Denali Has Positive Results from Program for Parkinson’s

Denali Therapeutics Inc. (NASDAQ: DNLI) Wednesday announced positive results from its Phase 1 clinical study with DNL201, a small molecule inhibitor of leucine-rich repeat kinase 2 (LRRK2).

In a randomized, double blind, placebo-controlled, oral dose study in healthy subjects, DNL201 achieved its safety, pharmacokinetic, and pharmacodynamic objectives. DNL201 was generally well tolerated with no serious adverse events at doses that achieved high levels of cerebrospinal fluid (CSF) exposure, robust target engagement as measured by two blood-based biomarkers of LRRK2 activity, and effects on biomarkers of lysosomal function.

Mutations in the LRRK2 gene are the most frequent genetic cause of Parkinson’s disease and a major driver of lysosomal dysfunction, which contribute to the formation of Lewy body protein aggregates and neurodegeneration. LRRK2 regulates lysosomal genesis and function, which is impaired in Parkinson’s disease and may be restored by LRRK2 inhibition, thereby potentially positively modifying disease progression in patients with a genetic LRRK2 mutation as well as in patients with sporadic Parkinson’s disease.

In the study of DNL201, more than 100 healthy subjects, including healthy elderly subjects, received either single or multiple ascending doses or placebo. Based on the clinical data from this study, Denali intends to advance DNL201 into a Phase 1b clinical study in Parkinson’s disease patients with and without a genetic LRRK2 mutation by year-end 2018. Detailed clinical data from the Phase 1 study with DNL201 will be presented at a future medical conference.

“We conclude from this clinical trial that DNL201 was able to achieve the targeted level of LRRK2 inhibition at doses that were safe and well tolerated. We are pleased that the trial was a success in all these key measures. The trial data give us confidence to proceed with further clinical testing in Parkinson’s patients and provide a solid basis for selection of the optimal dose for future clinical trials in patients,” said Carole Ho, M.D., Chief Medical Officer.

“We are leading the way in testing LRRK2 inhibitors in humans with the goal of bringing a disease modifying therapeutic to patients suffering from Parkinson’s disease,” said Ryan Watts, Ph.D., CEO. “We are also encouraged to see mounting evidence supporting a role of LRRK2 inhibition in the broader sporadic Parkinson’s disease population, in addition to Parkinson’s disease genetically associated with a LRRK2 mutation.”

A Phase 1 dose escalation study with DNL151, a second small molecule inhibitor of LRRK2, is ongoing in the Netherlands.

https://bit.ly/2Oz7Ejz

Humana eyes stronger ties with Walmart despite Walgreens partnership

Humana Inc (NYSE: HUM) said it was looking to expand its tie-up with Walmart (NYSE: WMT), easing concerns that the insurer’s agreement with drugstore chain Walgreens Boots Alliance (NASDAQ: WBA) would prevent it from broadening its partnership with the retailer.

Humana’s shares rose about 4 percent to a record high of $326.97 after Chief Executive Bruce Broussard’s comments on a call discussing the company’s better-than-expected earnings.

“We still value and have a strong relationship with Walmart,” Broussard said, adding that the insurer is looking at ways to expand the partnership.

Walmart currently has a co-branded Medicare drug plan with Humana that steers patients to Walmart stores. The partnership offers a prescription drug plan that can save up to 20 percent in drug costs for customers.

In June, the insurer announced it would partner with Walgreens, with its unit operating senior-focused primary care clinics inside two Walgreens stores in Kansas, a move some analysts said at the time ended any speculation over a deal with Walmart.

Reuters reported in March that Walmart was in early talks with Humana about developing closer ties, with a possible acquisition on the table.

“Both of them (ties to Walmart and Walgreens) are complementary,” Broussard said, adding partnering with one does not restrict the other deal.

Unlike its rivals, Humana has said it will focus on partnerships and smaller deals while cementing its dominance in the Medicare Advantage business, which powered a better-than- expected second quarter profit.

Humana, in the past few months, has joined hands with private equity firms to buy health care services companies, creating the largest hospice operator in the United States.

