The low worldwide prices for antibiotics, combined with the need to carefully ration sale of any powerful new drugs that come to market to preserve their efficacy, continue to dampen industry investment in desperately-needed treatments for new drug-resistant superbugs, according to a sweeping new report by the AMR Industry Alliance, released today.

While civil society advocates have focused significant attention on the high prices of some new drug treatments for non-communicable diseases such as cancer, the AMR Industry Alliance Progress Report, sheds light on market forces playing out at the other end of the spectrum.

In this case, low market prices are thwarting efforts to bring promising new treatments to market, treatments needed to combat so-called “superbugs” – bacteria, viruses and parasites that are increasingly resistant to existing drug treatments.

The findings about investment trends and barriers should be a “wake-up call” for people concerned about rising antimicrobial resistance (AMR) in disease-causing pathogens, said Thomas Cueni, head of the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) and Alliance Chair in a press release.

He added, “Discovering new and effective ways to leverage positive preclinical pipeline results and working together to ensure that late-stage antimicrobial drug discovery and development is better supported are vital.”

Pharmaceutical technician in sterile environment working on production of pills at pharmacy factory

The same market forces that are preventing new treatments from reaching the marketplace are also leading to increased shortages in some of the most common antibiotics, which billions around the world take for granted – although an estimated 5.7 million people die every year due to lack of access, the report states.

The massive new report, which tracks successes as well as setbacks in the global fight against superbugs across the range of AMR issues, is the synthesis of a detailed survey among 65 member companies of the AMR Industry Alliance, a group of life science companies dedicated to curbing the growing threat of superbugs.

According to the report, some $US 1.6 billion was invested by the private sector in 2018 in the development of new treatments that could help combat antimicrobial resistance, along with some $US 500 million in public funds. But that probably represents a flat trend, or even a decline over private sector investments in previous years, said industry experts interviewed by Health Policy Watch.

Investors are still funding pre-clinical discoveries of potential antibiotics, as well as new generation diagnostic tests, where there is a healthy pipeline. But little money is going towards funding costlier late stage R&D, such as clinical trials, the report finds.

Smaller biotech companies are especially struggling to secure investments that “will allow them to survive,” says Greg Frank, director of Infectious Disease Policy at the Biotechnology Innovation Organization, a member of the AMR Industry Alliance told Health Policy Watch, in an interview.

He described the chill cast over the industry after the biotech firm Achaogen went bankrupt, shortly after it brought a new antibiotic to market approval. This was followed by the filing of bankruptcy by Melinta, another biotech firm with a drug candidate in late stage development.

“While Melinta continues to operate during its restructuring, this doesn’t send a good signal to the investment community. It says, ‘this is an area that you should never touch’,” said Frank.

Frank explained that once new antibiotics are approved and brought to market, they are usually regulated to only treating the most drug-resistant diseases. While that may prevent resistance to the new drug from developing as quickly, this results in only small amounts of sales. Antibiotics are also expected to be priced lower than new drugs for other diseases such as cancer, so it is difficult for smaller companies to recoup the costs of R&D and manufacturing in the first few years after new antibiotic is approved.

Thus, Frank adds, many smaller firms will bring a product to mid-development, then “shop around” and sell their product to larger firms that have the capital to take on the risk of bringing a new antimicrobial to market.

However, with the exit of several large research-based biopharmaceutical companies such as Novartis, Sanofi, and AstraZeneca from the AMR drug development space in the past two years, smaller companies are no longer able to follow this model to secure investments.

That means that highly promising early-stage discoveries may never reach patients unless investment in later and more costly sages of R&D for these products is ramped up, and new government incentives for antibiotic research are enacted.

Further Downward Trend Predicted – Unless Public Sector Rewards Increase

The industry report predicts that investment in AMR R&D may see a downwards trend in the coming years unless governments enact new incentives to pull large pharmaceutical companies back into the space. Frank says that ultimately, small companies with potential novel compounds that could “treat a public health need” must also be able to incentivize investors and make a sustainable return on investments.

One potential solution, said Frank, is the creation of new types of “market-entry rewards” by the public sector that reward a company with an approved antibiotic that meets a specific criteria with some form of cash benefits or its equivalent.

On example of such a reward would be a more flexible formula for “exclusivity vouchers,” which extend the patented life of a product by a year and have been created in some countries to reward new drug innovations. If these were made transferable, they could be used by a company to protect another, more profitable product in its portfolio or sold – providing added return on investment.

Currently, these vouchers can only be applied to the approved antibiotic, said Frank, but for a medicine that is not very profitable, this creates little incentive to advance research and production:  “I once had a company tell me, ‘it’s great that we have it; now it gives me another 5 years to solely lose money on my medicine.’”

Diagnostics – Bright Spot on AMR Investment Horizon

The threat of drug-resistant superbugs has often focused on the “arms-race” between the development of stronger disease-causing pathogens and new drugs to fight them.

Lab researcher dripping test liquid in petri dish and checking reaction.

