Alexion: Positive Topline Results in Phase 3 Myasthenia Gravis Study

 Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced positive topline results from a Phase 3 study evaluating the safety and efficacy of ULTOMIRIS® (ravulizumab-cwvz) in adults with generalized myasthenia gravis (gMG). The study met, with high statistical significance, its primary endpoint of change from baseline in the Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score, a patient-reported assessment, at Week 26, and for the subset of patients who have completed 26 weeks in the extension study to date, the positive treatment effect was maintained through a total of 52 weeks. ULTOMIRIS was well tolerated with a safety profile consistent with that observed in Phase 3 studies in paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). Based on these results, Alexion plans to make regulatory filings in the U.S., European Union and Japan in late 2021/early 2022.

“The treatment landscape for people living with gMG has advanced and expanded rapidly in recent years, empowering both patients and caregivers. However, as a clinician and scientist, I know the work is not done,” said Professor James F. Howard, M.D., Department of Neurology at The University of North Carolina, Chapel Hill, USA, and lead primary investigator in the Phase 3 study. “These Phase 3 ULTOMIRIS results reinforce the critical role complement inhibition plays in treating gMG. I am encouraged by the opportunity this could provide for more patients to be treated early with a mechanism of action designed to preserve neuromuscular function.”

“The approval of SOLIRIS was a critically important first step in addressing the urgent need for a treatment for people with severe symptoms and complications of MG, and was the first new treatment for this devastating disease in more than 60 years. Today’s results demonstrate that ULTOMIRIS may help a broader range of patients than was studied in the SOLIRIS Phase 3 trial, including those with milder symptoms or earlier in their treatment journey, while still offering clinically meaningful benefits that were seen as early as Week 1 and maintained up to 52 weeks,” said John Orloff, M.D., Executive Vice President and Head of Research & Development at Alexion. “These data provide confidence that ULTOMIRIS has the potential to become the new standard of care for gMG and may reduce patient burden with its less frequent dosing schedule, leading to better treatment adherence and patient satisfaction. We are working to prepare regulatory submissions in the U.S., EU and Japan as quickly as possible.”

https://www.businesswire.com/news/home/20210715006015/en/Alexion-Announces-Positive-Topline-Results-from-Phase-3-Study-of-ULTOMIRIS%C2%AE-ravulizumab-cwvz-in-Adults-with-Generalized-Myasthenia-Gravis-gMG

Lawmakers urge NY to lift limits on nursing home visits

 Lawmakers are demanding that Gov. Andrew Cuomo lift remaining restrictions for visits at nursing homes, according to a letter sent by two dozen Democratic lawmakers to the governor this week.

New York lifted many restrictions on nursing home visits this spring in light of federal guidance that, in part, cleared the way for loved ones to hug residents if both are vaccinated.

Nursing homes in New York are urged to provide outdoor visits as well as indoor visits, though visits can still be curtailed once residents or staff test positive. Residents also can receive “compassionate care” visits that aren’t subject to restrictions for a variety of scenarios, including residents who are in end-of-life care.

But some nursing homes in New York are still only allowing one or two visitors at a time to visit loved ones for as little as 30 minutes once or twice a week, sometimes with hours limited to weekdays.

“In the year before vaccinations became available, our seniors endured loneliness and isolation that had very real impacts on their physical and mental health,” the lawmakers wrote in the July 12 letter to Cuomo. “Many still have not fully recovered. While the majority of New Yorkers have had the opportunity to resume a life of preCOVID-19 activity, seniors in many nursing homes have been excluded.”

Christina McComish, 59, of Valatie, said her 88-year-old mother has declined in the last year, and has struggled with isolation, dementia and hearing loss. McComish said it can take days to make appointments to see her mother for 30-minute long appointments at opposite ends of a dining table in the nursing home lobby.

She said she snuck a hug with her mother during their last visit, even though the nursing home discouraged it. McComish, who works as a creative arts therapist at another nearby nursing home, said it’s a struggle to know what visitation rights residents and family members have.

She said her mother’s nursing home has told her that compassionate care visits are only for “end-of-life” scenarios.

“She’s vaccinated, I’m vaccinated,” McComish said. “She’s just going to die in there, she’s just going to die alone.”

Sen. Rachel May, who pushed for a new law to allow limited visitation even in states of emergency, said she and other lawmakers are hearing from too many constituents who find it too difficult to visit loved ones at a time when New York has lifted the bulk of COVID-19 restrictions statewide as the state of emergency expired.