RAISES FORECAST

Humana also raised its 2018 adjusted earnings forecast to about $14.15 per share from its previous forecast of $13.70 to $14.10 per share.

The company’s adjusted consolidated benefit ratio, the percentage of premiums spent on claims, deteriorated to 84.3 percent in the quarter, missing consensus estimate of 83.9 percent according to brokerage Evercore ISI.

Over the past few quarters, insurers have kept a tight leash on medical costs and even a slight slip has weighed on stocks.

Earlier this month, the largest U.S. health insurer UnitedHealth Group (NYSE: UNH) reported quarterly medical costs slightly higher than expected, overshadowing a second quarter profit beat.

Excluding items, Humana earned $3.96 per share, beating analysts’ average estimate of $3.77, according to Thomson Reuters I/B/E/S.

Revenue rose 5.4 percent to $14.26 billion, above the average estimate of $14.16 billion.

https://bit.ly/2Mc4Nvl

Use of prescription opioids in U.S. remains high

Use of prescription opioids remains high in the U.S., despite public health efforts and growing awareness of risks for abuse and overdose, a new study suggests.

Over a decade, the proportion of adults being prescribed opioid medications has changed little, but dosages have continued to rise and are especially high among patients with permanent disability, researchers report in The BMJ.

That was surprising to study leader Molly Moore Jeffery of the Mayo Clinic in Rochester, Minnesota. “You expect to see them using more, but it was bigger than I expected,” she said.

The dosages are concerning because they were higher than the “point where you see a greater risk of overdose,” Jeffery said.

Also concerning were the number of patients with prescriptions for both opioids and benzodiazepines, because the combination can raise the risk of death, Jeffery said.

The U.S. has the highest per capita rate of opioid use in the world – nearly double that of second-ranked Germany and seven times higher than the UK, the researchers note. On average, 40 people die in the U.S. daily from prescription opioid overdoses, a four-fold increase since 1999, they add.

Jeffery’s team analyzed a national database of medical and pharmacy claims to examine trends in opioid use among 48 million people with health insurance between 2007 and 2016. They included working-age adults with commercial insurance, as well as Medicare beneficiaries eligible for coverage either because they were over age 65 or younger but disabled.

Overall, 14 percent of commercially insured patients and 26 percent of older Medicare beneficiaries used opioids during the study period. The rate was 52 percent among disabled Medicare beneficiaries.

To allow comparisons between different opioid medications, the researchers converted all prescription doses into so-called milligram morphine equivalents (MME).

Like other recent studies, this one showed that opioid use and average dose leveled off after peaking in 2012-2013. But the MME dose in all groups of patients was still higher in 2016 than it was in 2007.

“All reports are showing that opioid prescribing still occurs too frequently and (is) far higher than in the 1990s in the U.S.,” said Dr. John Mafi of the David Geffen School of Medicine at the University of California, Los Angeles, who wasn’t involved in the study. “This is a cause for alarm and we need rapid and effective policy changes to decrease overprescribing and reduce opioid-related deaths. Specifically, we need to improve access and coverage of evidence-based non-opioid pain alternatives, such as topical non-steroidal anti-inflammatory medications for acute musculoskeletal pain or physical therapy for chronic low back pain.”

Still, doctors need to proceed with caution in people with chronic pain, Mafi said. Limiting opioids too strictly can put an undue burden on patients in severe pain. Changes need to allow autonomy for doctors and only target patients at the highest risk for overdose, he added.

That’s especially true for the disabled patients, many of whom suffer from multiple serious medical problems, said Dr. Ajay Wasan, vice chair for pain medicine in the department of anesthesiology at the University of Pittsburgh Medical Center, who wasn’t involved in the study.

“You should not assume all opioid prescribing is bad,” Wasan said. “Those with high levels of disability because of severe musculoskeletal disorders might have severe pain. There’s a long history of pain being poorly treated in this country. The goal shouldn’t be to get back to 2007 levels. The goal should be to make sure there are good prescribing practices and appropriate monitoring.”

Moreover, the pattern of the opioid epidemic has changed, Wasan said. In the past, many people were introduced to opioids through prescription medications, but now the epidemic is “really dominated by heroin and other illegal drugs,” he noted.

