Russia-Ukraine war: Siemens, J&J vow to continue serving all patients; Conformis freezes Russian sales

 Russia’s invasion of Ukraine has sent shockwaves through global financial markets and business operations, compounded by sanctions that countries in the U.S., Europe and elsewhere have levied on the aggressor.

On top of governmental sanctions, many companies have announced individual decisions to halt operations within and sales to and from Russia, according to a report from Reuters. They span the world’s largest industries, from oil giant ExxonMobil to global bank HSBC to tech monolith Apple. Now, some medtech companies are following suit.

Wednesday, customized orthopedic implant maker Conformis said it would freeze all distribution to Russia and other entities based in the country and would stop pursuing new business opportunities in the region. The decision to step back came shortly after Massachusetts-based Conformis launched a new distribution agreement in Russia, CEO Mark Augusti said in a statement.

“While we were looking forward to working with our agents and surgeons in Russia, we believe it is important that our business aligns with our values,” Augusti said. “We will monitor this closely and look to resume development when appropriate.”

“We feel empathy for the Russian people and potential patients of Conformis, who may have benefited from our products," he said. "However, given the unnecessary and unprovoked military invasion of Ukraine instigated by the Russian leadership, we can no longer in good conscience, sell our products or services in the Russian market.”

Augusti went on to urge the company’s fellow international businesses to follow suit and sent “thoughts and prayers” to Ukraine, singling out any relatives of Conformis employees residing there.

Elsewhere, in a statement sent to Fierce Medtech, Siemens Healthineers said that while it would comply with all export control requirements and sanctions, it would also continue to support healthcare providers and patients in Russia, citing the right to medical care embedded in the Universal Declaration of Human Rights. It also noted that it expects “an indirect negative impact on our business” due to financial sanctions, which don’t directly target the healthcare industry.

“As a medical technology company, our priority remains to support medical professionals and patients in every circumstance and in every country. We believe that sanctions should not have adverse humanitarian consequences for the civilian population and hope we will be able to continue to support those who need us in both Ukraine and Russia,” the company said.

“Siemens Healthineers strongly condemns the invasion by Russian forces of Ukraine, a sovereign European nation, in clear violation of international law. We are moved by the courage of the Ukrainian people.”

Johnson & Johnson took a similar approach. In a statement sent to Fierce Medtech, it said, "Our priority is the safety of our employees and their families who are affected, and we are supporting them in every way we can. We are also committed to ensuring that our essential medical products will reach the people who need them within the region. We are monitoring the changing situation as well as the degree of impact on our business."

According to a report from the U.S. commerce department’s International Trade Administration, the market for medical equipment in Russia totals more than $5 billion.

As of 2018, nearly 20% of that market was dedicated to diagnostic imaging, while consumables took up 15% and patient aids clocked in at 14%. Dental products and the orthopedics and prosthetics segment each made up about 9% of the market, and the remaining third of the market came from “other medical devices.”

The report notes that many of the world’s largest medical device makers have a presence in Russia, including Johnson & Johnson, GE Healthcare, Medtronic, Baxter, Stryker, Philips and Siemens Healthineers plus its now-subsidiary Varian Medical Systems.

https://www.fiercebiotech.com/medtech/russia-ukraine-war-conformis-freezes-russian-sales-while-siemens-vows-continue-serving-all

Pfizer seeks silver lining in failed C. diff vaccine trial

 Pfizer’s vaccine for Clostridium difficile (C. diff) looks like it may join a growing list of candidates that have been shelved or delayed, after the shot failed to meet its primary objective in a phase 3 trial.

The pharma company was quick to point out however that the CLOVER trial of PF-06425090 was undermined by a lower-than expected rate of C. diff infection (CDI) as a result of social isolation caused by the COVID-19 pandemic, and to highlight secondary endpoints in the trial that it said point to a “strong potential effect” for the shot.

First, the bad news. The vaccine wasn’t able to show a significant reduction in the first primary episode of CDI 14 days or more after the second and third doses of the shot compared to placebo in the 17,500-patient trial, which enrolled subjects 50 years of age and older who were at high risk of infection.