But the AMR report also highlights one brighter spot – the increased investment in new diagnostics development, which can play a critical role in reducing drug resistance.

Expanded use of diagnostics can help make sure that the “right tools” are available for the “right patient” at the “right time,” explains Jean-Louis Tissier, vice president of public and government affairs-AMR at the in-vitro diagnostics company bioMérieux, an AMR Industry Alliance member.

For example, it can be difficult to tell if certain diseases are caused by bacteria or viruses based on symptoms alone. Acute respiratory infections, which often present with cold-like symptoms, can be caused by both bacteria or viruses. But prescribing antibiotics for viral illnesses contributes to growing drug resistance without actually treating the patient effectively.

For instance, a simple lab test for the bacterial biomarker pro-calcitonin that takes less than one hour, can tell a physician if the patient has a bacterial infection; it can also help the physician decide for how long the patient might need antibiotic treatment. This test is being widely used in some European countries, such as Germany, he said.

“Today, you see an increase in [drug resistance] because in some countries there is overuse of antibiotics… if you go to the south of Europe or the US you can see an increase in resistance in patients who are over-prescribed with antibiotics,” says Tissier.

With new diagnostic tools becoming available, the next step is to support low- and  middle-income countries to invest further in diagnostic and laboratory capabilities that can use these tools effectively, said Tissier. “Health care facilities are looking at the most efficient systems, and these countries are where we need to demonstrate the economic and medical value of diagnostics solutions. Yes, there is a cost at the laboratory level [to do a diagnostic test], but at the hospital level diagnostics are a key source of savings.”

Going a step further, newer molecular biology diagnostics for conditions such as acute respiratory infections can provide clinicians with even more accurate information about the type of pathogen involved, as well as to which drugs it may respond, leading to faster, more appropriate treatments for patients.

 Addressing Antibiotic Shortages

The same market forces that are preventing new treatments from reaching the marketplace also are also leading to supply-chain shortages for some of the most common and critical antibiotics, which billions around the world take for granted, while millions of other people still lack access, the report finds.

“Continuity of supply of antibiotics is of paramount important and there are many elements needed to ensure this is the case, including supply chains with suppliers that have robust quality and environmental health and safety systems in place,” says Steve Brooks, chair of the manufacturing working group at the AMR Industry Alliance.

“Maintaining robust systems takes management commitment and money, and it’s these costs that may not be fully valued in the current procurement practices when antibiotics are purchased by large/institutional buyers.”

Shortages also are linked to low prices, which have prompted the withdrawal of many manufacturers from antibiotic production, leading to increased concentration in supply chains that can also create bottlenecks when just one manufacturer shuts down or fails to fill an order.

Solutions can involve what some have called the “Netflix” model of longer-term contracts between health systems and drug manufacturers, said Frank. This allows drug suppliers to rationally plan production and therefore supply, without fear of the sudden loss of a customer.

Environmental Concerns, and Other Challenges

On the enviromental front, where the release of antibiotic residues from pharma production facilities can foster development of drug resistant bacteria in sewage effluent, industry members are taking additional steps to control the release of such residues into the environment, the Alliance report says. Members are two years ahead of schedule in establishing a standard framework for limiting manufacturing emissions to “no-effect” concentrations within the next seven years.

“Alliance manufacturers are committed… to auditing their sites and those of their suppliers against the Alliance Common Antibiotic Manufacturing Framework and assessing concentrations of antibiotic residue in waste streams,” explained Brooks.

The framework dictates that for a factory supplying one million antibiotic tablets per year, the concentration of antibiotic in the collected waste water must be less than 1 microgram per litre. Effectively this would mean that residue concentrations released annually into wastewater effluent would not contain enough active ingredient for even one antibiotic tablet, he said.

So far, the findings show that 82% of participating companies’ antibiotics manufacturing facilities meet or partially meet the framework requirements. Those suppliers that don’t meet the standard are required to take action to reduce their antibiotic emissions, or potentially face losing their contracts.

“In the event changes are not not being made in a timely manner, members may look at alternate supply arrangements,” said Brooks.

Industry members have also made efforts to combat falsified and substandard antimicrobials; develop strategies to improve access to medicines in low-income countries; and formalize standards for appropriate use of antibiotics.

Together, the AMR Industry Alliance group of some 91 biotech, diagnostics, generic medicines, and research-based biopharma companies account for approximately one-third of the global antibiotic supply, and nearly half of the antibiotics in pre-clinical development, and half of the diagnostics sector producing AMR-related products.

Additional information about the report can be found at the AMR Industry Alliance.

Image Credits: AMR Industry Alliance.

The mysterious new pneumonia coronavirus that has emerged in Wuhan, China may also be transmitted between people, health experts in China and Geneva now suspect. Officials are concerned that the outbreak may also spread globally as a new exported cases of the novel virus were confirmed in Thailand on Friday and Japan on Thursday, and local sources reported a second death due to the virus in China.

