‘Playing with the lives of HIV patients’: Drug shortages force many to change medication regime

Taking available medicines instead of what has been prescribed could lead to drug resistance and even death.

Source: the Scroll, 1 July 2022

Nongmeikapam Dusmanta, a retired government employee from the water resources department in Manipur, has battled with HIV, or human immunodeficiency virus, for over two decades.

He has seen the evolution of India’s battle against AIDS – acquired immune deficiency syndrome, an HIV-led disease that severely damages the immune system – from a time when there were no free diagnostics or treatment for it, to the setting up of antiretroviral therapy in 2004, and the hurdles that followed it.

But never before, he said, has the struggle been so hard. In Imphal where he lives, the antiretroviral centre at the Regional Institute of Medical Sciences is asking patients to switch to another drug regimen after crucial HIV drugs have run out of stock in government centres.

Dusmanta has refused.

The 67-year-old requires a combination of four drugs: abacavir, lamivudine, ritonavir and lopinavir.

Instead, the antiretroviral centre, which provides free medicines under the government’s National AIDS Control Programme, is giving him three other drugs: tenofovir, lamivudine and dolutegravir, or TLD in short.

“They are asking me to take another medicine without assessing whether it will work on me,” he said. “How can I take it?

Dusmanta stopped medication for a week this month. Then, worried by a possible rise in viral load, he purchased abacavir, lamivudine, ritonavir and lopinavir from a local chemist. That has meant a monthly expense of Rs 1,400 from his limited pension. “I have no option. I don’t know how long this stockout will continue,” he said.

Haobam Nanao, an HIV-infected person and a health activist, who is himself struggling to get lopinavir and ritonavir drugs, said Dusmanta is not alone. “There are many more in Imphal and not everyone can afford to buy medicines,” he said.

Rani Ngangbam, a staffer at the government-run Regional Institute of Medical Sciences in Imphal, said that at least 20 HIV-infected patients at their antiretroviral centre have had to move from their previous drug regimen to the TLD combination. “This has confused patients. Several have started skipping medicines,” she said.

Expressing helplessness, she added, “What can we do? NACO asked us to change the regimen.” NACO refers to the National AIDS Control Organisation, which works under the Ministry of Health and Family Welfare and is tasked with providing testing kits, medicines and lifelong support to HIV patients.

NACO directive

India has 23.19 lakh HIV-infected people, according to an estimate in the latest NACO report. While Maharashtra, with 3.90 lakh, and Andhra Pradesh, with 3.03 lakh, have the largest populations of infected people, states in the North East have the highest prevalence of HIV.

Since December, NACO has stopped the supply of certain antiretrovirals due to a delay in the procurement process, as reported by Scroll.in on June 28.

On May 30, Dr Anoop Kumar Puri, NACO’s deputy director general, issued a letter to all state project directors asking them to change the regimen of patients “to tide through the crisis situation as an interim arrangement”. Antiretroviral centres have since started switching HIV patients to different drug regimens wherever supply is not available.

The NACO letter said the recommendation was based on consultation with experts. Dr Ishwar Gilada, who is part of a NACO’s advisory group on treatment, said the change in the treatment regimen is temporary.

“It is better to provide some medicine than not provide anything at all,” said Gilada. “It is not going to kill them or put them in hospital, patients should shed that fear.”

Manoj Pardeshi, associated with the National Coalition of People Living with HIV in India and a member of a technical research group that advises NACO, said they are shocked that the treatment regimen was changed as a solution to the shortage of medicines.

“The change in regimen is not ensuring that the viral load reduces,” said Pardeshi. “They are doing it for the sake of doing it so that patients don’t start protesting outside ART centres.”

Puri declined to offer a comment.

Changing a drug regimen

The drug regimen of an HIV-infected person is based on his viral load, or the amount of virus in the body, and the CD4 count, which are the white blood cells that fight an infection. An HIV-positive patient has to take medication every day based on these two parameters.

Dropping the treatment may result in a rise in the amount of virus in the body and the failure of the immune system to fight it leading to death. An ideal outcome of a course of treatment would be a reduction in viral load and an increase in the CD4 count.

