2018’s Must-Have Medical Apps for Primary Care Docs

Earlier this year, we put together a list of what we thought were the best medical apps for healthcare providers. Now at the end of 2018, we’re augmenting that list to give you a full picture of what we think are the must-have medical apps for those in primary care.

Safe Motherhood Initiative: ACOG DII SMI

Quick reference for common obstetric emergencies

Many of us in family medicine practice full-scope — including obstetrics and urgent/emergent care. Routine vaginal deliveries can quickly deteriorate into one of many frightening obstetrical emergencies. Recent information from the CDCshows a sobering statistic that maternal mortality in the U.S. is increasing rather than decreasing. The number of reported pregnancy-related deaths in the U.S. steadily increased from 7.2 deaths per 100,000 live births in 1987 to 18.0 deaths per 100,000 live births in 2014. The three most common causes of maternal mortality worldwide and in the U.S. have not changed: postpartum hemorrhage, venous thromboembolism, and severe hypertension of pregnancy. The Safe Motherhood Initiative (SMI) is an initiative of the American College of Obstetricians and Gynecologists (ACOG) District II in New York State. This group links hospitals across the state together and provides healthcare bundles and education aimed at reducing mortality from these three most common lethal pregnancy complications.

ACOG DII SMI is a combination of expert opinion, ACOG position statements, and algorithms supported by evidence-based medicine, clinical practice guidelines, and standard of care medical practice. The app contains easy to follow checklists, algorithms, and teaching slides targeted to the three most common causes of maternal mortality.

Psych on Demand

Screening and assessment of mental health conditions

Mental health conditions are exceedingly common and costly in the U.S. medical system. Recent statistics from the CDCestimated that they account for 60 million visits to primary care and 6 million ER visits annually. Depression alone accounts for more than 10% of all primary care visits. These conditions result in a sobering 44,000 suicide deaths per year in the U.S.

Screening for these conditions is commonly performed in most primary care practices with supporting recommendations from the U.S. Preventive Services Task Force (USPSTF) for conditions such as depression, alcohol abuse, etc.

Psych on Demand is an app by a board-certified psychiatrist that puts all of the most common (and some uncommon) screening instruments in one user-friendly app. The app contains more than 35 instruments covering disorders including depression, post-traumatic stress disorder (PTSD), attention deficit-hyperactivity disorder (ADHD), anxiety, bipolar disorder, and many others.

It’s an exceptional value for all who screen and treat mental health disorders.

American Diabetes Association (ADA) Standards of Care 2018 App

The wait is over!

Type 2 diabetes remains a global epidemic. According to a 2017 CDC report, over 100 million Americans have prediabetes or diabetes. Diabetes was the number seven leading cause of death in 2015. The World Health Organization (WHO) published a report showing a quadrupling of the prevalence of diabetes since 1980 worldwide. According to the CDC, 1 in 4 with diabetes do not know they have the disease. Diabetes creates a significant burden on morbidity and mortality and per the ADA, came at a cost of $327 billion in 2017 in the U.S. alone. The ADA app had not been updated since the release of the 2014 standards. In June, the app was updated to the 2018 ADA Standards of Care and completely redesigned — finally. The latest version of the app includes detailed information on diagnosing and treating diabetes, lifestyle and nutrition recommendations, and specific guidelines from lipid management to retinopathy treatment.

ADA Standards of Care is well-referenced and provides content any medical student or seasoned attending could benefit from having available at the tips of their fingers. The app contains hyperlinks to references, comprehensive PDFs, and links to online ADA articles.

DizzyFix

Teaches the Epley maneuver for vertigo on your smart device

“I’m dizzy, doctor!” Those were the words of a patient I saw in clinic recently. Upon further questioning, it was clear this patient had vertigo. The question was what type? Luckily, a good patient history and physical exam can both make a solid diagnosis and in some cases, treat the patient. Primary care providers must know how to properly perform the Dix-Hallpike maneuver to help make a diagnosis of vertigo, especially the most common form, benign paroxysmal positional vertigo (BPPV). Luckily, the vast majority of vertigo cases seen in primary care are due to BPPV, and this very disturbing condition (for the patient) can be effectively treated in nearly 90% of the cases by proper performance of the Epley maneuver.

An enterprising ENT physician and inventor in Canada created a unique solution to BPPV. He created an app called DizzyFix for providers to teach proper diagnosis and treatment of BPPV using the Dix-Hallpike and Epley maneuvers, and the DizzyFix device that patients can place on any “ball cap” to guide them through the Epley Maneuver at home.