The outbreak has claimed its second victim, a 69-year old man named ‘Mr. Xiong’ who was reportedly hospitalized on 31 December 2019. The Wuhan Municipal Health Commission said in an official statement that the man’s condition deteriorated on 4 January and died on 15 January at Wuhan JinYinTan Hospital shortly after midnight (translated from Chinese).

The second Thailand case was also in a Chinese national who was found to have fever on arrival at Suvarnabhumi airport on 13th January. Initially hospitalized for mild pneumonia, Thai and WHO officials have since confirmed the man to be positive for the new viral disease.

Earlier in the week, reports surfaced that the coronavirus, dubbed 2019-nCOV, has been confirmed in family clusters, including at least one family member who had not visited the Wuhan seafood and live animal market that is suspected of being the source of the new infectious agent.

On Thursday Japan’s Health Ministry also reported its first case of the virus in a man who fell ill during a visit to Wuhan earlier in the month, although he had not visited the market, said NHK World News. The man was hospitalized upon his return to Japan on 6 January, and was discharged on Wednesday. Later Thursday, WHO confirmed the report of the Japanese case.

Seafood and fresh food market in Wuhan, Hubei, China. Most confirmed cases of 2019-nCoV were traced back to Huanan Wholesale Seafood Market, although at least two confirmed cases have reported never visiting the market. Authorities are concerned that this could mean the source of infection is present in other markets, or the disease could spread directly from person to person.

Chinese authorities and researchers are now struggling to pinpoint the original infection reservoir among the live animal species sold in the market; routes of transmission; and confirm definitively if the disease can be spread by person-to-person contact – possibly in a weakened form.

A commission of technical experts from Hong Kong, Macao, and Taiwan visited Wuhan on 13 – 14 January and found two family clusters of confirmed cases – three male family members living together and a husband-wife duo.

The three men were all believed to have contracted the disease from working at the seafood market, Dr Chuang Shuk-kwan, a commission expert from Hong Kong, was quoted saying at a press conference Wednesday morning in the South China Morning Post. However, the wife with a confirmed case of the 2019-nCoV infection had not recently visited the market where her husband worked as a trader, according to a statement by Wuhan authorities (translated from the Chinese). Chuang Shuk-kwan said this could suggest “limited” human-to-human transmission of the virus is occurring.

In Geneva, a WHO official expressed similar concerns: “From the information that we have, it is possible that there is limited human-to-human transmission, especially among families who have close contact with one another,” Maria Van Kerkhove, acting head of WHO’s Emerging Diseases Unit, told journalists at a briefing.

The possibility that the virus is being transmitted between humans – but resulting in asymptomatic or mild cases that remain undetected by the health system – is an important concern for Chinese authorities as hundreds of thousands of people prepare to travel around the country during the Lunar New Year, the annual holiday that begins January 25.

The number of confirmed cases has risen by 44, and caused two deaths. Three cases have now been reported outside of China, in Thailand as well as Japan. Officials are investigating whether the latest Thai case has had contact with the local seafood market where most cases have been traced. The Japanese case, announced publicly Thursday, was a man who fell ill on 3 January and had been in close contact with some of the Wuhan residents who became infected, although he did not visit the suspect live market. He was hospitalized after returning home to Japan and has since recovered. In Thailand, a case was reported on 8 January in a 61- year old Chinese tourist from Wuhan who became sick while traveling to Bangkok for a vacation; she was immediately hospitalized and is also now recovering, according to WHO.

While that patient reported visiting a local fresh market in Wuhan on a regular basis, she had not visited the Huanan Seafood Wholesale Market, where most of the other cases have been traced. Experts say that this means that the source of the infection could be a live animal commonly sold at other markets as well.

Number of New Ebola Cases Stabilizes

Infectious disease outbreaks, epidemics, as well as increasing drug-resistance among certain viruses and bacteria, are among a list of urgent global health challenges for the next decade, WHO said this week.

And along with the emerging coronavirus in China, the new year of 2020 also opened with the world still battling a stubborn, 1.5 year-long Ebola outbreak in the Democratic Republic of the Congo.

The last embers of the Ebola outbreak in the Democratic Republic of the Congo are still smoldering as the response effort moves into the new decade. The deadly virus resurged in December, after a month of civil unrest and armed attacks on health workers in eastern DRC – the epicenter of the outbreak. Although there were signs that numbers may be stabilizing in the new year. Some 14 new cases were confirmed between 8-14 January, compared to 12 new cases the previous week. Case numbers are down again after a small resurgence of 27 cases in the first week of December 2019.

A Red Cross team demonstrates a safe and dignified burial.

Insecurity and community mistrust have plagued the response, with the International Federation of the Red Cross confirming Wednesday that yet another attack on Ebola responders had occurred at a safe burial conducted in Mambasa. Two Red Cross volunteers were injured.