If a particular drug does not suit a person or if they are resistant to it, the viral load will continue to mount and CD4 count will drop below 500. That is called treatment failure and is a key indicator to change medication. A patient on first-line drugs will switch to more potent drugs called second-line, or from the second-line to the third-line of medication.

Other reasons for changing the treatment regimen could be toxicity due to a particular drug, heavy side effects or a comorbidity.

In India, despite pressure from states, the Centre is yet to introduce a testing facility, on the lines of the National Tuberculosis Elimination Programme, to check for resistance against a particular antiretroviral in an individual.

Only private clinics and hospitals have this facility in India. Under the government programme, if a patient’s viral load keeps increasing, the entire regimen, comprising two to four drugs, has to be changed since it is not possible to identify which particular drug the patient is resistant to.

Dr Shrikala Acharya, additional project director of the Mumbai District AIDS Control Society, said, “But if a regimen is helping a person get virally suppressed, then it should not be changed.”

“By changing it, we expose them to multiple drugs and pose a risk of resistance to newer drugs,” she explained.

In the current situation, patients who are responding well to medication have been forced to take a new set of medicines due to the shortage.

In Meghalaya, 45 children suffering from HIV in the East Khasi Hills were forced to take the second-line regimen although they were on the first-line of medication, said Barry Leslie Kharmalki, who works with Meghalaya State Network of Positive People.

“They all needed dolutegravir but since there is no supply, the ART [antiretroviral] centre gave them lopinavir and ritonavir,” he said. Kharmalki said both medications are used in second-line treatment. “…Nobody is looking at what harm these drugs can cause on kids.”

Dr Gautam Bhansali, a physician with the privately-run Bombay Hospital, said that under the current circumstances, switching to other antiretrovirals in the same class of drugs is acceptable after checking medical parameters such as renal and liver function, x-ray, serum creatinine levels and tolerance to drug toxicity. “If ART centres are not checking these parameters, then changing the regimen can be harmful for a patient,” he said.

Activists and patients from multiple states, however, told Scroll.in that no such clinical assessment is being carried. This amounts to “playing with the lives of HIV patients,” Kharmalki said.

Patients responding well to first-line drugs have been put on more potent second-line medicines while those already resistant to the first line of mediation have had to revert to it due to the shortage.

“Patients on the second line are already resistant to first-line drugs. If they are given the first line it will not have any effect,” said Kharmalki.

According to him, several antiretroviral centres in Meghalaya did not even inform patients before shifting them to other drug regimens. “People going to government centres are mostly uneducated. They don’t even realise their regimen has been changed,” he said.

On February 7, the Meghalaya State Network of Positive People filed a complaint with state AIDS control society over shortage of Dolutegravir and transition of children to other regimen. In its response on February 11, the latter said the replacement is “temporary” and the same regimen will restart once medicines are available.

Monitoring outcome

Despite the concerns, several patients have had to change their medication and there are conflicting opinions on the effect of such a move.

Dr Gilada, the first to start an AIDS clinic in India in Mumbai’s JJ Hospital, reasoned that NACO’s desperate move to switch to an alternate regimen is aimed at providing respite to patients until a fresh supply of medication is available.

“In the past, when regimens have been temporarily changed, the viral load has not increased,” said Gilada. “If regimen is permanently changed, then there is some impact.”

But Pradeshi, from National Coalition of People Living with HIV in India, said to check whether an alternate regimen is reducing viral load, they will have to wait for a few months to test. “ We are putting patients at risk.”

Jahnabi Goswami, who works with HIV-infected people in Assam, said the government needs to plan in advance to prevent such a situation. “Nothing about how they are handling patients is right,” she said.

Goswami said the network of which she is a part of, plans to check the viral load of patients, whose treatment regimens have been changed, in a few months to understand the outcome.

Runjun Dutta, attached with Médecins Sans Frontières access campaign, said, the government must have a strong reason to change regimen. “And bureaucratic delays that cause supply mismanagement is not a justifiable reason,” said Dutta. “Unfortunately it has become a common excuse for NACO in the last few years.”

Treatment drop out

Activists who work with HIV-infected individuals fear the drug shortages may eventually lead to their worst nightmare: patients dropping out of treatment.

