DEA operations in Tennessee, West Virginia, and Kentucky.

“When DEA sees abnormal patterns such as this one, we must act. Too many rural communities like Clay County are often targets for both addicts and drug traffickers who exploit the most vulnerable and who profit from addiction. We’ve lost too many Americans to opioid abuse,” Evans said.

Notice of inspection was issued to Anderson Hometown Pharmacy, LLC at 151 MacArthur Avenue, and Walgreens at 1000 Gainesville Highway. The DEA said an administrative inspection warrant was also issued to another pharmacy, Clay County Express Pharmacy, LLC at 651 Brown Street. Some of these inspections included a complete review of receipts and distributions, employee interviews, and all other pharmacy activities.

Last week, the Centers for Disease Control reported that drug overdose deaths in 2017 were up 7% from 2016 and that more than 72,000 American died the previous year — that is more than American soldier deaths in the Vietnam War (58,220 US military fatal casualties). This is a more than 200% increase over a decade. Of those overdose deaths, just over 49,000 were from synthetic opioids, which include prescription painkillers, heroin, fentanyl, and fentanyl analogs. Pain management, then pill abuse, is often the starting point for heroin and fentanyl addicts.

Days ago, we reported a similar incident in Williamson, West Virginia, where two pharmacies just four blocks apart pumped 20.8 million prescription painkillers in a town of only 3,191 residents.

It was reported that in December 2002 to January 2010, more than 335,000 prescriptions for painkillers were issued by Dr. Katherine Hoover at a small clinic in the struggling West Virginia town, a rate of about 130 per day.

Williamson is a small blue-collar city of some 3,000 residents just across the Tug Fork River from Kentucky. When the coal industry collapsed, it left behind many miners – many of whom were already reliant on painkillers.

However, like Williamson, Clay County is similar, both areas are located in America’s Rust Belt, where de-industrialization and high unemployment fuels the deadly cycle of addiction.

Now, these lost and forgotten towns in the Rust Belt are being pumped with record amounts of opioids by large pharmaceutical firms, who then in return, have local doctors and pharmacies dish out painkillers to residents.

Yet while the DEA is finally cracking down on opioid abuse, the one question left is: why did the government allow pharmaceutical companies and pill mills to pump millions of highly addictive opioids into the Rust Belt in the first place?

https://www.zerohedge.com/news/2018-09-29/270-painkillers-person-dea-investigates-pill-mills-small-tennessee-town

Tymlos Benefits Bone in Older Women

The benefits seen on bone mineral density (BMD) and fracture incidence reduction with abaloparatide (Tymlos) treatment for all postmenopausal women in the ACTIVE trial and its extension phase also were seen among the oldest members of the study cohort (ages ≥80), a post-hoc analysis found.

The Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial was an international randomized study that compared subcutaneous injections of abaloparatide, 80 µg daily, with subcutaneous teriparatide, 20 µg daily, and placebo for 18 months in almost 2,500 postmenopausal women. In the ACTIVExtend phase, all patients received alendronate 70 mg weekly through month 43.

“Efficacy and safety information on pharmacological treatments to prevent fractures is sparse in older patients, who are often excluded from clinical trials. Thus, it is important to understand the efficacy and safety of osteoporosis treatments in this population,” said Felicia Cosman, MD, of Columbia University in New York City, during a poster session at the American Society for Bone and Mineral Research annual meeting.

“Fractures are particularly common among older women, and the consequences take away from the quality and quantity of life in this group,” she told MedPage Today.

Abaloparatide is a selective activator of the parathyroid 1 receptor signaling pathway that is associated with increased bone formation. It was approved by the FDA in April 2017 for the treatment of postmenopausal osteoporosis.

A previous post-hoc analysis of ACTIVE participants in the placebo-controlled phase found that the efficacy and safety of abaloparatide among women, ages ≥80, were similar to what was seen in the overall study population.

The current analysis followed those 56 women whose mean age was 81.8 at baseline through an additional 24 months, during which all received alendronate, 70 mg weekly.

Among those who had initially been randomized to receive placebo, 18.5% had at least one prior nonvertebral fracture within the previous 5 years, as did 17.2% of those initially given abaloparatide. For prevalent vertebral fractures at baseline, the corresponding numbers were 18.5% and 41.4%, respectively.

During the 24-month follow-up phase when all patients were receiving only alendronate, the fracture rates among the age >80 subgroup were low. Among those who had initially received placebo or abaloparatide, respectively, the rates subsequent fractures were:

• New vertebral fracture: 4% vs 0%
• Nonvertebral fractures: 7.4% vs 4.2%
• Clinical fractures: 7.4% vs 4.2%
• Major osteoporotic fractures: 3.7% vs 0%

BMD at the total hip, femoral neck, and lumbar spine increased significantly more in the group that had initially received abaloparatide at all time points except for total hip at month 6 and femoral neck at month 12.

During the extension phase, 81.5% of the 27 age >80 patients who had initially received placebo reported any adverse event, as did 78.6% of those who had initially been given abaloparatide. For serious adverse events, the numbers were 11% and 14.3%, and for adverse events leading to discontinuation, the numbers were 7.4% and 3.6%. No adverse events resulted in death.

The specific adverse events in the placebo versus abaloparatide groups included arthralgias (11.1% vs 7.1%), back pain (7.4% vs 10.7%), dizziness (11.1% vs 3.6%), dyspepsia (3.7% vs 10.7%), and hypertension (11.1% vs 3.6%).

“Now we have data to suggest that when treating older patients with a drug like Tymlos, we should expect to get very good results,” Cosman concluded.