“Despite an overall improvement in the community’s acceptance, this attack shows that community engagement is crucial to building trust and ending the Ebola outbreak,” IFRC Africa tweeted on Wednesday. On Thursday, WHO reported that several health areas continue to be difficult to reach due to insecurity, including Mandima Health Zone, where there are rumors of several community deaths in Lwemba Health Area.

In 2019, WHO recorded 978 attacks on health care workers and outbreak responders, resulting in 193 deaths. As of 14 January, 3406 Ebola cases have been reported, of which 2236 cases have died.

Story updated 17 January 2020

Image Credits: Arend Kuester/Flickr, IFRC.

More public disclosure and information-sharing about drug prices and their R&D costs, is key to determining a fair price for essential medicines, concludes a series of five articles on fair pricing published Monday in the BMJ. The series, supported in part by the World Health Organization, highlights the increased priority drug price transparency is receiving on WHO’s agenda.

The five articles discuss the barriers to information-sharing between private and public sectors about R&D costs, as well as between health systems in different countries, which typically keep data on real drug purchase prices confidential, which have become a central theme on the transparency agenda over the past year.

But the series also explores some new, win-win approaches to pricing that could help make higher-price medicines more affordable while maintaining incentives for the private sector to invest in R&D and manufacturing, according to the study authors.

“Transparency is a key element to determine what is fair, but there is an absence of reliable data on development costs,” Alison Colbert, technical officer in the Essential Medicines and Health Products Department at WHO wrote in an introductory editorial published in the BMJ for the series. The editorial was co-authored by top WHO officials, including the director and assistant-director of the Essential Medicines and Health Products Department at WHO, Suzanne Hill and Mariângela Simão, along with Soumya Swaminathan, chief scientist at the WHO.

The WHO officials add that “ultimately, there is no simple algorithm that will calculate a fair price for each medicine,” but that transparency and collaboration will ensure that the “right data” are available to the “right stakeholders” to help ensure affordable access to essential medicines.

However, before “fair” prices can be set, the global health community must first agree about what a “fair” price means.

“”For too long, governments and other purchasers of medicines have not had clear frameworks for how to assess the fairness of medicines prices, especially when considering pricing within a global market. We know medicines prices have been climbing year after year, but how can we assess when a high price is too high?” asked Suerie Moon, co-director of the Global Health Centre at the Graduate Institute.

Suerie Moon et al. propose hypothetical price ceilings (ie, the maximum that is affordable to the buyer) and fair prices for countries with different affordability thresholds. Prices below the red line indicate hypothetically “fair” prices.

In the first article in the series, Moon and her colleagues from WHO highlight the differences between what matters to sellers’ and buyers’ in defining a “fair price.” The authors note that both groups have a very different set of parameters.  Buyers may consider a drugs overall value to individuals and health systems;  affordability and financial hardship risks; and supply security. Pharmaceutical companies, on the other hand, are concerned with prices that cover the costs of R&D, regulation, manufacturing, and distribution while generating a profit.

Moon and her colleagues propose a framework that combines both buyers’ and sellers’ concerns in defining a range of fair prices for medications, proposing that price ceilings for medicines could be set by consideration of consumers’ concerns while price floors could be set by manufacturers’ priorities. Public intervention should occur in cases where prices fall outside of this range.

“A key concept here is that companies can earn a fair profit, but the profit should not be excessive and should not come at the cost of affordability to patients,” Moon clarified.

Altogether, the series includes five papers that address issues around medicines prices that could be described as “fair” while still incentivizing the pharma industry to invest, entitled as follows:

While generally, high prices are associated with patented medicines, the second and third papers also explore lesser-publicized issues of high pricing for biosimilars, generic medications, as well as the prices of  off-patent drugs which may have too few manufacturers. The fourth paper argues for a radical shift towards alternate business models that reward the pharma industry for innovation, but not through the vehicle of prices, to spur more development in areas of unmet health need.

Finally, the last paper presents how the WHO’s Market Information for Access to Vaccines database has allowed middle-income countries to share market data and negotiate more equitable prices, highlighting an example of a transparency initiative that has helped increase access to essential vaccines.

The series’ authors include researchers from WHO, the Organization for Economic Co-operation and Development (OECD), the Graduate Institute in Geneva, University of KwaZulu-Natal, and Harvard University, among others.

Image Credits: BMJ, Suerie et al. Defining the concept of fair pricing for medicines.

[UN News] Kenya, Mozambique and Niger curbed different outbreaks of vaccine-derived poliovirus over the past 24 months which affected 14 children, said a senior WHO official on Monday.

Although wild poliovirus virus has not been detected in Africa since 2016, roughly 12 countries are currently facing outbreaks of vaccine-derived poliovirus.

© UNICEF/Claudio Fauvrelle
Mothers take their babies to receive vaccinations at a mobile unit in Molumbo district, Mozambique.

“Ending outbreaks in the three countries is proof that response activities along with high quality immunization campaigns and vigilant disease surveillance can stop the remaining outbreaks in the region”, said Dr. Modjirom Ndoutabe, coordinator of WHO-led polio outbreaks Rapid Response Team for the African Region.

