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Monday, July 1, 2019

Celyad to advance CYAD-02 into the clinic

Celyad (NASDAQ:CYADannounces that the FDA has signed off on its IND for its next-generation CAR-T candidate CYAD-02 clearing the way for clinical trials in relapsed/refractory acute myeloid leukemia (AML). Enrollment in a Phase 1 dose-escalation study should commence in early 2020. The company says CYAD-02 is based on licensor Horizon Discovery’s optimized shRNA SMARTvector technology.
In a Phase 1 trial, first-generation CYAD-01 showed “preliminary anti-leukemic activity” in 46% (n=6/13) of AML patients. Preliminary data from cohort 4 should be available by year-end.
Management will host a conference call tomorrow, July 2, at 8:00 am ET to discuss its plans.

States explore importing drugs. Will it catch on?

Seeking a solution to the soaring costs of drugs, Colorado, Florida and Vermont are making plans to import medications from Canada, where prescriptions are cheaper.
President Donald Trump has offered his support, marking the first time drug importation has won a presidential endorsement.
The states’ plans are in their infancy. But they signal how frustration among consumers—especially those shouldering greater portions of their healthcare bills through high-deductible health plans—is putting pressure on federal and state officials.
Because so many details are still being hashed out, it’s not yet clear who would be helped by the states’ efforts or if the plans can ultimately gain federal approval and withstand likely court challenges.
In the early 2000s, attempts by a few states, led by Illinois, to allow drug importation fizzled, and any new plan faces stiff regulatory and legal hurdles. But drug prices are at an all-time high. The increasing popularity of high-deductible plans means a growing number of patients are spending more money on healthcare. And Trump’s endorsement and current consumer demand for lowering drug prices could yield a different result this time around.

“Everyone is eager to get going into uncharted territory,” said Trish Riley, executive director of the National Academy for State Health Policy, a nonpartisan group of state health officials, which has been working with Vermont on its importation plan.
Gabriel Levitt, president of PharmacyChecker.com, which verifies online foreign pharmacies for customers, said the high prices for drugs make the efforts worth pursuing.
“It certainly will be helpful to reduce costs for some in the states that go ahead, and that’s a great start,” he said. Plus, he added, Trump’s support “puts the wind at the sails of importation.”

Tempering expectations

The 2003 Medicare Modernization Act allows states to import cheaper drugs from Canada, but only the Health and Human Services secretary verifies their safety. Previous attempts by states to allow importation failed because the secretary opposed them.
Vermont, Florida and Colorado plan to work together to set up a program to buy drugs from Canada, said Riley. That coalition of states—with governors from the center, right and left—shows how powerful the issue of high-priced drugs is with voters.
The same medicines are often cheaper in other countries than in the U.S. since most developed countries negotiate with drugmakers to set prices.
State officials said they expect that the effect of their programs would be modest to start, generally first permitting the importation of only certain types of high-priced drugs and for specific populations.
For example, infusion medicines used for cancer or autoimmune diseases that are administered in medical offices would not be available to import from Canada under the programs the states are setting up. Nor would drugs such as insulin, which needs to be refrigerated. Prices for these types of drugs have come under fire in the U.S., with patients calling them unaffordable.
“It’s a few states and a few drugs,” Riley said.

No tampering with safety

Vermont, which passed legislation to start planning the program a year ago, is still trying to find a way to ensure the safety of imported drugs and so far has identified only 17 medicines that would save enough money to be worth bringing over the border. Those drugs include treatments for conditions including diabetes, hepatitis C, cancer and HIV/AIDS.
After a review, officials decided it was not worth importing drugs for Medicaid enrollees because the state already receives hefty rebates on those medications from U.S. manufacturers and patients do not have copayments. So Vermont’s program is being designed to help residents who have commercial insurance.
Florida’s legislature authorized a blueprint this spring with a strong endorsement from Republican Gov. Ron DeSantis. The program aims to help bring down drug costs for the Medicaid program, which covers the more than 4 million enrollees in the state, prisoners and patients at free health clinics. The legislature also authorized a separate program that would provide drugs for individual Florida residents.
DeSantis signed the bill June 11 and called on federal officials to “get this done.”