Top-line efficacy for the vaccine was 49% at 12 months, 47% at 24 months and 31% at final analysis, said the drugmaker, which was forced to carry out the assessment after 42 cases of CDI, fewer than the 66 cases laid out in the trial protocol.

That was a disappointing result, but Pfizer has latched onto encouraging findings on secondary measures of efficacy including  reducing the severity of CDI, and what it said was 100% efficacy in preventing medically attended CDI, with zero cases among patients taking the vaccine versus 11 in the placebo group.

The company came out with the usual mantra of evaluating the data and conferring with regulators before deciding on the future of the programme, and said it would present the data in full at an future medical congress.

The jury is out on whether the FDA might consider approving the vaccine on that secondary performance, but there’s no doubt of the big unmet medical need. With no approved vaccines to date, C. diff causes nearly 30,000 deaths each year in the US, and recurrent infections with the bacterium make up 10%-15% of all hospital-treated infections.

As it stands, PF-06425090 is still leading the field among candidate vaccines for C. diff since Sanofi ended development of its candidate in 2017, ahead of Valneva whose VLA84 has been shelved after phase 2 while it looks for a development partner.

The only other company with a C. diff vaccine candidate in clinical development is GlaxoSmithKline, whose GSK2904545A is in phase 1.

PF-06425090 has been held up as one of the top prospects in Pfizer’s pipeline, with blockbuster sales potential.

It’s also viewed as an important future driver of growth for the company once its windfall revenues from COVID-19 therapies start to wane, although Pfizer has been using that new financial power to make a flurry of pipeline-bosting deals, including a $6.7 billion play for Arena Pharma.

https://pharmaphorum.com/news/pfizers-seeks-silver-lining-in-failed-c-diff-vaccine-trial/

Gene Therapy Trials for Sickle Cell Disease Hold Hope for Durable Effects

 Sickle cell disease is nearing a cure. Recent gene therapy research has created what appears to be a durable response in terms of producing normally-shaped red blood cells and completely reducing the pain associated with the disease.

The study, Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease, published in the New England of Medicine (NEJM) and funded by bluebird bio, outlines a successful approach that adds a gene to the stem cells that eventually become blood-producing cells.

“Gene therapy with autologous stem cells extends the possibility of a cure to all patients without the need for immunosuppression,” Martin Steinberg, M.D., professor of medicine at Boston University School of Medicine, wrote in a subsequent editorial in the NEJM.

The study’s first author, Julie Kanter, M.D., director of the UAB Adult Sickle Cell Clinic at the University of Alabama at Birmingham, and a team of researchers from throughout the U.S. conducted a Phase I/II trial. The 35 patients received one infusion of LentiGlobin and were followed a median of 17.3 months. Some were followed for up to 37.6 months, which is thought to be the longest follow-up period of any sickle cell study.

The researchers found that hemolysis markers decreased and, importantly, that total hemoglobin increased. Most of the red cells (85% in the optimized group of patients) exhibited an increase in HbAT87Q, an anti-sickling hemoglobin that is 99.9% similar to healthy adult hemoglobin. The difference is an amino-acid substitution to sterically inhibit polymerization of sickle hemoglobin.

Of the 25 patients who were able to be evaluated for vaso-occlusive events (which causes pain, stroke, leg ulcers, renal insufficiency and spontaneous abortion), three had moderate vaso-occlusive events after the infusion. Severe events dropped to zero. To put this in context, a two-year baseline showed that all 25 patients had experienced both moderate and severe vaso-occlusive events before the infusion, so this was a notable reduction.

In terms of safety, although “one-third of the patients had serious adverse events after infusion,” Kanter and colleagues wrote, in all but three patients those events were considered to be unrelated to the infusion. They included abdominal pain, drug withdrawal syndrome, nausea and vomiting.

To develop the LentiGlobin therapy, blood-forming stem cells are collected from the patient’s blood. Then, lentiviruses deliver a modified copy of the beta-globin gene into the stem cells, which are later reinfused into the patients. There is no risk of rejection because the therapy uses a patient’s own cells. The modified stem cells accrue in the bone marrow, where they begin making healthy new red blood cells.

Before treatment, however, the patients must be conditioned. This involves a high dose of chemotherapy to kill existing stem cells to make room for the modified stem cells. There is a small risk that the chemotherapy can induce cancer and, in fact, two of the initial group of patients to be treated developed leukemia several years after therapy. No cancers were reported in the group receiving the later, optimized treatment, however.