CDC PneumoRecs

Ensures your patients receive the correct pneumococcal vaccines at the right time in the right sequence

One of the most common tasks during clinic is to ensure my patients are up to date on their vaccinations. In 2015, the CDC/FDA/Advisory Committee on Immunization Practices (ACIP) introduced the new pneumococcal conjugate 13 valent vaccine (PCV13) for use in adults in addition to the pneumococcal polysaccharide 23 valent vaccine (PPSV23). For many of our clinic’s nursing staff, residents, and faculty, the transition caused some confusion. The guidelines have been revised slightly since then with the most current pneumococcal vaccine guidelines published in November 2018. Despite updates to existing “shots” apps such as Shots by STFM, CDV Vaccines, and ACP Immunization Advisor, the process can still be challenging to explain to patients and ensure immunizations are given at the right time and in the proper sequence.

Recently, the CDC entered the pneumococcal vaccines fray with their own app to help providers — CDC PneumoRecs. This app covers both infant/child as well as adult pneumococcal vaccines. The app uses a patient’s date of birth (DOB) to calculate which vaccines the patient requires, when, and in what sequence based on age and risk factors.

https://www.medpagetoday.com/blogs/iltifathusain/77177

Low-Risk Transcatheter Aortic Valve Replacement Highly Anticipated for 2019

Transcatheter aortic valve replacement (TAVR) expansion into a low-risk population is on the table in 2019, as two pivotal trials and regulatory review for this indication are widely anticipated.

PARTNER 3 and CoreValve Low Risk will have short-term results available in low-risk patients who got the Sapien 3 valve from Edwards Lifesciences and the Evolut R from Medtronic, respectively, for severe aortic stenosis. Patients have been selected such that no one will have surgical mortality risk exceed 2% in PARTNER 3 and 3% in CoreValve.

Both studies are on track to be presented in March at the American College of Cardiology’s annual meeting. If the results are positive for both, the FDA is highly likely to grant commercial approval for a low-risk indication in the latter half of 2019, speculated George Deeb, MD, who is a part of the CoreValve Low Risk trial’s steering and screening committees.

“If the low-risk trials show that TAVR is non-inferior to SAVR [surgical aortic valve replacement], then the future will have TAVR dominating this arena,” said Deeb, a thoracic surgeon at the University of Michigan, Ann Arbor.

At his institution, clinicians take a multidisciplinary heart team approach in presenting all the appropriate options to the patient and taking into consideration the patient’s preference to come to a shared decision for treatment, he said.

Still, “the majority of patients who have three-leaflet aortic stenosis that are moderate-to-greater risk, they’re going to choose TAVR. The majority of our valves are TAVR. Once low-risk is approved, the majority of patients will request TAVR,” Deeb predicted.

Exceptions, he noted, will be the younger patients who want a surgical mechanical valve that will last longer between interventions.

The question of durability has been an Achilles heel of TAVR. While European data seem to suggest similar longevity between transcatheter and surgical tissue valves out to 5 to 7 years, it’s not clear if that is good enough to get TAVR into younger patients.

“Durability getting into younger patients will still be a big question mark. It’s not right to assume it will be as good as the bioprosthetic surgical valves,” said Richard Shemin, MD, chief of cardiac surgery at David Geffen School of Medicine at UCLA and a site investigator for PARTNER 3.

Certain mechanical properties of TAVR valves may make them more prone to tissue deterioration, he suggested in an interview. For one, the tissue is crimped thinner than the tissue in surgical valves, and it is also placed on a wire stent instead of mounted on a frame.

“The trials will answer many questions and pose many questions. These patients are low-risk for surgery, but in general, usually these low-risk trials do not necessarily have young patients,” Shemin said.

He stressed good clinical judgment even if the indication for TAVR in low-risk patients is approved by the FDA as many expect in 2019.

Expansion of the Sapien line has run into a bit of a snag, in the meantime. The next-generation Sapien 3 Ultra was cleared by European regulators for treating severe, symptomatic aortic stenosis this year but had a wrench thrown into its debut in Europe because of a patent dispute between Edwards Lifesciences and Boston Scientific. The Ultra did get FDA approval, which had been expected by the end of 2018.

Beyond device evolution and expansion into low-risk patients, companies are also trying to make TAVR a treatment for patients before symptoms start. The EARLY TAVR trial, for example, is investigating how this approach compares to clinical surveillance in asymptomatic individuals with severe aortic stenosis.