“We are strongly encouraged by this achievement and determined in our efforts to see all types of polio eradicated from the continent. It is a demonstration of the commitment by governments, WHO and our partners to ensure that future generations live free of this debilitating virus”.

Polio is a highly infectious viral disease that can lead to paralysis.  It mainly affects children under five.

While there is no cure, the disease can be prevented through a simple vaccine.

Polio is transmitted from person-to-person and is spread through contact with infected faeces or, less frequently, through contaminated water or food.  The virus enters the body via the mouth and multiplies through the intestines.

“When children are immunized with the oral polio vaccine, the attenuated vaccine virus replicates in their intestines for a short time to build up the needed immunity and is then excreted in faeces into the environment where it can mutate”, Ndoutabe explained.

Vaccine-derived polioviruses are rare, according to WHO. They only emerge in areas where overall immunization rates are low and sanitation is inadequate, leading to transmission of the mutated polio virus via sources such as contaminated sewage.

Another 12 African countries continue to experience vaccine-derived polio outbreaks, including: Angola, Benin, Cameroon, Central African Republic, Chad, Côte d’Ivoire, Democratic Republic of the Congo, Ethiopia, Ghana, Nigeria, Togo and Zambia.

Weak routine vaccination coverage, vaccine refusal and difficulty in accessing some locations, are some of the risk factors behind these outbreaks, according to WHO.

 

Image Credits: © UNICEF/Claudio Fauvrelle.

The number of cholera cases decreased by 60% in 2018 compared to 2017. Cholera-endemic countries such as Haiti, Somalia, and the Democratic Republic of the Congo saw some of the highest reductions.

Cholera vaccination in Nigeria

“The decrease we are seeing in several major cholera-endemic countries demonstrates the increased engagement of countries in global efforts to slow and prevent cholera outbreaks and shows the vital role of mass cholera vaccination campaigns,” said WHO Director-General Dr Tedros Adhanom Ghebreyesus in a press release. “The long-term solution for ending cholera lies in increasing access to clean drinking water and providing adequate sanitation and hygiene.”

There were 499,447 reported cases and 2990 deaths in 2018, significantly lower than the 1.2 million cases and 5654 deaths reported in 2017. The country most affected by the ongoing cholera pandemic continues to be Yemen, which reported 128,121 cases and 2485 deaths in 2018, according to data collected by WHO.

However, several cholera-endemic countries saw dramatic decreases in the number of cases – including Haiti, Somalia, DRC, Zambia, South Sudan, United Republic of Tanzania, Somalia, Bangladesh, and Nigeria – thanks to the implementation of new national action plans for cholera control.

“The global decrease in case numbers we are observing appears to be linked to large-scale vaccination campaigns and countries beginning to adopt the Global Roadmap to 2030 strategy in their national cholera action plans,” said Dr Dominique Legros, head of WHO’s cholera programme in Geneva.

“We must continue to strengthen our efforts to engage all cholera-endemic countries in this global strategy to eliminate cholera.”

Nearly 18 million doses of Oral Cholera Vaccine (OCV) were shipped to 11 countries in 2018, financed in part by Gavi, the Vaccine Alliance. However, experts at WHO say that vaccination must be supplemented with efforts to improve access to clean water and sanitation. Vibro cholerae, the bacterium that causes the acute diarrhoeal infection, breeds in contaminated food and water.

Mass vaccination and water and sanitation interventions are recommended as part of the Global Roadmap strategy, which provides a three-pillar framework for national action plans focusing on:

  • Early detection and rapid response to contain outbreaks
  • A multisectoral approach integrating strengthened surveillance, vaccination, community mobilization, and water, sanitation and hygiene to prevent cholera in hotspots in endemic countries
  • An effective mechanism of coordination for technical support, resource mobilization and partnership at the local and global levels.

Image Credits: WHO.

For the first time in two decades, tobacco use is projected to decline among men in 2020, according to a new World Health Organization report on trends in global tobacco use. However, the new report does not consider trends in e-cigarette use, where use may in fact be increasing.

“For many years now we had witnessed a steady rise in the number of males using deadly tobacco products. But now, for the first time, we are seeing a decline in male use, driven by governments being tougher on the tobacco industry,” said WHO Director-General Dr Tedros Adhanom Ghebreyesus in a press release about the new report.

Based on data collected from 149 countries, global tobacco use has been steadily declining for the past 18 years, from 1.397 billion people in 2000 to 1.337 billion in 2018. But that downward trend had been primarily driven by declining use in women.  About 100 million fewer women used tobacco in 2018 as compared to 2000, and women’s use of tobacco is projected to decline further over the coming five years.

However, over the same 2000-2018 period, the number of men using tobacco actually increased by 40 million people, and males currently represent some 82% of tobacco users.