In sickle cell disease, the red blood cells are shaped like the sickles that once were used to cut wheat. Twenty-first-century Americans are more likely to associate the shape with the crescent moon. These sickle-shaped cells are rigid and fragile, which shortens the lifespan of the red blood cells and results in anemia and vaso-occlusive episodes that may lead to organ damage.

Sickle cell disease is caused by mutations in the HBB gene, and is inherited. This disease affects approximately 100,000 Americans and is most common in the Black community, although Hispanics also are at risk. To put figures to the disease, 1 in 13 Black newborns carry the sickle cell trait and 1 in 365 are born with the disease. In Hispanics, the figure is 1 in 16,300.

While LentiGlobin therapy appears promising, gene therapy remains very expensive, and, as Steinberg pointed out, “Most patients with this disease live in Africa and India, where access to highly technological health care is limited. What is needed are more drugs that can be taken orally and increase fetal hemoglobin levels.”

Nonetheless, “You cannot overstate the potential impact of this new therapy,” Markus Y. Mapara, M.D., Ph.D., professor of medicine at Columbia University Vagelos College of Physicians and Surgeons and a co-author of the study, said in a statement.

The next stage of the research involves developing less toxic approaches to conditioning the bone marrow before gene therapy. “The eventual goal will be to give this treatment as early as possible, well before patients develop organ damage and other complications of sickle cell disease,” Mapara said.

https://www.biospace.com/article/gene-therapy-trials-for-sickle-cell-disease-hold-hope-for-durable-effects-/

WHO recommends Merck's COVID pill for high-risk patients

 A World Health Organization (WHO) panel on Wednesday backed the use of Merck & Co Inc's COVID-19 antiviral pill for high-risk patients.

The expert panel conditionally recommended the pill, molnupiravir, for patients with non-severe disease who are at high risk of hospitalisation, such as the immunocompromised, the unvaccinated, older people and those with chronic diseases.

The recommendation was based on new data from six clinical trials involving 4,796 patients.

Since molnupiravir's U.S. authorization in December, demand for the pill among COVID-19 patients has taken a hit from comparatively low efficacy and potential safety issues for certain groups.

The WHO panel said it was also preparing recommendations for Pfizer Inc's rival COVID-19 antiviral pill, Paxlovid.

Pfizer's pill was shown to be nearly 90% effective in preventing COVID-19 hospitalizations and deaths, compared with 30% for molnupiravir.

The recommendations from the WHO's Guideline Development Group (GDG) are aimed at helping doctors provide the best care for patients in fast-moving situations such as the COVID-19 pandemic.

The panel said that young and healthy patients, including children, and pregnant or breastfeeding women should not be given molnupiravir due to potential risks such as defects in a developing fetus, as shown in animal studies.

The WHO guidelines, published https://www.bmj.com/content/370/bmj.m3379 in the British Medical Journal, said no recommendation on molnupiravir's use has been made for patients with severe or critical illness as there was no trial data for the group.

The panel also updated its guidance for the use of Regeneron Pharmaceuticals Inc's COVID-19 antibody cocktail. It now recommends the drug only for people who are not infected with Omicron as new preclinical data has shown it is not effective against the variant.

In January, the panel recommended the use of Eli Lilly's baricitinib for patients with severe COVID-19 in combination with corticosteroids, and conditionally endorsed GlaxoSmithKline and Vir Biotechnology's antibody therapy for non-severe patients at the highest risk of hospitalisation.

https://www.marketscreener.com/quote/stock/REGENERON-PHARMACEUTICALS-10649/news/WHO-recommends-Merck-s-COVID-pill-for-high-risk-patients-39645276/

Drugmakers, device companies say sanctions may hinder medical supplies to Russia

 

Western drugmakers and medical device companies warn their plans to keep selling products to Russia may be complicated by economic sanctions targeting the country and its major banks in punishment over Moscow's invasion of Ukraine.