Colorado approved its legislation in May, but state officials said they do not yet have details on what it might cover.
Officials in all three states have high hopes that the programs will succeed in ways not possible the last time around.
Between 2004 and 2009, Illinois, Kansas, Missouri, Rhode Island and Vermont defied the federal government and allowed residents to import from a Canadian retail pharmacy under a joint program, which flopped. Just 5,000 people participated, far fewer than the millions predicted, partially because the federal government declared the program violated federal law and warned against using the drugs. Also, in 2006, it established a Medicare drug benefit to help those 65 and older, further weakening demand.
Besides, after several years, the Canadian health minister threatened to prohibit pharmacies from participating over concerns that the program might cause shortages, and the main Canadian supplier pulled out due to lack of demand.
In 2014, Maine briefly allowed residents and employers to buy foreign drugs. Under that law, some employers, including the city government of Portland, established a program for workers to use CanaRx, a Canadian company that connects customers with brick-and-mortar pharmacies in Canada, Great Britain and Australia.
After pharmaceutical manufacturers and pharmacists sued, a federal judge overturned the law in early 2015, citing its conflict with federal law.

Then and now, opponents of importation say sending drugs over the border will increase the chances Americans get counterfeit medications, a claim often boosted by the drug industry. Levitt noted that states now intend to work directly with and inspect Canadian wholesalers, which should make Americans more comfortable about drug safety.
With prices so high, individual Americans are more open to buying drugs from Canada, anyway—some have for decades been driving over the border, using online pharmacies or going into storefronts that connect buyers to pharmacies in Canada and other countries. Although these strategies are technically illegal, the government does not prosecute individual offenders. Nor has it moved to stop the dozens of cities, counties and school districts across the United States that have programs for employees to buy drugs from Canada and other countries.
Canadian health officials are watching the debate and said they are weighing the effect a robust importation program would have on Canadian consumers.
“Collaborative efforts among implicated parties would be important in addressing any potential adverse impacts on the drug supply in Canada that may arise from increased cross-border trade,” said Eric Morrissette, a spokesman for Health Canada, the government agency responsible for public health.

Carpal Tunnel Syndrome: ‘Red Flag’ for Subsequent ATTR, Heart Failure

Carpal tunnel syndrome may be an early warning sign of amyloidosis and heart failure, a Danish study showed.
Matched by age and sex to the general population, people who got carpal tunnel surgery had higher risks of developing amyloidosis (0.10% vs 0.006%, adjusted HR 12.12, 95% CI 4.37-33.60) and heart failure over the next 10 years (5.3% vs 3.2%, adjusted HR 1.54, 95% CI 1.45-1.64).
These patients also experienced significantly more of other adverse cardiovascular outcomes — such as atrial fibrillation, atrioventricular heart block, and pacemaker implantation — according to a group led by Emil Fosbøl, MD, PhD, of the University Hospital of Copenhagen, Rigshospitalet, reporting in the July 9 issue of the Journal of the American College of Cardiology.
Given that the absolute incidence of diagnosed amyloidosis was still low for either group, carpal tunnel syndrome by itself “may not merit direct referral for further evaluation for amyloidosis, but could rather be considered a red flag and an opportunity for early disease detection,” Fosbøl and colleagues said.
“Transthyretin cardiac amyloidosis is still usually found too late, when severe left ventricular thickening, restrictive cardiomyopathy, and depressed systolic function can lead to orthostasis, hypotension, conduction disease, dyspnea, and death. To improve outcomes and start drugs when they can be of benefit, early diagnosis of transthyretin cardiac amyloidosis is imperative,” commented Van-Khue Ton, MD, PhD, and colleagues, all from the University of Maryland School of Medicine in Baltimore, in an accompanying editorial.
Study investigators also found that the subgroup with heart failure and a history of carpal tunnel syndrome showed lower short-term but higher long-term mortality risk than peers with heart failure but not the latter — consistent with the development of wild-type transthyretin cardiac amyloidosis, they said.
Their study was based on Danish registry data spanning from 1996 to 2012 (total of 56,032 patients). Median age was 53.9 years and 67.9% of the cohort were women.
Carpal tunnel syndrome is known to be common in transthyretin amyloidosis (ATTR), and the two may be linked by systemic amyloid accumulation. On top of that, ATTR has been found to be one of the causes of heart failure with preserved ejection fraction (HFpEF), according to the authors.
“It would be highly interesting to determine the importance of HFrEF [heart failure with reduced ejection fraction] versus HFpEF in the current study, but unfortunately, these data were not available in the registry,” Fosbøl’s group acknowledged. “It is crucial that future studies phenotype the HF syndrome associated with CTS [carpal tunnel syndrome].”
Other limitations of the study include its observational nature and the lack of certain clinical variables in the files (for example, hereditary amyloid cardiomyopathy and wild-type ATTR could not be distinguished from the dataset).
Moreover, people who got surgery for carpal tunnel syndrome had more comorbidities than controls and were on more medications, especially anti-inflammatory drugs, at baseline.
“[C]arpal tunnel syndrome often predates clinical amyloidosis by decades. Thus, a 10-year study, while admirable, might still miss many patients with amyloidosis. Furthermore, amyloidosis is still underdiagnosed, and true rates might be much higher,” Ton and colleagues added.
ATTR cardiomyopathy also presents more commonly in men and non-Caucasians, suggesting that the Danish population may not be the best group in which to study this, the editorialists wrote.
With such low absolute event rates in patients with carpal tunnel syndrome in the present study, the question is whether it would only predict relatively few amyloidosis patients, the editorialists said.
Nevertheless, they agreed that carpal tunnel syndrome could be considered a “red flag” of possible amyloidosis down the road.
Fosbøl and Ton disclosed no conflicts of interest.