The study was funded by Radius Health. Some co-authors are company employees.

Cosman dislcosed no relevant relationships with industry. Some co-authors disclosed relevant relationships with the NIH, Radius Health, Amgen, Eli Lilly, Merck, and Tarsa.

• Primary Source

  American Society for Bone and Mineral Research

  Source Reference: Greenspan S, et al “Abaloparatide effect on bone mineral density and fracture incidence in postmenopausal women with osteopososis aged 80 years or older: results from the ACTIVExtend phase 3 trial” ASBMR 2018; Abstract 0907.

https://www.medpagetoday.com/meetingcoverage/asbmr/75413

HHS funds further research of a wearable device that could warn of early illness

It’s a device the size of a key fob that measures breathing, heart rate, sleep, and movement. It can be attached to clothing such as undergarments, requires no recharging, and will survive cycles through the washer and dryer.

The U.S. Department of Health and Human Services (HHS) is hoping that one day this easy-to-use monitor will issue early warnings that the individual wearing it is about to become sick. The implications for health systems managing population and chronic health initiatives is obvious: early detection and treatment of illnesses such as the flu could prevent hospitalizations, improve outcomes, and lower costs.

San Francisco-based Spire received a $62,200 grant from HHS to further gather data from these devices and discover, through artificial intelligence, if patterns exist that can predict the onset of illness. The total cost of the project is $88,860, with Spire providing the retaining funds.

The product, Health Tag, is already commercially available for consumer health and wellness use to monitor sleep, stress, and activity. Currently available in a variety of package sizes, with a heavy adhesive for each unit that does not loosen during laundering, individuals using the sytem can attach the monitors to frequently worn clothing and never have to check them again to download information or change batteries. Collectively, an 8-pack lasts about 18 months, says Jonathan Palley, CEO and co-founder of Spire.

The device can send messages to the user’s cell phone to report findings and alert the wearer to real-time bio-signals, like heart-rate and breathing variability, stress levels, and other changes in the user’s unique health signature.

One reason Palley believes Health Tag offers advantages over other such devices on the market is that it requires minimal interaction to operate.

“It really solves the adherence problem,” Palley says. Ideally, data from such monitors needs to be collected continuously, but If constant interaction is required, compliance drops, he explains.

The grant to Spire was awarded through the Division of Research, Innovation and Ventures (DRIVe), a division of the Biomedical Advanced Research and Development Authority(BARDA) in the HHS Office of the Assistant Secretary for Preparedness and Response. One expected outcome from this venture, says Palley, is that BARDA will be able to accelerate development toward Food and Drug Administration 510K clearance.

Palley says he was not aware of opportunities to work with BARDA before the agency approached his company. DRIVe is spurring innovation in the way the government prevents, detects, and responds to major health security threats. The grant was awarded as part of DRIVe’s Early Notification to Act Control and Treat (ENACT) portfolio to develop products that will let people know they are sick before the first symptom appears.

A news release from DRIVe further explains the organization’s interest, “Innovative technologies like wearable ENACT products hold the potential to also strengthen the nation’s ability to protect Americans from health security threats and to save lives.”

In July, BARDA granted funding to two California-based biotech companies for development of at-home flu tests. In September it announced an award to EnLiSense to accelerate development of a wearable device that detects infections in a person’s sweat. The division also has an initiative related to prevention and early detection of sepsis.

https://www.healthleadersmedia.com/innovation/could-device-bring-us-one-step-closer-predicting-illness

Early Parkinson’s patients waiting too long to seek medical evaluation

Figure 1. Relationship between time of diagnosis, need for symptomatic therapy and the opportunity for a patient to participate in an early PD disease modifying therapy trial. Credit: University of South Florida

The time between diagnosis and the institution of symptomatic treatment is critical in the effort to find a cure for Parkinson’s Disease (PD). A paper published in Nature Partner Journal: Parkinson’s Disease notes too many early PD patients wait too long before seeking medical attention, or start taking symptomatic medications before they are required, thereby dramatically shrinking the pool of candidates for clinical trials.

Parkinson’s disease is a disorder of the central nervous system that affects movement. Symptoms include tremors, stiffness, and slow and small movement. The pace of progression varies among patients, making the months following diagnosis crucial to researchers studying the disease’s progression.

“The critical time of about one year from when the patient can be diagnosed with early PD based on mild classic motor features until they truly require symptomatic therapy can be considered the Golden Year,” said lead author Robert A. Hauser, MD, director of the Parkinson’s & Movement Disorder Center at the University of South Florida. “It is during this early, untreated phase, that progression of clinical symptoms reflects the progression of the underlying disease.”

Hauser says that in order to determine whether or not a potential disease slowing therapy is actually working, they must be able to compare the therapy to a placebo without interference from symptomatic treatment. Otherwise, they won’t know if the therapy is slowing the disease’s progression or if they are just seeing the effects of symptomatic treatment.

This requires patients to seek assessment soon after they notice the onset of tremor or slow movement. In addition, physicians should consider referring patients to clinical trials soon after diagnosis and delay prescribing symptomatic medication until it’s necessary. If a patient waits until symptomatic treatment is necessary, the opportunity to participate in these crucial clinical trials is lost.

 Explore further: DBS treatment may slow the progression of Parkinson’s tremor in early-stage patients

More information: Robert A. Hauser. Help cure Parkinson’s disease: please don’t waste the Golden Year, npj Parkinson’s Disease (2018). DOI: 10.1038/s41531-018-0065-1

https://medicalxpress.com/news/2018-09-early-parkinson-patients-medical.html