“Whatever’s good for patients is good for the cardiac surgeon and the interventionalist,” according to Shemin. “There’s often extreme enthusiasm if a trial was good to maybe extend [the treatment] to a patient population that was never tested. I think like everything else, people have focused on the big picture, but the devil’s in the details,” he emphasized.

https://www.medpagetoday.com/cardiology/pci/77156

Artificial fingerprints could hack into a third of smartphones

• Researchers at New York University and the Michigan State University have developed images of fingerprints that have the potential to unlock devices.
• They told CNBC their findings suggested such an attack could be profitable for hackers.
• The way devices store images of fingerprints could be made more secure, the researchers said.

Artificial fingerprints have been developed by researchers who say they could one day be used to hack into everyday devices.

Researchers from New York University and Michigan State University successfully generated what they call “DeepMasterPrints” earlier this year. These are machine-learning methods that act as a kind of “masterkey” which, the researchers claim, have the potential to unlock around one in three fingerprint-protected smartphones.

In the paper released in October, the authors said synthetic fingerprints could be “used by an adversary to launch an attack … that can compromise the security of a fingerprint-based recognition system.”

Philip Bontrager, Aditi Roy, Julian Togelius, Nasir Memon and Arun Ross, the researchers behind the study, said the way fingerprints were recognized on smartphones and other devices was often problematic.

“Phones and many more devices don’t capture your entire fingerprint,” they told CNBC over the phone. “There’s not enough space on the device, so they capture a partial fingerprint — which is not as secure as the full image. (People assume) the device stitches images of their fingerprint together, but that’s not really what happens — it keeps sets of partial fingerprints.”

For each finger stored in place of a password, the device keeps multiple images. If someone then uses their finger to unlock that device, they only need to match one of the partial fingerprint images on its security system.

“If you store images for three of your fingers the device may keep around 30 partial fingerprints,” the researchers said. “With MasterPrints you just have to create a few — five or ten and I’m in business.”

They added that this could unlock a “reasonably large” number of phones — just under a third.

“If every fifth phone works it would be a profitable scam,” they said.

Defenses increasing

While the researchers told CNBC that their findings could be a potential threat to security systems, there were things software developers could do to make such an attack harder to pull off.

“Research in assessing vulnerabilities in a fingerprint recognition system is a constant arms race between fixing vulnerabilities and discovering new ones,” the paper said. “It is important for researchers to probe for new vulnerabilities so that loopholes can be fixed.”

Many developers were already making fingerprint scanners more secure by moving sensors from devices’ buttons to screens, allowing them to pick up higher resolution images.

“Some smartphones have the sensors on the side buttons, which are very thin — they’re convenient but less secure,” the researchers told CNBC. “Their sensors only register a quarter or so of the fingerprint’s features.”

What’s at stake?

Most smartphones give users the option to set up fingerprint recognition as a way to access their device, as well as a way to verify payments and unlock bank accounts. Amazon’s U.K. site offers more than 2,000 products relating to fingerprint security, including padlocks and safes.

In July, it emerged that Mastercard was in talks with British banks about introducing cards with integrated fingerprint scanners, opening the market up to biometric payment systems.

Big firms are also using biometrics to provide smoother experiences for customers. Delta already allows its passengers to use their fingerprints to board flights and access airport lounges, and car rental firm Hertz recently unveiled a biometric system at Atlanta International Airport to make renting a car up to 75 percent faster.

Clear, the firm behind Delta and Hertz‘s fingerprint recognition technology, told CNBC via email that as long as companies provided the appropriate security, there was “no question” that biometrics were more secure than a traditional ID.

Clear “does not rent, sell or share member data. The platform is also Safety Act Certified by the Department of Homeland Security as a Qualified Anti-Terrorism Technology,” a spokesperson told CNBC via email this week.

“We go to great lengths to secure member data, protect privacy, and enable exceptional experiences. We operate a closed network that is not exposed to the internet, and our members’ biometrics are encrypted at all times, in transit and at rest.”

Spokespersons for smartphone makers Apple and Google were not immediately available for comment when contacted by CNBC. Mastercard and Samsung declined to comment on the research.

https://www.cnbc.com/2018/12/28/research-claims-fake-fingerprints-could-hack-a-third-of-smartphones.html

Is the future of dog health in a DNA test?

Information from commercial DNA tests helped reveal the genetic origins of the husky’s captivating blue eyes and may even help us treat some diseases. But not everyone agrees.

Have you ever been captivated by the bright blue eyes of a husky puppy? Well, now scientists have discovered the genetic inner workings behind the blue eyes of Siberian huskies.