Recent IPOs show investor appetite is strong for biotechs

Investor appetite is strong for biotechs. Adaptive Biotechnologies (ADPT) is up on its second day of trading, after soaring more than 95% yesterday. The Seattle-based company, founded in 2009, reads and translates genetic code to develop personalized diagnostics and therapeutics for patients.
The company’s long-term vision is to become an integral part of primary care. ”You go in once a year, you get your blood drawn, we you look at your immune system. And we diagnose many diseases at one time,” said CEO and co-founder Chad Robins.
Microsoft (MSFT) is an investor in the company, which Robins describes an immune medicine information platform. “It’s a convergence play between a kind of biotech, and technology and machine learning with our Microsoft collaboration.”
Adaptive Biotechnologies currently has two commercial products used by researchers and pharmaceutical companies. One is a tool for monitoring minimal residual disease in certain blood cancers. “We can look at whether a drug has worked or not on the patient. And next we can determine whether that patient is potentially going to relapse from a molecular level before they relapse clinically, before they go into a doctor’s office and present with symptoms,” said Robins.

Biotech market

On the same day Adaptive went public, so did Change Healthcare (CHNG), Morphic Holdings (MORF), and BridgeBio Pharma (BBIO), which opened more than 80% above its IPO price.
BridgeBio Pharma focuses on medicines targeting diseases that arise from defects in a single gene, as well as cancers with clear genetic drivers.
“Most diseases are just black boxes, you don’t understand what’s going on,” CEO Neil Kumar told Yahoo Finance. “For the diseases we go after it is very clear, it is that single mutation, and what that enables us to do is to say, how do we counteract exactly what that mutation is doing,” he added.
BridgeBio Pharma highlights that rather than investing in one drug, the company is focusing on 15 development programs, which fall into three categories: Mendelian, Oncology and Gene Therapy.
As with a number of unicorns this year, Morphic, Adaptive Biotechnologies and BridgeBio Pharma fall into the ‘not profitable yet’ category.
Even though BridgeBio Pharma has not generated revenue from product sales, Kumar says his company has a timeline. “Certainly the only way to build something that’s reasonable and sustainable is to get to the point where you have commercial products, where you’re really making a difference for patients,” said Kumar. “Having cash flowing products, I think is a big deal and I think we should be able to get there in the next four to five years,” he added.
Despite the warm IPO reception and recent biotech acquisitions, overall market performance in biotech has lagged the S&P (^GSPC). Biotech companies in particular run the unpredictable risk of trials which may or may not meet endpoints. Earlier this year Biogen (BIIB) plunged 25% when it discontinued its clinical trial for an Alzheimer’s treatment.

Codiak BioSciences withdraws IPO

Citing market conditions, Codiak BioSciences (CDAK) has withdrawn its planned IPO.

FDA OKs Foundation Med’s FoundationOne CDx Lynparza companion

The FDA has approved Roche (OTCQX:RHHBY +0.7%) unit Foundation Medicine’s FoundationOne CDx molecular test as a companion diagnostic for AstraZeneca’s Lynparza (olaparib) for first-line maintenance therapy in BRCA mutation-positive ovarian cancer.
The companies and Merck are also collaborating on developing companion diagnostics for Lynparza in prostate cancer.

Teva launches 1% sodium hyaluronate in U.S.

Teva Pharmaceutical Industries (NYSE:TEVAcommences the U.S. commercial launch of 1% sodium hyaluronate for the treatment of pain associated with osteoarthritis of the knee in patients who have failed to adequately respond to non-drug therapy and simple painkillers (e.g., acetaminophen).