Yet over just the past year, prevalence of tobacco use in males has plateaued, and it is now projected to begin declining in 2020, the latest data shows. WHO estimates that there will be 2 million fewer male users in 2020 as compared to 2018, and 5 million fewer by 2025.

“Showing that tobacco use can be reversed gives the public health community confidence we can get back on track and meet the global targets of a 30% reduction [in smoking rates] by 2025 as compared to 2010,” Ruediger Krech, director of WHO’s Department of Health Promotion said at a press briefing.

Projections of a decline in male tobacco use for 2020 are not the same across all regions either, the WHO officials cautioned. While fewer men are expected to be seen smoking in the Americas, Europe, and Western Pacific regions, WHO’s South-East Asian region, which currently has the highest proportion of male smokers at 62.5%, is projected to see a slight increase in absolute numbers over the next five years. Numbers of male smokers are also predicted to increase in the WHO Eastern Mediterranean and African regions.

And around the world, 43.8 million children between 13-15 used tobacco in 2018. That number excludes the use of e-cigarettes and other such nicotine delivery devices, which some country specific surveys have found is on the rise in youth in countries such as the United States.

Krech credited the inroads made against tobacco use over the past two decades to increasingly strong policy measures such as: banning smoking in public places, tobacco taxation, and marketing restrictions like plain packaging of tobacco products, as well as bans on marketing aimed at teens and children.  But he said that such measures must be amplified in order to reach the global targets.

“The downwards trend in tobacco use offers a challenge to governments. We cannot be satisfied with a slow decline when over 1 billion people are still using tobacco,” said Krech. “We must dramatically accelerate tobacco control measures to protect current and future generations from tobacco.”

The Unknown Contribution of E-Cigarette Use

Another unknown involves the use of smokeless tobacco devices. Use of e-cigarettes, as welll as other electronic nicotine delivery and heated tobacco devices were all excluded from the analysis, raising questions about whether potential smokers might also be shifting away from traditional tobacco products over to such methods.

Originally marketed as smoking cessation devices, electronic nicotine delivery systems (ENDS) have gained increasing notoriety for allegedly hooking young people onto nicotine at earlier ages. According to the US National Youth Tobacco survey, one of the most comprehensive national surveys that collects data on nicotine consumption annually, the proportion of high-school students who have used an ENDS device at least once shot up to 27.5% in 2019, as compared to only 12% in 2017. Manufacturers have been accused of targeting their marketing directly towards young people, particularly by producing the nicotine liquid pods in a variety of flavors popular among teenagers.

“If there are flavors like chewing gum or strawberry, who is the target audience? Me or my grandchildren,” Krech remarked.

As for whether an increase in e-cigarette use has perhaps led to a decrease in use of other tobacco products, Krech said that WHO could not at this time “say whether that has an impact or not.”  However, he acknowledged that many tobacco smokers are so-called “dual-users” – using both combustible cigarettes and e-cigarettes.

Krech added that WHO is currently collecting data on e-cigarette use and tobacco vaping, and is planning to release a more comprehensive report on the subject in February 2020. Countries have only begun collecting nationally representative data on the use of ENDS in 2013, and currently data from 42 countries is available, with more reports coming in every day.

“There is no “safety” associated with e-cigarettes,” said Krech. “There are a lot of risks associated with e-cigarettes, and we’re going to be a bit more concrete about those risks [in the February report].”

Accelerate Actions to Decrease Tobacco Use

In terms of policy measures, the report finds a clear trend towards more stringent government policies and regulations aimed at reducing tobacco use and second-hand smoke exposures. As of 2018, 137 countries have put into place at least one of the six methods recommended by the WHO in line with guidelines of the Framework Convention on Tobacco Control (FCTC).

Some 116 of these 137 countries have seen their tobacco use rates decline since implementing the measures, which include stronger measures for monitoring tobacco use; protection against second-hand smoke exposures; quit smoking programmes; awareness raising about tobacco’s dangers; restrictions and bans on tobacco advertising, promotion, and sponsorship of activities; and increased taxes on tobacco products.

The report found that strong declines in average tobacco use prevalence were mostly seen in regions that implemented the policies. This was true for the WHO South-East Asia region, which saw reductions in tobacco use – mostly in smokeless tobacco – after all 11 countries of the region had implemented at least one policy.

“Continuing to reduce tobacco use will help save lives, nurture families, and strengthen communities,” said Krech. “We must dramatically accelerate tobacco control measures to protect current and future generations from tobacco.”

Civil society organizations agreed. Gan Quan, director of Tobacco Control at the International Union Against Tuberculosis and Lung Disease and a partner in tobacco industry watchdog STOP (Stopping Tobacco Organizations and Products), said in a statement, “The problem is that the tobacco industry continues to undermine such measures all over the world and to market their products aggressively.”

Quan added, “The data is clear: tobacco use falls when governments implement policies that are proven to encourage quitting and deter youth from starting to use tobacco.”

Image Credits: WHO, WHO global report on trends in the prevalence of tobacco use, MomentiMedia/Flickr.