Nalinikanta Rajkumar, president of the Manipur-based Community Network for Empowerment, said he anticipates a high treatment drop-out rate due to the supply problems. “Some patients are buying medicines from their own pockets, and some have stopped taking medicines altogether,” he said. “The government is failing to adhere to the 90:90:90 target.”

The 90:90:90 target has been set by the United Nations Programme on AIDS for countries to control the disease. It means that 90% of those who have HIV will know their status by 2020 and 90% of those diagnosed with HIV will receive antiretroviral therapy, and 90% of those on therapy will have some viral suppression.

Roshan Maisar, associated with the non-profit Saathii that works with the government in the field of HIV across India, said the medication is for life and patients often struggle to take it every day. “They need a lot of counseling for treatment adherence,” said Maisar. “They may drop out if medicines are not available.”

A 44-year-old-patient in Nagpur, who did not want to be identified, said he has reached that point. “I feel I am an experiment for them.”

He has been running around for antiretrovirals since February. He is on a third-line drug regimen comprising Ritonavir, Lopinavir and Dolutegravir.

In February, he purchased medicines for 15 days when the antiretroviral centre had no stock. “These drugs are expensive,” he said. “After my medicines got over, I began visiting different NGOs for help.”

Some non-profits managed to provide him stock through a government centre, but they were paediatric medicines, not adult ones. “Paediatric medicine is 125 mg per dose. I had to take four pills per day to ensure adult dosage,” he said.

By April, even the non-profits could not help him. “I started taking a gap of two to three days between pills to last them longer,” he said.

Earlier this month, the ART centre told him that ritonavir, lopinavir and dolutegravir were not available and that his medication was being changed to a combination of atazanavir and ritonavir.

He said he told the centre that he had taken those drugs in the past but they did not work. “My haemoglobin levels had fallen due to those drugs. There were other patients who were complaining too,” he said. “But the ART centre said they have received instructions from NACO to do this.”

He is back to the old treatment regimen that he knows very well does not work for him. “I am taking it in the hope that it has some effect on my body,” he said.

This is the second part of a series on HIV drug shortages. Read the first part here.

Posted in Access to Medecines, HIV/Aids | Leave a comment

Pfizer’s Covid pill Paxlovid gets WHO’s approval. All you need to know 

Coronavirus disease (COVID-19) treatment pill Paxlovid  (REUTERS)

The WHO recommended Paxlovid over remdesivir, as well as over Merck’s molnupiravir pill and monoclonal antibodies.

Source: Mint

The World Health Organization(WHO) said that it “strongly recommended” Pfizer’s Covid-19 antiviral pill Paxlovid for patients with milder forms of the disease who were still at a high risk of hospitalisation.

Pfizer’s antiviral pill: All you need to know 

Pfizer’s oral antiviral drug (a combination of nirmatrelvir and ritonavir tablets) is strongly recommended for patients with non-severe COVID-19 who are at highest risk of developing severe disease and hospitalization, such as unvaccinated, older, or immunosuppressed patients.

WHO’s recommendation is based on new data from two randomized controlled trials involving 3078 patients. The data show that the risk of hospitalization is reduced by 85% following this treatment. In a high-risk group (over 10% risk of hospitalization), that means 84 fewer hospitalizations per 1000 patients.

WHO has strongly recommends that Pfizer make its pricing and deals more transparent and that it enlarge the geographical scope of its licence with the Medicines Patent Pool so that more generic manufacturers may start to produce the medicine and make it available faster at affordable prices.

The WHO recommended Paxlovid over remdesivir, as well as over Merck’s molnupiravir pill and monoclonal antibodies.

Patients must start taking their Paxlovid pills within five days of the onset of symptoms — the course then lasts five days.

WHO has also updated its recommendation on remdesivir, another antiviral medicine.

Previously, WHO had suggested against its use in all COVID-19 patients regardless of disease severity, due to the totality of the evidence at that time showing little or no effect on mortality. Following publication of new data from a clinical trial looking at the outcome of admission to hospital, WHO has updated its recommendation. WHO now suggests the use of remdesivir in mild or moderate COVID-19 patients who are at high risk of hospitalization.