Sanctions levied by the United States, Britain, Europe and Canada against Russia do not apply to medicine and medical equipment, and the industry has a responsibility under international humanitarian law to continue supplying these products, industry trade groups, policy experts and company officials said. International aid groups are pushing to keep critical medicines flowing into Ukraine, where Russian troops are seeking to wrest control of major cities, prompting more than 870,000 Ukrainians to flee their country and millions to seek shelter from air strikes. Already, pharmacies are reporting shortages of medical supplies.. Many Western companies said they will stop selling everything from cars to movies in Russia. Transactions related to medicine and medical devices, as well as food, have been authorized despite U.S. and EU sanctions.

But sanctions that have cut off Russian banks from the international financial system, as well as decisions by major shipping companies to suspend service to the country, could hinder the delivery of medical supplies as well.

The removal of seven Russian banks from the SWIFT international payment system - as well as the ongoing assault on Ukraine - could cause interruptions, MedTechEurope, the European lobby group for medical device companies, said. Without access to that payment system, it becomes more difficult to transact with Russia. "The freezing of bank transfers could indeed have an impact on the export of medical devices from the EU to Russia, and we are actively looking into the extent of this and will see how the situation evolves," the MedTechEurope spokesperson said.

The European Federation of Pharmaceutical Industries and Associations in a statement called for safe passage of medicines and vaccines to people in need in Ukraine, neighboring EU member states and Russia.

The U.S. drug industry group PhRMA said it supports the continued exemption from all sanctions of medicines and the materials needed to manufacture them.

Under international humanitarian law, everyone has a right to access essential medical services and supplies, including drugs and vaccines, Lawrence Gostin, a public health law expert at Georgetown University said. "During times of conflict, this right of uninterrupted access to essential medical supplies has often been violated," Gostin said. "Governments that impose sanctions are also supposed to make an exception for medical supplies. Yet sanctions often disrupt medical services and supply chains."

The United States in a general license issued last week authorized transactions related to the export or re-exportation of medicine and medical devices with Russia. It has also issued carve outs for energy-related payments and international organizations, among others.

The U.S. Treasury Department declined to comment on the issue.

The EU supplied Russia with 6.5 billion euros ($7.23 billion) of pharmaceutical products in 2020, about 8.4% of the region's total exports to Russia, according to Eurostat data. It sent about 1.6 billion euros of medical equipment to the country in the 12 months ended September 2021, according to MedTech Europe.

U.S. government data shows that in 2021, pharmaceuticals and medical equipment represented about 8% of all U.S. goods exported to Russia. It sent $355 million worth of medicines and $157 million worth of medical equipment to the country.

Graphic, U.S. medical exports to Russia:

Top shipping group A.P. Moller-Maersk on Wednesday warned that shipments to Russia, including medical supplies, risk being damaged or spoiled due to significant delays at ports and customs.

Drugmakers including Switzerland's Novartis, Denmark's Novo Nordisk and Lundbeck, Britain's GlaxoSmithKline and U.S.-based Eli Lilly said they are working to ensure patients have continued access to their medicines.

Novo Nordisk, the world's largest maker of diabetes medicines, said it would do "all we can to maintain supply in Ukraine and Russia" but it anticipates sanctions will make that more difficult. It has already had issues delivering medicine to Ukraine.

"The supply of medicines may be indirectly affected by sanctions in other areas, and we will do whatever we can to ensure the citizens of Russia receive their life-saving medication," Novo Nordisk said in an emailed statement.

Lundbeck, which specializes in treatments for depression, said it will continue to serve patients who need medicine in Russia.

"As long as we can supply medicine to patients in Russia within the current sanctions, we will do so," chief commercial officer Jacob Tolstrup said in a written comment.

https://www.marketscreener.com/quote/stock/GLAXOSMITHKLINE-PLC-9590199/news/Drugmakers-device-companies-say-sanctions-may-hinder-medical-supplies-to-Russia-39646667/

Hong Kong transport operators, supermarket cut services as COVID surges

 

Hong Kong's subway operator, bus and ferry companies, and one of its biggest supermarket chains, are cutting back services due to a worsening COVID-19 outbreak that has seen daily infections explode since early February.

The surge in cases and mixed messaging from government officials have triggered an exodus of people from the global financial hub, where authorities are clinging to a "dynamic zero" coronavirus strategy that seeks to stamp out all outbreaks.