Jeffery didn’t know whether rules implemented recently by insurance companies and others to reduce opioid prescriptions have had any effect. But, she said, legislation isn’t the way to go.

Noting that Medicare Advantage has floated the idea of limiting payments for higher dose prescriptions, she said, “I don’t think the answer is to either criminalize or put administrative barriers up.”

SOURCE: bit.ly/2LKaRPv The BMJ, online August 1, 2018.

https://reut.rs/2Mf6yIc

BeiGene raises $903 million in HK’s first secondary listing under new rules

Chinese Nasdaq-listed biotech BeiGene Ltd has raised $903 million after pricing its secondary listing in Hong Kong – the first under new exchange rules – near the top of an indicative range, three people close to the deal said on Thursday.

The listing comes as Hong Kong works to lure overseas-listed firms to conduct secondary share offerings in the financial hub. It is also the second listing under new rules for early-state drug developers.

Hong Kong’s stock exchange is seeking to establish itself as a financing center for the growing number of pre-revenue drug developers. Its efforts will pit it against Nasdaq, currently the biggest center for biotech listings, with $2.4 billion worth of such shares sold last year, Thomson Reuters data showed.

BeiGene, which develops molecularly targeted and immuno-oncology drugs to treat cancer, is selling 65.6 million new shares, or 8.55 percent of its enlarged share capital, at HK$108 ($13.76) each, close to the top of a price range of HK$94.4 to HK$111.6, the people said.

The price of its secondary listing represents a discount of 1.6 percent against its closing price of $181.74 in the U.S. on Wednesday.

BeiGene has seen its shares jump more than seven times since raising $158 million in its 2016 Nasdaq IPO. Each American Depository share (ADS) represents 13 ordinary shares.

BeiGene declined to comment on the pricing. The people declined to be identified as the information was not public.

Four cornerstone investors – Singapore sovereign wealth fund GIC Pte Ltd [GIC.UL], U.S. hedge fund Baker Brothers Advisors and Chinese investment firms Hillhouse Capital Group and Ally Bridge – have committed $276 million for the offering.

Under Hong Kong’s new rules, in place since April 30, biotech firms without revenue or profit can apply to list.

The first listing by Ascletis Pharma Inc under the new listing regime saw shares close flat with their IPO price on their debut on Wednesday.

More than 10 biotech firms – mostly Chinese and including Innovent Biologics, backed by Singapore state investor Temasek Holdings (Pte) Ltd [TEM.UL], and Shanghai Henlius Biotech – plan to list in Hong Kong and some have dropped U.S. IPO plans in favor of listing closer to home.

“There are a lot of global investors that are specialists in biotech, but they know very little about China. And there are a lot of investors (here) that know a lot about China, but they know very little about biotech. The dual-listing that we’re doing is helping educate both ways,” John V. Oyler, founder and chief executive of BeiGene, told a news conference in Hong Kong on Sunday.

The China and U.S.-based BeiGene was founded by Oyler and Wang Xiaodong in 2010. It has a portfolio of six internally developed clinical drug candidates including three near commercial stage, its prospectus showed.

It plans to use proceeds from its secondary listing for developing and commercializing the three late-stage drug candidates, expanding its product portfolio and for general working capital, the prospectus showed.

The company recorded a net loss of $105 million in the first quarter of 2018, a loss twice as wide as in the same period a year prior.

Its shares will start trading in Hong Kong on Aug. 8.

Goldman Sachs and Morgan Stanley are joint sponsors for the deal.

https://reut.rs/2Mc0QXt

Molson Coors to make cannabis-based drinks in Canada

 Molson Coors Brewing Co Canadian arm will make cannabis-infused drinks along with marijuana producer Hydropothecary Corp, betting on a promising market as beer sales stagnate in North America.

The brewer is the latest to capitalize on Canada’s decision to legalize recreational marijuana later in the year, a market industry watchers say could be worth $5 billion to $10 billion.

Last year, Corona beer-maker Constellation Brands Inc became the first major beer and spirits producer to partner with a Canadian marijuana producer, picking up a nearly 10 percent stake in Canopy Growth Corp.