Posted in Access to Medicins, COVID-19, Drugs, Generics, Vaccines | Tagged , , , | Leave a comment

Cutting Edge: After Covid, can genome sequencing help identify gene responsible for drug-resistant TB?

Tuberculosis is the leading infectious disease killer in the world and was only recently overtaken by Covid-19. Scientists are keen on exploring whole genome sequencing (WGS) for TB investigation.

The Mtb transmissibility may vary between lineages (or variants) and this may contribute to the slow decline of tuberculosis (TB) incidence,” Dr Karyakarte explained.

Source: Indian Express

In the past two years, genome sequencing enabled scientists to rapidly identify the SARS-CoV-2 virus and its variants. Now, can the gains made during the Covid-19pandemic be expanded to more uses and help frame public health responses for other infectious diseases such as tuberculosis — which India hopes to end by 2025? Taking a lead in this direction is the Pune-based B J Medical College and Sassoon General Hospital, which plans to utilise their year-old genome sequencing facility to identify genes responsible for drug-resistant TB.

Tuberculosis is the leading infectious disease killer in the world and was only recently overtaken by Covid-19. Compared to 2019, tuberculosis cases in 2020 reduced by 18% globally (from 7.1 million to 5.8 million cases) and by up to 24% in the ten worst-affected countries with high tuberculosis burden, as per the new Lancet Respiratory Medicine series published on March 23 this year.

Scientists are keen on exploring whole genome sequencing (WGS) for TB investigation and this concept further got a fillip when a joint study by BJMC with Johns Hopkins University School of Baltimore, USA, and others, highlighted the need for increased surveillance of TB antibiotic resistance in India. Findings of their study that compared transmissibility across four major lineages (L1-4) of Mycobacterium tuberculosis (Mtb) has shown that there are inherent differences between the lineages with implications for TB control, surveillance, and monitoring.

Published recently on medRxiv, the pre-print server for health sciences, the study showed that modern Mtb lineages (L2 and L4) were more recently introduced in Western India, compared to older lineages (L1 and L3). L2 shows a higher frequency of drug-resistance as well as higher transmissibility.

“Our findings highlight the need for contact tracing around cases of TB due to L2, and heightened surveillance of TB antibiotic resistance in India,” said Dr Rajesh Karyakarte, coordinator of Maharashtra’s genome sequencing project and head of the department of microbiology at B J Medical College and Sassoon General Hospital, the largest government hospital in Maharashtra

“While there is geographic variation in the lineage prevalence, L1 comprises approximately two thirds (67%) of the Mtb isolates in the country. However, all four major lineages are found in circulation. The Mtb transmissibility may vary between lineages (or variants) and this may contribute to the slow decline of tuberculosis (TB) incidence,” Dr Karyakarte explained.

Health |With khichdi, tiranga paratha and sesame laddu, Gadchiroli’s severe malnourishment cases drop by 50%

“As modern and more drug-resistant lineages take further hold in India, the proportion of TB with drug resistance may continue to rise, along with the number of possible new resistance associated variants. To achieve control, resources will need to be directed towards interrupting transmission by increasing efforts towards active case finding, contact tracing, early diagnosis, and treatment. The wider adoption of WGS can assist these efforts allowing clinicians to tailor therapy sooner and in turn help decrease transmission. Hence an improved understanding of these characteristics is important to improve the ability to control TB transmission,” he said.

Whole Genome Sequencing (WGS) can be used to assist efforts in providing quicker genotype-based drug susceptibility testing (DST) results of Mycobacterium tuberculosis, and with the genome sequencing facility set up at BJMC a year ago, Dr Karyakarte and his team have been assured funding from Maharashtra government, and are set to embark on the exercise soon.

The molecular laboratory at BJMC has been extremely busy in the last two years of the Covid pandemic. From using molecular scissors to prepare DNA for sequencing machines to studying changes in the genetic structure of SARS-CoV2 virus and identifying variants, scientists were able to sequence 3,000 samples at the college itself.