“Obviously states need to have control over out-of-control public health emergencies,” she said. “Barring that it seems to me that if your nursing home is your home you should have the right to visit your person and that should be pretty basic.”

New York’s Department of Health released updated visitation rules last week that said nursing homes can face citation and enforcement actions for restricting visitation without a “reasonable clinical or safety cause” under federal law.

But May said that guidance still gives nursing homes too much leeway.

The rules, for example, say that a nursing home’s visitation schedule should allow residents to receive visitors for their desired length of time.

But the state’s guidance also says that nursing homes should consider scheduling visits for a specific length of time to help ensure all residents can receive visitors while adhering to infection protocols, including providing six feet of social distancing.

It’s unclear whether nursing homes can be penalized in cases where visitation rules are too strict, and whether family members and loved ones have any recourse with the state if they think a nursing home isn’t following state and federal guidance. The Department of Health didn’t immediately respond Thursday to such questions from the Associated Press.

Nursing home residents, meanwhile, can seek help from the office of the State Long Term Care Ombudsman.

Meanwhile, New York U.S. Rep. Claudia Tenney is pushing a federal bill to allow residents of group homes — including nursing homes — to have limited visits during public health emergencies, as long as infection protocols are followed.

https://apnews.com/article/business-health-coronavirus-pandemic-nursing-homes-3a2ff854b2880ff8992fa3e38dfff898

QIAGEN NV: Gets a Buy rating from Berenberg

 In a research note published by Scott Bardo, Berenberg advises its customers to buy the stock. The target price is revised downwards from EUR 54 to EUR 50.

https://www.marketscreener.com/quote/stock/QIAGEN-N-V-40135659/news/QIAGEN-NV-nbsp-Gets-a-Buy-rating-from-Berenberg-35866472/

Merck details an immunotherapy 'milestone' in early breast cancer

 Merck & Co. is detailing for the first time proof that immunotherapy can stop tumors from returning in patients with an aggressive type of early-stage breast cancer, a finding that the drugmaker plans to use to rebound from a regulatory rejection in March.

Results from a late-stage study of 1,174 patients showed a combination of Merck's Keytruda and chemotherapy, given before surgery to remove a tumor and followed by immunotherapy alone after, led to a 37% reduction in the risk of cancer's return or death compared to only chemotherapy in people with triple-negative breast cancer.

After a median follow-up of just over three years, nearly 16% of patients who received Keytruda and chemotherapy had signs of disease progression, such as recurrence, the formation of a new type of tumor or death. That compared to about 24% who had received chemo alone and experienced one of these "events." Drugmakers like Merck measure "event-free survival" as a way to gauge whether their treatments might benefit patients with early-stage cancers.

Researchers reported about 85% of people given Keytruda and chemo in the study were event-free after three years, versus just under 77% of those on only chemo.

Merck has shared the data with the Food and Drug Administration. If approved, Keytruda could become the first immunotherapy available for patients with early-stage breast cancer.

"This is, in my opinion, a milestone," said Peter Schmid, the study's lead investigator and the chair of cancer medicine at Barts Cancer Institute at Queen Mary University London. Schmid has consulted for Merck and other cancer drugmakers.

Immunotherapies like Keytruda, Bristol Myers Squibb's Opdivo and Roche's Tecentriq are approved for many types of cancers that have already spread. Merck's trial is part of a push by the companies to use immunotherapies earlier, when they might stop cancers from returning and becoming more deadly. A few approvals have already been granted for immunotherapies administered after surgery. Several additional trials are underway, as well as tests of drug regimens that start even earlier, before the removal of a tumor.

These studies have sparked debate about the benefits immunotherapy can offer patients when given earlier, in part because drugmakers are using interim measures to get treatments to market before proving they can extend lives.

Merck, for instance, first tried to win approval of Keytruda in early-stage triple-negative breast cancer based on an improvement in pathological complete responses, or the disappearance of cancers from tissue samples. An FDA advisory panel voted against Keytruda, however, and recommended the agency wait until event-free survival data showed a benefit. The regulator rejected Keytruda for the indication in March.

But by May, Merck said it had positive data on that measure and on Thursday revealed the specific results, which are important given the high recurrence rates for patients with triple-negative tumors. One 2019 study estimated 40% of triple-negative patients with Stage 1 to Stage 3 disease eventually have their tumors return. Cancers become progressively more deadly when they return or take root in different organs.