The new study found that a duplication in a stretch of DNA on the dog chromosome 18 was associated with the husky’s icy stare. This stretch of DNA is close to a gene called ALX4, involved with eye development in humans. This is a good indication the region is involved in the same function for dogs.

The study was led by American company Embark, which makes DNA tests for dogs. These tests aim to uncover potentially preventable diseases in our furry friends. They’re also used to confirm the breed or breed mix of your dog or just about any other trait of the animal.

The dog DNA collected can also contribute to valuable scientific research, as this study shows. But some veterinarians say it’s too early to hang all our hopes on DNA testing.

Old dog, new tricks

Discovering the secrets behind huskies’ beautiful blues was made possible by analysing the genome of 3248 dogs and using an innovative approach to collect information. The company reached out to their customers for information about their dogs, even asking for photos of their dog’s eye colour. With this information at hand, the team was able to focus on analysing the genome of blue-eyed dogs.

The approach was not only new but also pretty clever, as it allowed researchers to analyse a large dataset without having to spend any time or money collecting samples.

“It’s a new way of doing dog genetic research. Instead of an academic researcher like me needing to ask the federal government for money in order to sponsor a study on one particular thing, dog owners pay for the genetic testing up front, and then the genetic data can be quickly put to use by researchers investigating a whole host of different studies,” says Adam Boyko, a co-author of the study and co-founder of Embark. Now that the research is published, the data will be available for anyone wishing to use it for other studies.

This study represents the first example of how consumer-based genetic tests can be used on animals to do basic research and get some answers.

Credit: Embark

Sick as a dog?

Embark is one of several companies offering genetic tests for dogs. Other companies are also offering similar tests for cats. Overall, a lot of people are excited about testing their beloved pet’s DNA. But many scientists have expressed doubts and concerns about what we can actually learn about our dog’s health with these tests.

While these test may reveal that your dog has a genetic mutation that is linked to a disease, this does not necessarily mean that your dog will go on to develop the disease. Some experts actually argue that these genomic pet tests are selling false hope.

“We simply don’t have any of the necessary follow-up data … to predict whether an individual dog with a genetic variant associated with a disease will actually go on to get sick,” says Lisa Moses, a veterinarian at the Angell Animal Medical Center in Boston.

But cases of people using these tests to make medical decisions for their pets are already cropping up. One example was a 13-year-old dog that was “put to sleep” following a genetic test. The dog started having trouble walking and controlling its bladder and bowel movement. Her owners bought a genetic test and found that the dog carried a mutation linked to a neurological disorder. Based on this test (and, likely, the problems troubling the poor dog), the owners decided to euthanise the dog. But only a small percentage of dogs that test positive for that common mutation end up developing a disease, said the authors of the Nature comment article, and there are other treatable conditions that could also explain the symptoms the dog was suffering.

“Most worrisome is that people are using some of the DNA tests as a confirmation that a dog has a certain disease if they have signs that could be caused by that disease. The tests are not appropriate to confirm disease without other pieces of evidence, since a genetic variant is not the same as a disease state,” says Lisa.

But there are some good examples too of the benefits of dog genetic testing. “I remember one case where an adult mixed-breed dog was genetically at risk for a disorder known as exercise-induced collapse, and it explained the spells he would have when he would exercise in the summer,” Adam says.

In another example, dog owners who were having trouble training their dogs had them tested. They discovered that the dogs were not of the breeds they originally thought. “By understanding the breed make-up, they could better give their dog the environment and training their dog needed,” Adam says.

To test or not to test

The main take-home message is that a genetic test is not the final word—having a mutation linked to a disease is not the same as having the disease.

“A genetic test is not a substitute for a veterinarian, a test alone won’t diagnose the presence of a disease! I do think most owners realise this, but clearly more education is needed if some people are using genetic testing inappropriately,” says Adam.

https://phys.org/news/2018-11-future-dog-health-dna.html#jCp

15 For ’19: Key Clinical Data to Watch For Next Year (Part 2)

On Monday, Xconomy began our annual look ahead at clinical trials that could define biotech and have profound healthcare effects in the coming year. Today we’re circling back with the rest of the list, which includes studies of drugs for nonalcoholic steatohepatitis, cystic fibrosis, spinal muscular atrophy and more. Read on for the details. [Editor’s note: Alex Lash, Corie Lok, and Frank Vinluan contributed to these reports.]