As part of a memorandum of understanding with IISER, NCL and Pune Knowledge Cluster, they sequenced more than 10,000 samples. Every month, the BJMC coordinated the collection of 100 samples from each of Maharashtra’s 36 districts and sent it to the Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology as part of a state project for genome sequencing.

Analysing results and reporting it to the state government, the National Centre for Disease Control and Indian SARS-CoV-2 Genomics Consortium soon became a norm, and it was through the genome sequencing project at BJMC that it was confirmed that the Omicron variant had arrived in the country in December and not November 2021.

“We are ready to use this methodology to detect more genes responsible for drug resistant TB,” Dr Karyakarte said. Scientists at the laboratory also suggest that just as Indian companies (aided by the Department of Biotechnology, Government of India) devised probe and primer sets for Covid, the same could be done for rapid identification of TB. “The government can procure them in mission mode and distribute them to 877 Indian Council of Medical Research approved laboratories across India for diagnosis of TB,” he said.

India, Indonesia, the Philippines, and China have together seen a reduction of 1.3 million cases (93%) in tuberculosis; and major reductions in notified cases have been seen in the Philippines (37%), Indonesia (31%), South Africa (26%), and India (25%). In 2019, India notified 2 1,76, 677 cases of TB to the World Health Organisation, while in 2020 the drop was significant — only 16,29,301 cases of TB were notified.

Data from Maharashtra — among the states with a high burden of TB — shows that over 2.27 lakh new cases were notified in 2019. There was a significant drop in 2020 (1.6 lakh new cases of TB) owing to the Covid pandemic. The figure rose to 2 lakh in 2021 as efforts to detect active TB cases intensified. Last year, Maharashtra reported 9,445 multi-drug resistant TB cases and 254 Extremely drug resistant (XDR) TB cases.

Posted in COVID-19, Diseases/Therapies, Drugs, Generics, Tuberculosis (TB) | Tagged , | Leave a comment

The Covid treatment pill is here – and big pharma will ultimately decide who gets it

Experts are predicting demand for life-saving antiviral drugs will rapidly outpace supply. Like the vaccine, the poorest countries will be left until last

Paxlovid is manufactured in Freiburg, Germany, December 2021. Photograph: Pfizer Inc. Handout/EPA

Source: The Guardian

Covid-19 has quietly become the gift that keeps on giving for big pharma. The past two years has seen it reap huge profits from Covid vaccines, while simultaneously opposing wider sharing of the technology required to make them. And now there’s a new money-spinner on the rise: Covid antiviral treatment pills. Once again, we’re poised to fall into the same inequality traps we’re caught in with the global vaccine rollout.

Both Pfizer and Merck have new antiviral pills rapidly arriving on the market – Paxlovid and molnupiravir respectively. As with the vaccines that came before them, both corporations have made it their business to ultimately decide who gets to make generic versions through the medical patent system – a crucial, life-saving question for millions around the world.

And business certainly looks promising. Pfizer alone, freshly cemented as the global Covid-19 vaccine kingpin, expects to make as much as $22bn from its new pill this year, on top of $37bn it made in 2021 from the vaccine.

The new medication isn’t coming cheap. Pfizer’s Paxlovid currently costs about $530 for a five-day course of the treatment. Merck’s molnupiravir, now approved for use in the UK, costs about $700. Reportedly, the cost of production for molnupiravir stands at about $17.74.

Familiar alarm bells should be ringing. Experts across the board are predicting demand for antiviral drugs will rapidly outpace supply. A World Health Organization report produced in January warned of a “high risk of shortages” of Paxlovid for low- and lower-middle-income countries until generic versions became more widely available, which isn’t likely to be until the second half of 2022 at the earliest. Separate analysis from the data and analytics firm Airfinity suggests that could be as late as early 2023. After an uneven global vaccine rollout, lower-income nations are faced with the prospect of a “wild west” scenario for life-saving pills, too.

Pfizer and Merck have chosen to designate a select few generic manufacturers able to produce cheaper versions of their drugs, through the Medicines Patent Pool (MPP). But even with these deals in place, they remain firmly in control, and access to generic versions are within reach of only half the world’s population.