While delaying cancer recurrence is viewed as a proxy for a drug's ability to keep patients alive longer, that hasn't always been the case. Some cancer doctors are critical of the measure and as a result have been hesitant to use immunotherapies in early disease settings. A snap poll conducted during ASCO, the year's biggest meeting for cancer research, found a majority of oncologists would wait for survival data before prescribing an immunotherapy.

Merck's trial, known as Keynote-522, hasn't run for long enough for investigators to definitively determine whether the Keytruda-chemo regimen can extend patients' lives. Results are trending in that direction, however, as investigators reported a 28% reduction in the risk of death versus the chemo arm. The comparison is not yet considered statistically significant.

Schmid expects that eventually a survival benefit will be clear. There is a "strong link," he said, between recurrence and survival in triple-negative disease, as patients' cancers often return within three years and can kill them within another two.

Researchers found about 7% of Keytruda patients had more lethal "distant" cancers return, compared to 13% on chemotherapy, a sign of increased survival chances. Positive results were reported across different patient subgroups, including among those who still had cancer on biopsied tissue after surgery and those whose tumors didn't express a protein linked to immunotherapy response, he added.

Side effects were more commonly observed with Merck's drug, particularly the immune-mediated complications often associated with immunotherapy, which occured in about twice the number of patients on Keytruda than chemo alone.

Keytruda was also associated with an increased rate of hypothyroidism, a potentially irreversible change to thyroid function, though the condition can be managed with medication, Schmid said.

Cancer doctors may soon have to weigh those drawbacks against Keytruda's benefits, should the FDA approve the drug. They'll also have other issues to consider, such as who treatment would help the most or which phase of the before-and-after surgery regimen is more beneficial.

But the data show "we have a new standard of care, going forward," Schmid said. "I personally struggle to see how one wouldn't discuss this treatment option with a patient."

https://www.biopharmadive.com/news/merck-keytruda-early-breast-cancer-esmo/603379/

Biogen’s Alzheimer Drug Gains Fade After Hospitals Balk

 Biogen Inc. shares sank to their lowest in more than a month after two major hospital systems and a group of health insurers said they wouldn’t administer its controversial Alzheimer’s disease medicine.

The biotechnology company’s stock fell as much as 7.1% to the lowest since June 7 after the Cleveland Clinic, Mount Sinai Health System in New York City, and some Blue Cross Blue Shield plans snubbed the use of Adulhelm. The U.S. Food and Drug Administration approved the drug on June 7, even after an advisory panel recommended against it.

If other medical institutions follow suit, it puts at risk the drug’s implied peak sales of $9 billion a year, said Salim Syed an analyst with Mizuho Securities USA. “The point hasn’t been fully digested by the Street on what it could mean,” he wrote in a note to clients.

The Cleveland Clinic won’t carry Aduhelm, known generically as aducanumab, on its formulary after a panel of experts reviewed trial results for the medicine. “Based on the current data regarding its safety and efficacy, we have decided not to carry aducanumab at this time,” the medical center said in an emailed statement, though it may reconsider as additional data becomes available.

Individual doctors may still prescribe the infusion, though patients won’t get it at the medical center’s clinics.

Mount Sinai also won’t be administering the $56,000-a-year drug until an ongoing government investigation is completed into whether any interactions between Biogen and FDA staff prior to the clearance were inconsistent with the agency’s policies and procedures. U.S. Lawmakers are also probing the approval.

“The FDA’s approval of Aduhelm has raised serious concerns and questions by clinicians, patients, and caregivers and a cautious approach is required,” according to a statement from the hospital network.

Mount Sinai and Cleveland Clinic’s plans to steer clear of Aduhelm were first reported by The New York Times on Wednesday and follow reports earlier this week that some Blue Cross and Blue Shield plans also won’t support Aduhelm use.

The nation’s largest health insurer, UnitedHealth Group Inc. is still working on its coverage policies, executives said in an earnings call on Thursday.

Investors have yet to hear how Medicare will cover Aduhelm amid concern it’s cost could bankrupt the system. Around 85% of people suffering from the brain-wasting disease are covered under the U.S. federal program by some estimates. Proposed coverage plans are expected early next year with a final decision thereafter.