Disease area: Nonalcoholic steatohepatitis (NASH)

Companies: Intercept Pharmaceuticals, Genfit

Trial: REGENERATE, RESOLVE-IT

Data expected: 1H 2019 (REGENERATE), 2H 2019 (RESOLVE-IT)

Why We’re Watching: Sometimes diseases are preventable, but prevention isn’t likely to make a huge dent. There’s no starker example than bad diet and exercise habits leading to a fatty liver. Sometimes the condition advances into nonalcoholic steatohepatitis (NASH), and the liver becomes inflamed, stiff, and scarred. NASH can cause cancer and leads to thousands of liver transplants a year in the U.S. alone. The disease has now spread across the globe.

There is no current treatment for NASH. The race to provide one is at fever pitch, with Intercept Pharmaceuticals (NASDAQ: ICPT) of New York and French firm Genfit (NASDAQ: GNFT) in the lead. Intercept should be the first to present key Phase 3 data, and its once-a-day pill obeticholic acid (Ocaliva) already has FDA approval in a related liver disease.

In its 2,370-patient REGNERATE trial, Intercept has set out to show that obeticholic acid over 18 months can reduce liver scarring or achieve “resolution”—an agreed-upon abatement of various symptoms. It only needs obeticholic acid to hit on one or the other to prove successful, the company said when it amended the REGENERATE design in early 2017.

More broadly, Intercept hopes to improve patients’ long-term outlooks by comparing rates of death, hospitalization, cancer, and more among patients who are or aren’t on its drug. Intercept is testing two doses of its drug against placebo. Liver specialist Anjana Pillai of the University of Chicago told Xconomy in 2017 that doctors ideally want to see a NASH drug reduce all three of the disease’s hallmarks: scarring (also known as fibrosis), inflammation, and liver fat.

Genfit says its first cut at Phase 3 data will come late in the year, from the 2,000-person RESOLVE-IT study of its own once-a-day pill, elafibrinor. Unlike Intercept, Genfit is only shooting for NASH resolution. Reduction of fibrosis is a secondary study goal. (Like Intercept, Genfit will measure long-term outcomes; results will come much later and won’t likely be part of the company’s request for regulatory approval.)

Behind the two leaders are a bevy of companies, large and small, with NASH candidates. The list includes Gilead Sciences (NASDAQ: GILD), Allergan (NYSE: AGN) and its partner Novartis (NYSE: NVS), NGM Biopharmaceuticals and partner Merck (NYSE: MRK), Madrigal Pharmaceuticals (NASDAQ: MDGL), and Viking Therapeutics (NASDAQ: VKTX).

Roche, Pfizer (NYSE: PFE), Bristol-Myers Squibb (NYSE: BMY), 89Bio, and Akero Therapeutics are also in the mix. The need is large enough that the first drug to market will likely have stiff competition in the years to follow.

Disease Area: Rare genetic diseases

Companies: CRISPR Therapeutics, Editas Medicine, Sangamo Biosciences

Trials: NCT03745287, NCT03041324

Data Expected: 2019

Why We’re Watching: This year marked the first injection of a genome-editing medicine into a patient as part of a clinical trial. The early peek at the historic data—only four patients’ worth—didn’t go so well for the medicine’s developer, Sangamo Biosciences (NASDAQ: SGMO). Sangamo says more data from the early study, which aims to treat the rare, deadly Hunter syndrome, will come next year.

Sangamo uses its wholly-owned genome-editing technology, called zinc finger nucleases, which could explain why the company has flown under the radar. In other words, it’s not using CRISPR, the editing system that has spread to labs (even high-school labs) around the world.

In 2019, we could have our first CRISPR-in-humans results. (We’re not counting the unconfirmed claim of Chinese researcher He Jiankui that he edited human embryos and helped bring to life the world’s first gene-edited babies.) Two U.S. biotechs are launching medical trials with CRISPR: CRISPR Therapeutics (NASDAQ: CRSP) and Editas Medicine (NASDAQ: EDIT).

First up are CRISPR and its partner Vertex Pharmaceuticals (NASDAQ: VRTX) with a treatment for sickle cell disease called CTX001. The two were freed to start their trial in October when the FDA lifted a temporary hold on the study that paused enrollment. The phase 1/2 trial could include up to 45 patients with severe sickle-cell cases, which is marked by a lack of oxygen-carrying hemoglobin in the blood.

With CTX001, investigators will take patients’ blood stem cells, edit them to boost production of a fetal form of hemoglobin, and put those cells back into patients. It’ll actually be the second CRISPR Therapeutics study to start: an early-stage trial of CTX001 is already underway in Europe for patients with another hemoglobinopathy, beta-thalassemia.