Molson Coors Canada said its joint venture with Hydropothecary, which will make non-alcoholic pot-based drinks, will be a standalone company with its own board of directors and an independent management team.

The deal is expected to close before Sept. 30, just ahead of the proposed legalization of recreational marijuana in Canada. Marijuana products like toffees and drinks are expected to be legalized by 2019.

The Canadian brewer will have a 57.5 percent controlling interest in the venture, with Hydropothecary owning the rest.

Molson Coors, the No. 2 beer maker in North America, has seen global beer volumes fall in the latest quarter. In the United States, volumes dropped 4.8 percent as consumers shift to craft beers and wine.

“There is a paradigm shift underway and cannabis has the potential to provide answers to the alcoholic drinks industry’s existential questions,” said Spiros Malandrakis, head of alcoholic drinks at Euromonitor.

https://bit.ly/2LLGDvl

Fitbit posts smaller loss on strong smartwatch sales

Fitbit Inc on Wednesday outpaced Wall Street estimates for quarterly results as its strategy of adding smartwatches to its product line got a boost in the second quarter with higher sales for ‘mass-appeal’ Versa.

Smartwatch sales in the second quarter accounted for about 55 percent of its total revenue of $299.3 million (227.97 million pounds), which beat estimates of $285.4 million.

Shares of the company rose 3 percent to $6.11 in after-hours trading, with the company selling a total of 2.7 million devices in the quarter, above FactSet’s average estimate of 2.5 million.

Fitbit, which is popular for its colourful fitness trackers, is a late entrant to the smartwatch market and has been facing stiff competition from tech players with deeper pockets such as Apple Inc and Samsung Electronics.

Versa smartwatch outsold Samsung, Garmin and Fossil smartwatches combined in North America in the quarter, Chief Executive Officer James Park said in a statement.

Earlier in the day, rival Garmin Ltd reported better-than-expected quarterly profit, signalling higher demand in the wearable devices market.

Fitbit, which makes use of Chinese contract manufacturers to produce most of its devices, said if the proposed U.S. tariffs on Chinese goods comes into effect, it would impact its material costs.

“We are navigating a number of different paths to reduce or eliminate the impact of the tariff,” Chief Financial Officer Ronald Kisling said on a conference call with analysts.

The company said its full-year revenue forecast of $1.5 billion excludes the impact of the proposed U.S. tariffs on $200 billion worth of Chinese goods.

Fitbit now expects third quarter revenue in the range between $370 million and $390 million, the midpoint of which was above the average analyst estimate of $377.6 million.

The company’s net loss widened to $118.3 million, or 49 cents per share, in the second quarter ended June 30 from $58.2 million, or 25 cents per share, a year earlier.

On an adjusted basis, the company lost 22 cents per share, smaller than the estimate of 24 cents, according to Thomson Reuters I/B/E/S.

https://bit.ly/2LNzScz

Updated Staffing Data Lowers Ratings for Many Nursing Homes

Star ratings for staffing levels at nearly 1,400 nursing homes across the United States were lowered by Medicare when updated ratings were released on July 25.

The changes for about one in 11 nursing homes nationwide were made because they had too few registered nurses or did not provide payroll data proving they had required nursing coverage, The New York Times reported.

The revised staff ratings gave one star out of possible five to 1,387 of the nation’s 15,616 skilled nursing facilities. The lowered star ratings for staffing are disappointing and largely due to a shortage of workers, according to Katie Smith Sloan, president of LeadingAge, an association of nonprofit providers of aging services, including nearly 2,000 nursing homes, The Times reported.

Medicare uses a five-star rating system to help families select a nursing home. The ratings are on the federal government’s Nursing Home Compare website. On the website, Medicare said the nursing homes with a one-star staffing rating either lacked a registered nurse for “a high number of days” over three months, provided unverifiable payroll data, or didn’t supply any payroll data, The Times reported. Medicare requires every nursing home to have a registered nurse working at least eight hours every day.

The New York Times Article
Nursing Home Compare

https://bit.ly/2LKOBon