Many restaurants and shops in the Chinese-ruled city have closed while its main financial district is eerily quiet and few people are out and about in normally bustling neighbourhoods.

Hong Kong's Transport Department said 98 bus routes would be suspended with operators facing critical manpower shortages.

A rise of infected people coupled with a drop in customers due to stringent social distancing measures made it hard to maintain operations, it said in a statement late on Wednesday.

The city's subway operator, MTR Corp, said on Thursday it would cut services on eight lines because of staff shortages and a sharp drop in customers.

"We have been striving to maintain train service despite the worsening COVID-19 situation. However, the latest development of the pandemic is affecting the manpower for daily operations," it said on its website.

Two ferry operators that ply the city's harbour between the main island of Hong Kong and the Kowloon peninsula said they would suspend services until further notice.

ParknShop, one of the city's largest supermarket chains, said it was shortening its operating hours for more than 200 outlets to protect its staff and customers. Some outlets would close as early as 3 p.m., it said.

Since the coronavirus emerged in the Chinese city of Wuhan in late 2019, the tally of infections in the former British colony stands at more than 290,000, with a death toll of about 1,100.

About 700 of those deaths have been in the past week, with the majority unvaccinated people.

Health experts from the University of Hong Kong estimated about 1.7 million people had been infected as of Monday, with the coming week expected to bring a peak of about 183,000 daily infections.

'VERY DAMAGED'

There has been widespread confusion this week because of mixed messages from authorities over whether a city-wide lockdown would be imposed and the almost daily tweaking of coronavirus rules.

Highlighting growing public frustration, prominent businessman and government adviser Allan Zeman said Hong Kong's international reputation had been "very damaged" and alarm had been created by the confusing messages.

Supermarket and pharmacy shelves have been emptied daily by anxious residents stocking up despite assurances from the government that whatever type of lockdown is imposed, people would be able to buy necessities.

City leader Carrie Lam has said the government had no plan for a "complete lockdown" while it conducts compulsory testing of the city's 7.4 million residents. The government would announce details of the plan when finalised, she said.

Hong Kong has implemented its most draconian rules since the pandemic began with international travel restricted, most venues shut and a ban on public gatherings of more than two people. Many members of the public fear being forced to isolate and separated from their families if they test positive, prompting an exodus, particularly of expatriates.

Some Western diplomats said the government had been "refusing to engage" in recent weeks on coronavirus strategy and compulsory testing, not replying to requests for clarification on policy as the outbreak worsens. This was making it difficult for them to advise their citizens what to do, they said.

Restrictions mean very few international flights can operate through Hong Kong but nevertheless more than 70,000 people left the city in February, the most since the start of the pandemic, according to government data.

About 300 Swiss nationals are planning to leave on a charter flight next week due, media reported. A spokesman for the Swiss consulate said it was aware of the flight but could not provide details.

https://www.marketscreener.com/quote/stock/WYNN-MACAU-LIMITED-5774272/news/Hong-Kong-transport-operators-supermarket-cut-services-as-COVID-surges-39645896/

Merck KGaA Earnings and Sales Climbed in 2021, Driven by Life Science

 German pharmaceuticals-and-chemicals company Merck KGaA on Thursday posted higher 2021 earnings and sales, driven by its life science division, and proposed a higher dividend.

The company--which had raised its guidance three times over the course of 2021--posted after-tax profit of 3.07 billion euros ($3.41 billion) for the year, up from EUR1.99 billion the year prior.

Ebitda pre--a closely-watched company metric which measures earnings before interest, taxes, depreciation and amortization before one-time items--was EUR6.10 billion in the year, up from EUR5.20 billion the year before, Merck said.

Net sales came in at EUR19.69 billion compared with EUR17.53 billion the year prior, the company said.

Looking ahead, Merck expects strong organic growth in net sales and Ebitda pre in 2022, driven by all business sectors but particularly by its life science division.

The company proposed a dividend raise of EUR0.45 to EUR1.85, which it said was an all-time high.

https://www.marketscreener.com/quote/stock/MERCK-KGAA-436395/news/Merck-KGaA-Earnings-and-Sales-Climbed-in-2021-Driven-by-Life-Science-Raises-Dividend-39646830/