Following closely behind is Editas Medicine (NASDAQ: EDIT), which the FDA cleared last month to start human studies of its experimental treatment EDIT-101. Editas and partner Allergan (NYSE: AGN) will test EDIT-101 in patients with Leber congenital amaurosis type 10, a rare genetic disease that causes vision loss. The CRISPR-based treatment will be injected directly into the retinas of 10 to 20 patients, where it is supposed to delete a disease-causing mutation in light-sensing retinal cells.

Unlike Sangamo and its zinc fingers that aim to edit the DNA in the liver cells of Hunter patients, CRISPR Therapeutics and Editas aren’t injecting CRISPR into the bloodstream. CRISPR Therapeutics is editing cells outside of the body, while Editas will inject CRISPR into the eye, a self-contained organ with reduced immune responses. Those strategies may help minimize some of the potential risks of CRISPR-based drugs that scientists have illuminated over the last year, like unintended edits and pre-existing immunity to key CRISPR components. But only clinical data will reveal how those risks play out in humans, which is why we are watching each study.

CRISPR Therapeutics could provide data in 2019, according to clinicaltrials.gov records. Both CRISPR Therapeutics and Editas declined to comment on timelines.

Disease Area: Cardiovascular

Companies: The Medicines Co./Alnylam Pharmaceuticals

Trials: ORION-9, ORION-10, ORION-11

Data Expected: 2H 2019

Why We’re Watching: It’s been a slog for a new class of injectable, cholesterol lowering medicines known as PCSK9 inhibitors. Approved in 2015, these drugs were hailed as a huge medical advance that could lower  “bad” cholesterol, or LDL-C—particularly in people who have bad reactions to standard-of-care statins or who can’t lower their cholesterol enough with them.

But payers balked at the high prices, about $14,000 a year, and waited for evidence that the drugs could prevent heart attacks or strokes too. The developers of the two PCSK9 blockers, Regeneron Pharmaceuticals (NASDAQ: REGN) and Amgen (NASDAQ: AMGN), came through with huge studies and at least some evidence of those measures, but insurers still balked at reimbursing their drugs, alirocumab (Praluent) and evolocumab (Repatha).

The companies have since cut prices and worked creative deals with payers to try to move the needle. But now even lower-cost alternatives are in the works. A pill from Esperion Therapeutics (NASDAQ: ESPR) called bempedoic acid is headed for an FDA review in 2019. And we’ve got our eye on another experimental drug: inclisiran, from The Medicines Co. (NASDAQ: MDCO) and partner Alnylam Pharmaceuticals (NASDAQ: ALNY).

The proposed benefit is convenience. Alirocumab and evolocumab have to be administered once or twice a month, while inclisiran could potentially be injected just two or three times a year, which may help with patient compliance and lead to better control their cholesterol. MedCo has made a huge bet on that thesis: it jettisoned other programs, chopped its workforce, and raised $150 million in convertible notes to pay for the pricey late-stage studies underway.

In ORION-9, ORION-10 and ORION-11, patients with heart disease are getting either a placebo or four total doses of inclisiran over the course of 18 months. Data are expected in the second half of 2019.

Will the results matter to payers and physicians, or will they wait for the results of MedCo’s big “outcomes” study, akin to the ones Amgen and Regeneron have already run? And if inclisiran makes it to market, how will MedCo—which has seen the commercial struggles of Regeneron and Amgen—price the drug? Those are some of the questions ahead for MedCo, which expects to file for FDA approval by the end of 2019 if the ORION results are positive.

Like alirocumab and evolocumab, inclisiran aims to lower the levels of the protein PCSK9; lower levels correlate with better clearance of LDL from the blood. Inclisiran uses RNA interference—a method of stopping genes from producing disease-causing proteins—to prevent the liver from making PCSK9 in the first place. RNAi is a drug-making method that has just come of age after years of ups and downs. In August, Alnylam’s patisiran (Onpattro), for a rare genetic disease, became the first-ever FDA-approved RNAi medicine.

The ORION studies are the first big test of RNAi in a broader population and could signal that this new way of attacking disease could have a wider field of play.

Disease Area: Spinal muscular atrophy

Companies: Novartis, Roche

Trials: STRONG/SPR1NT (Novartis), FIREFISH/SUNFISH (Roche)

Data Expected: 1H 2019 (Novartis), 2019 (Roche)

Why We’re Watching: Things have begun to change for patients with the rare genetic disease spinal muscular atrophy. And that change is about to accelerate.