After collecting a windfall of nearly US$14 billion in donor commitments in October, the Global Fund to Fight AIDS, TB and Malaria, on Wednesday published its blueprint to distribute most of the money to over 100 low- and middle-income countries worldwide, saying that allocations will increase by 23% over the next three years.

Nigeria, Mozambique and the Democratic Republic of Congo are set to receive the largest awards with over $US 890 million, $US 751 million and $US 644 mllion respectively. according to the  allocation plan published on the Global Fund website. Tanzania, Uganda, South Africa, Malawi, India and Zimbabwe would receive allocations of $US 500-US $600 million each,  followed by grants ranging from tens of million to several hundred million dollars each to other qualifying African, Asian and Latin American countries, as well as Russia and former Soviet Union states. The allocation amounts represent threshholds against which countries then apply for final funding in one or all of the disease categories.

The country allocations total some US$12.71 billion, the agency said in a press release, adding, “The funds will help save 16 million lives, cut the mortality rate for the three diseases in half and get the world back on track to end the epidemics of AIDS, tuberculosis and malaria by 2030.”  In addition, countries can also apply to a separate fund of US$890 million for so-called “catalytic investments” that aim to scale up specific aspects of HIV and TB prevention or treatment, as well as strengthening health services overall.

French President Emmanuel Macron (center), and Microsoft’s Bill Gates, (far right), stand triumphantly with other Global Fund partners and supporters at the end of the successful Replenishment Drive in October that collected nearly US$14 billion in commitments.

Most eligible countries will receive funding increases, the Global Fund said. Countries in Africa are receiving around US$2 billion more than in the previous period, and countries in West & Central Africa have the biggest increase – US$780 million. Worldwide, there are 32 countries with an increase of 40% or higher.

Allocations to individual countries are calculated using a formula that is predominantly based on each country’s disease burden and economy, and then further adjusted to account for “important contextual factors”, the press release stated.

The aim is to drive funding to: “higher burden, lower income countries, specifically accounting for HIV epidemics among key and vulnerable populations, the threat of multidrug-resistant TB, and for the risk of malaria resurgence.” On the other end of the spectrum, the Global Fund aims to provide “sustainable and paced reductions where funding is decreasing” in middle and upper middle income countries that have made significant inroads in reducing disease but still require support.

“World leaders came together at our Replenishment and made commitments to step up the fight to end these epidemics by 2030,” said Peter Sands, Executive Director of the Global Fund, in the press release. “Now the real work begins. Our allocations will allow partners to expand programs that work, and to find innovative solutions for new challenges. In addition to more money, we need better collaboration and more effective programs.”

The Global Fund’s 2020-2022 allocation methodology is geared toward increasing the overall impact of programs to prevent, treat and care for people affected by HIV, TB and malaria, and to build stronger health systems, the press release stated. “The allocations provide significantly more resources for the highest burden and lowest income countries, while maintaining current funding levels or moderating the pace of reductions in other contexts.”

The allocations include increased investments in Eastern and Southern Africa for HIV prevention among adolescent girls and young women; more funding for the countries with the highest burden of TB in Africa and Asia; continued investments in Eastern Europe to cover the costs of treatment for multidrug-resistant TB; more funding for African countries with a high burden of malaria, and increased focus in the Sahel region to boost vector control and seasonal prevention campaigns.

The full list of allocations is available on the Global Fund website, along with a detailed explanation of the allocation process. In the next step of the funding process, countries convene coordinating committees to prepare and submit funding requests to the Global Fund for review and approval of the grant allocations, which may be disbursed to government as well as non-governmental funding recipients and partners.

 

Image Credits: The Global Fund.

Novartis has relinquished a patent granted by the European Patent Office for Kymriah, a promising new gene therapy for certain forms of leukemia, claiming the patent was no longer essential to the development and marketing of the treatment. The decision followed the moves by the Swiss-based NGO, Public Eye and the French-based Doctors of the World/Médecins du Monde to contest the patent in the European Patent Office. Their opposition, filed in in July, claimed that the price of the innovative therapy was “exorbitant” – with one infusion of the therapy costing CHF 370,000 in Switzerland.

Frozen T-cells of cancer patients are genetically modified to attack cancer cells in novel CAR-T therapies.

Kymriah, one of the first CAR-T [Chimeric antigen receptors T cell] therapies to receive marketing approval in Europe, is specifically designed for treating relapsing or treatment-resistant forms of acute lymphoblastic leukemia (ALL). It was developed by the University of Pennsylvania and later licensed exclusively by Novartis. CAR-T cell therapies rely on an innovative process in which a patient’s own T cells, which are critical to the body’s immune system, are collected and genetically modified to target cancer cells more effectively, and then reinfused back into the patient to attack the cancer.

The Kymriah treatment is so far being used in a limited number of patients, for instance about 100 people a year in Switzerland.  However, the underlying technology of CAR-T therapy holds much promise for treating other kinds of cancer as well. This could mean a rapid increase in the demand for similar therapies in the near future. Thus, the decision on the “patentability of such procedures” is “crucial” for setting a precedent, Public Eye said in a July statement about the patent opposition.