Biogen has tumbled about 20% from its early June high. “Medical decisions should be based on science and data, so it is disappointing that patients living with Alzheimer’s Disease may reportedly not be able to access Aduhelm at some facilities,” the Cambridge, Massachusetts-based company said in a statement.

https://www.bloomberg.com/news/articles/2021-07-15/biogen-losing-alzheimer-drug-gains-after-providers-push-back

AI-driven ‘clock’ predicts aging-related illness and mortality

 Scientists in the US have developed an artificial intelligence-powered ‘clock’ that can estimate a person’s chance of developing an illness or dying based on the pattern of cytokines in their blood.

The “inflammatory age” or iAge clock – described in the journal Nature Aging – uses a snapshot of the level of chronic inflammation in the body to predict the chances of developing cardiovascular or neurodegenerative diseases and to give an estimate of lifespan.

The idea is that as the body ages levels of inflammation start to creep up, mainly as a result of chronic damage to cells and tissues. This systemic and chronic inflammation causes organ damage and promotes vulnerability to illness.

The researchers behind the project, led by Stanford University’s Nazish Sayed and Yingxiang Huang of the Buck Institute for Research on Aging, hope that identifying people with a high iAge early on could allow them to be treated for chronic inflammation, potentially extending healthy lifespans.

The research has grown out of the 1000 Immunomes Project (KIP) being run by Stanford University, which is attempting to establish biomarkers for healthy and sub-functional immune systems.

Using data from the KIP, the AI identified a set of 50 cytokines – immune signalling proteins – and developed an algorithm to give a single-number score that correlates with a person’s immunological response and the likelihood of developing aging-related diseases.

David Furman

“Every year, the calendar tells us we’re a year older,” according to KIP director David Furman, the study’s lead author. “But not all humans age biologically at the same rate. You see this in the clinic – some older people are extremely disease-prone, while others are the picture of health.”

The study backs up the hypothesis that this divergence traces in large part to the differing rates at which people’s immune systems decline, said Furman, but to date, there have been no metrics for accurately assessing an individual’s inflammatory status in a way that could predict clinical problems.

One cytokine in particular called CXCL9 seemed to have the closest relationship to the iAge score, and on further study seemed to be associated at higher levels with arterial stiffness – raising the risk of  strokes, heart attacks and kidney failure – as well as excessive thickness of the wall of the left ventricle of the heart.

The finding suggests that therapies that could reduce CXCL9 might be able to “reset” the iAge clock and dampen down the chronic inflammation that leads to accelerated aging.

“Our inflammatory aging clock’s ability to detect subclinical accelerated cardiovascular aging hints at its potential clinical impact,” Furman said. “All disorders are treated best when they’re treated early.”

https://pharmaphorum.com/news/ai-driven-clock-predicts-aging-related-illness-and-mortality/

Malaysia to stop using Sinovac COVID-19 vaccine after supply ends

 Malaysia's health ministry on Thursday (Jul 15) said the country will stop administering the COVID-19 vaccine produced by China's Sinovac once its supplies end, as it has a sufficient number of other vaccines for its programme.

Malaysia's inoculation drive will be largely anchored by the Pfizer-BioNTech mRNA vaccine moving forward, health minister Adham Baba told a news conference with other top ministry officials.

The Southeast Asian country has secured about 45 million doses of the Pfizer-BioNTech vaccine, enough to cover 70 per cent of the population, compared to 16 million doses of Sinovac's shot, the officials said.

"About half of the 16 million have already been distributed, so the rest will be used to cover second doses," Adham said.

"For those who have yet to be vaccinated, they will receive the Pfizer vaccine."

The government had previously said it had secured 12 million Sinovac doses, as part of a deal which would see state-linked firm Pharmaniaga carrying out a fill-and-finish process on the vaccine for local distribution.

The announcement to stop using Sinovac's inactivated virus vaccine comes amid increasing concern over its efficacy against new and more contagious variants of the coronavirus.

Neighbouring Thailand this week said it would use the AstraZeneca vaccine as a second dose for those who received the Sinovac shot, while Indonesia is considering a booster shot for those who received the two-dose Sinovac course.

Other vaccines approved in Malaysia include those of AstraZeneca, China's CanSino Biologic and the Janssen vaccine of Johnson & Johnson.

Malaysia also plans on Friday to announce its decision on whether to add the vaccine of China's Sinopharm, officials said.

With 880,782 cases and 6,613 deaths so far, Malaysia has one of Southeast Asia's highest per-capita infection rates, but also one of its highest inoculation rates, with about 26 per cent of its 32 million population receiving at least one dose of a COVID-19 vaccine. 

https://www.channelnewsasia.com/news/asia/malaysia-sinovac-covid-19-vaccine-stop-using-supply-ends-15227074