SMA robs people of their ability to walk and function independently. Some types of SMA can be lethal. There were no drugs available until late 2016, when the FDA approved nusinersen (Spinraza) from Biogen (NASDAQ: BIIB), an RNA-based treatment infused a few times a year. In clinical studies nusinersen showed the ability to slow the disease’s progression for people with multiple forms of the disease. A gene therapy and a pill may soon follow, setting the stage for multiple treatment options and a high-stakes commercial battle between Biogen, Novartis, and Roche.

Likely on its way first is a gene therapy, AVXS-101 (Zolgensma). Novartis paid $8.7 billion to buy AveXis and get its hands on the treatment, which offers long-lasting effects from a single infusion and is under regulatory review in the U.S., Europe, and Japan. But the data are only for SMA Type 1, the most severe form that afflicts infants.

Next year, Novartis aims to prove the gene therapy is effective in other groups, as Biogen has shown with nusinersen. Watch for two key studies: STRONG, for Type 2 patients; and SPR1NT, for patients with Type 1, 2, or 3 who have yet to show symptoms. Both are expected to produce data no later than the American Academy of Neurology’s big meeting in May 2019.

Then there’s Roche. Through an alliance with PTC Therapeutics (NASDAQ: PTCT), the company is developing a drug called risdiplam. Like nusinersen and AVXS-101, risdiplam works by boosting levels of the key protein, survival motor neuron, that SMA patients lack. But risdiplam is a liquid taken by mouth, or via a gastronomy tube for people who can’t swallow. It’s thus more familiar to doctors and payers than a one-time gene therapy (AVXS-101) that could cost millions of dollars—Novartis has said a $4 million price tag would be justified, given its benefits—or a complex spinal injection (nusinersen) that costs $750,000 for the first year and $375,000 each one thereafter.

Roche, of course, has to prove that risdiplam can hang with its two rivals. Nusinersen has by far the most extensive body of data, followed by AVXS-101. Risdiplam has produced encouraging early data from the trials FIREFISH, in Type 1 patients, and SUNFISH, in Type 2 and 3 patients. The same trials will produce more substantial information next year, and strong data could prompt Roche to ask for FDA approval in 2020. Two more studies—JEWELFISH(patients who have been treated with other SMA drugs) and RAINBOWFISH (pre-symptomatic patients)—have started, or soon will.

Disease Area: Sickle cell disease

Company: Global Blood Therapeutics

Trial: HOPE (Part A)

Data Expected: 2019

Why We’re Watching: Genome-altering medicines, like the one noted above and this one, could one day fix the mutated gene that produces sickle cell disease. But complicated biology, health economics, and other factors make that prospect highly speculative. Even in a best-case scenario, gene therapies are years away.

Meanwhile, roughly 100,000 people in the U.S., predominantly African-American, and millions more around the world with the disease need relief now. Sickle cell’s telltale malformed red blood cells clog vessels and can’t carry enough oxygen to muscles and other tissues. Patients can suffer bouts of excruciating pain that often force hospital visits, as well as strokes, organ damage, and even with the best treatment, an early death.

The new drug closest to market is voxelotor from Global Blood Therapeutics (NASDAQ: GBT), a once-a-day pill that targets a key blood protein, hemoglobin, and aims to prevent red blood cells from bending into the malformed sickle shape. GBT has reported interim results from the first portion (Part A) of a Phase 3 study called HOPE, and they showed the drug’s ability to meaningfully boost hemoglobin levels, compared to placebo.

Data from Part B of HOPE were supposed to come next and include results from patients reporting their own daily conditions on a smart phone app, but those plans were scuttled in June, as Xconomy reported. GBT said the data were too hard to read.

Despite those big changes in the structure of HOPE, GBT believes voxelotor is on the cusp of being just the third drug ever approved to treat sickle cell. Investors believe it, too. They sent shares soaring two weeks ago during the ASH meeting after the company said that the FDA only needed the Part A data, detailing the hemoglobin boost, to make a faster-than-normal approval decision.

So what’s to watch in 2019? Investigators updated the Part A data at ASH, and the results continued to impress. But GBT only reported data from about half the 270 patients planned for the study. A fuller data set will provide a clearer picture of voxelotor’s ability to reduce pain episodes. The more comprehensive results should also help assess safety, which has yet to be an issue with voxelotor.