In a letter to the European Patent Office dated 29 November, representatives for Novartis and the University of Pennsylvania, requested the revocation of the patent on the grounds that “the proprietor no longer approves the text on the basis of which the patent was granted, and will not be submitting an amended text.”

The unexpected move was welcomed by Public Eye and Médicines du Monde, who had prepared for a long fight after they officially filed an opposition with the European Patent Office in July on the grounds that the “subject-matter lacks novelty.” The NGOs said the patent would pave the way for the Swiss pharma company to claim broad, exclusive rights not only over Kymriah, as such, but over other CAR-T cell technologies on the European market. Surprisingly, the patent holders submitted a request to withdraw the patent before the opposition procedure had in fact begun.

In response to the recent patent revocation request, Public Eye said in a statement, “This volte-face confirms that the patent should never have been granted in the first place, given that the underlying technology is not novel. It also questions the validity of other patents on Kymriah and weakens the monopoly position of the Swiss giant in future price reviews.”

The NGO added that the revocation should benefit an initiative by a number of leading Swiss university hospitals, among others, “to develop similar but considerably cheaper cancer therapies.”

In the patent revocation letter, Novartis and the University of Pennsylvania’s representatives claimed that the opposition’s arguments were “without merit.”

“[We] strongly believe in the importance of intellectual property rights as an incentive for ground-breaking innovation such as Kymriah. However, the opposed patent is not critical to the continued developement and marketing of Kymriah and the decision has therefore been taken to withdraw the opposed patent,” a Novartis spokesperson was quoted as saying to the Swiss online journal, swissinfo.ch.

Last September, Novartis also dropped a second patent application for another aspect of the treatment. However, Novartis does hold a patent on Kymriah, as such, in Europe and elsewhere. Experts in intellectual property law say that this patent still protects Novartis against the production of identical versions of Kymriah by competitors.  However, withdrawal of the other two patents leaves open a wider door for competitors to lower costs with the advance of further CAR-T innovations.

Image Credits: Novartis, Novartis.

The number of new Ebola virus cases in the ongoing outbreak in the Democratic Republic of the Congo shot up to 27 confirmed cases in the last week, triple the number of 9 confirmed cases reported between 27 November to 3 December. The recent surge in cases comes in the wake of insecurity and a series of violent attacks on Ebola workers that froze the response.

“Since the beginning of the response, there is a factor that we cannot control – the context of the intervention, including insecurity,” Michel Yao, incident manager for the World Health Oganization’s Ebola Response in the DRC said at a press conference (translated from French). “In the zones [where cases are arising], there is one particular zone, Lwemba [in Beni Health Zone], that we have not been able to access for three weeks.”

Ebola vaccinators return to Biakato Mines following a deadly attack on healthcare workers in the area on 27 November.

According to the latest WHO Disease Outbreak Notice, most cases in the past week have arisen from Mabalako and Beni Health Zones, where the Ebola response seems to be mobilizing again after temporarily scaling back activities in the last two weeks of November due to violence and riots in those affected areas. Some 18 cases were reported from Mabalako, and 6 cases from Beni, and the remaining 3 cases originated from Mandima and Oicha. Six of the confirmed cases were health care workers – including 5 traditional practitioners – representing a spike in the number of health care workers infected in the outbreak.

Despite the surge, WHO says that the average proportion of contacts under surveillance in the last seven days has returned to normal levels, and the investigation of alerts has also been improving. To ensure continued care, WHO has mounted a limited daily helicopter “air bridge” operation to transport epidemiologists to investigate cases, but to also primarily send vaccinators to hard-to-reach communities. Dr Yao noted that the communities had come to the Ebola responders seeking help.

They “want the intervention”, he insisted, “but around we have armed groups that prevent us from reaching these communities…We’re mobilising communities all around to come and get vaccinated in a situation where there are (health) alerts but we can’t go to investigate because access is restricted.”

On Thursday, the first Ebola vaccinators returned to the Biakato Mines Area, where three Ebola responders were killed in late November, to continue fighting the outbreak.

So far, 17 of the new cases have been linked to one individual – who reportedly presented with EVD illness for the second time within a 6-month period. According to WHO, rare cases of relapses of Ebola, in which a person who has previously recovered from EVD gets symptoms again, have been recorded. However, DRC officials are also investigating the possibility of reinfection – a scenario in which an individual who has recovered from Ebola gets infected with EVD from another person – which has never been documented before.

Previous studies have shown that Ebola survivors can develop immunity to the disease which can last for over a decade, but experts have long been concerned about the possibility of relapse or reinfection. The possibility of relapse or reinfection could indicate a need to revisit the kind of care provided to survivors, and how Ebola survivors are involved in future response activities.

Image Credits: Twitter: @DamelSoceFall.