Those updates are important. While sickle cell can be life-threatening—severity can depend on genetic profile and other factors—many patients have learned to manage their conditions and are not in imminent danger. The balance between risk and benefit could be tricky to navigate if safety problems emerge as the trial expands. “Oral therapies are less risky and more appealing to me than transplant and gene therapy,” says Cassandra Trimnell, a sickle-cell advocate and patient whom Xconomy profiled earlier this year. “I’m not in and out of the hospital like other people.”

Disease: Cystic fibrosis

Company: Vertex Pharmaceuticals

Trials: NCT03525548, NCT03525444

Data expected: 1Q 2019

Why We’re Watching: Vertex has already brought drugs to market that, for about 40 percent of patients with cystic fibrosis, can change the course of the deadly genetic lung disease. If it’s to expand its franchise to reach about 90 percent of patients and hold off the emerging competition, data expected shortly could be key.

Early this decade, Vertex emerged from a humiliating loss in the hepatitis C competition and reinvented itself around cystic fibrosis. In 2012, the FDA approved ivacaftor (Kalydeco), the first drug to address the cellular malfunction underlying CF. But ivacaftor only helps roughly 5 percent of CF patients with specific genetic mutations, meaning the vast majority of those with the disease don’t benefit from the drug. The company has been steadily pushing that number upwards by combining ivacaftor with other in-house CF drugs. After ivacaftor came ivacaftor/lumacaftor (Orkambi), in 2015, and then ivacaftor/tezacaftor (Symdeko) in 2018. Revenue from the three drugs generated $784 million last quarter alone for Vertex, whose shares are currently trading near all-time highs.

But competition is coming, and with memories of the hepatitis C debacle still fresh, Vertex needs to stay a step ahead. To do so, it is testing two three-drug cocktails that could potentially address up to 90 percent of CF patients. Once the data are in, Vertex will take the better combination to the FDA.

Good Phase 3 results are already in for one combination (VX-659/ivacaftor/tezacaftor), raising the bar for future competitors such as AbbVie (NYSE: ABBV) and Proteostasis Therapeutics (NASDAQ: PTI), Raymond James analyst Laura Chico noted recently. (Proteostasis should have data from an early study of its own three-drug combination shortly.)

We’ll see how high the bar goes early next year, when Vertex divulges Phase 3 results for the second three-drug regimen (VX-445/ ivacaftor/tezacaftor). Vertex expects to file an approval application for the better of its triplets by mid-2019.

Disease Area: Cancer/Infectious diseases

Company: Moderna

Trials: NCT03313778, NCT03370887, NCNCT03313778, NCT03392389

Data Expected: 2019

Why We’re Watching: After much hype and mystery about its messenger RNA drugs—an unproven technology with enormous potential—Moderna has finally gone public, sporting an $8 billion-plus valuation, and with it a chance to see how much substance is behind the hype.

Moderna has 10 drugs in human testing, including vaccines for infectious diseases or cancer. Some of them could produce their first data next year, according to clinicaltrials.gov. These updates won’t make or break Moderna, but they should offer glimpses into its technology. And that’s worth watching. Moderna has reported some clinical data before, but not as a public company closely scrutinized by analysts and investors. Every incremental update will help prove whether the company is, or isn’t, for real.

Further afield are the results from Moderna’s most advanced program, an experimental mRNA therapeutic for coronary heart disease called AZD8601. It’s the only Moderna drug in Phase 2 testing, and is owned by AstraZeneca (NASDAQ: AZN), which was the first big drug maker to buy into Moderna with a 2013 partnership.

AZD-8601 is a synthetic mRNA molecule meant to boost the production of a protein called VEGF-A, which stimulates blood vessel growth. The hope is that more VEGF-A will help people with cardiovascular disease regenerate heart tissue by improving blood flow. A Phase 1 study of AZD-8601 in men with type 2 diabetes showed that treated patients produced more VEGF-A than placebo and had better blood flow. In Phase 2, up to 33 patients are getting the drug injected into their hearts during coronary artery bypass surgery. Results could come in 2020, according to clinicaltrials.gov.

Other companies’ mRNA updates are also expected next year, adding to the early body of evidence for this new type of medicine. Translate Bio (NASDAQ: TBIO), which bought Shire’s old mRNA technology, is in the midst of a Phase 1/2 study for cystic fibrosis; interim data are expected in the second half of 2019. CureVac is running two Phase 1 trials, one for an immunotherapy for solid-tumor cancers and another for a rabies vaccine. And Germany’s BioNTech should have Phase 1 data next year for two cancer vaccines, for melanoma and triple-negative breast cancer.

https://xconomy.com/national/2018/12/18/15-for-19-key-clinical-data-to-watch-for-next-year-part-2/?single_page=true