A number of countries including Argentina, Brazil, Thailand, Russia, Colombia, Peru, Turkey and Mexico have again been excluded from such licences and are left to try to cut deals for the most expensive products. With so many priced out of the market, global supply will again be prioritised to rich countries, while the companies refuse to make affordable generic antivirals available to everyone wherever they are needed.

This is a grim mirror of the dramatically uneven vaccine supply earlier in the pandemic, when rich nations bought up many more doses than they could use. The US, where almost two-thirds (65%) of the population is already fully vaccinated, has reportedly put up more than $10bn for Pfizer’s Paxlovid – more than twice the entire GDP of Sierra Leone, where just 9% of people have the same protections. For less wealthy nations, competition isn’t even a possibility.

Meanwhile, Merck continues its “evergreening” patent strategy to extend its monopoly on molnupiravir beyond the standard 20-year protection. Since developing the pill, it has sought at least 53 patent applications to tie it up in legal red tape and stay firmly in control of who gets to make it and where. It has already received emergency approval in the US and Japan, and has been given the green light in the UK.

Even in nations within the MPP, where the pills are allowed to be made by select manufacturers, a low cost is not guaranteed. Dr Reddy’s Laboratories in India has made a generic version of Merck’s pill that costs $18 for a course of treatment. However, these costs won’t necessarily be reflected everywhere. Across the border in Bangladesh, the generic version of Pfizer’s pill will cost more than $170 for a course of treatment – prohibitively expensive for a huge number of the population. By restricting which manufacturers may produce a generic version, firms maintain considerable control over the final price. In the past, Gilead’s treatment for hepatitis C, sofosbuvir, only dropped in price consistently when the number of manufacturers was increased without these limits.

There is an uncomfortable assumption those in the global north have tacitly begun to accept. When the demand is higher than supply, there is a pecking order: rich nations first, buying up more than they realistically need, while the poorest are forced to scramble to outbid each other over what is left, dramatically overpay, or just wait until they’re affordable and watch death tolls rise. But this supply crisis is entirely artificial. We could produce more – Pfizer and Merck’s drugs are not complex, and could be easily manufactured in a wide range of developing countries if they had access to the knowhow and could avoid the threat of legal action. We need patents and other intellectual property barriers on life-saving medicines to be waived – either voluntarily by companies, or by government decree – so we can quickly supply all countries of the world.

We’re doubling down on a two-tier world when it comes to Covid-19 – rich, highly vaccinated nations with easy access to both preventive measures and treatments, and poorer nations trying to get by without either. It’s vital that we don’t sleepwalk into giving corporations so much control over who gets to live and who gets to die, all balanced on what they deem an acceptable bottom line.

Posted in Access to Medecines, Access to Medicins, Antibiotics, COVID-19, Diseases/Therapies, Drugs, Generics, Vaccines | Tagged , , , | Leave a comment

Pandemic puts a global spotlight on IP, as countries step-up efforts to be heard

Leaders of the European Union (EU) and African Union (AU) at the summit in Brussels, Belgium on February 18, 2022, where African leaders reiterated their call for a waiver of Intellectual Property rights.

Source: The Hindu Business Line

Experts call for more from India, a key voice in the past

Last Friday, the African Union marked a milestone as technology to make mRNA vaccines now prepares to roll-out from the world’s first mRNA hub to six countries on the continent. The World Health Organization-supported initiative, along with European partners, aims at getting Africa to produce vaccines for the latter, and more. 

The high-profile summit in Brussels to announce this was attended by Presidents from all countries receiving the technology– Egypt, Kenya, Nigeria, Senegal, South Africa and Tunisia, the WHO chief Dr Tedros Adhanom Ghebreyesus, the European Commission President, Ursula von der Leyen and French President Emmanuel Macron.

But it comes against the backdrop of a call to waive Intellectual Property (IP) on Covid-19 tools, during the pandemic – a proposal mooted by India and South Africa. Quite naturally, the summit reflected the familiar tones that the IP waiver discussion has been witnessing over the last several months. The African leaders reiterated their call for a waiver and the European representatives maintained, IP was not a barrier, if technology transfer could be achieved through such initiatives. 

In fact, IP was centre-stage last week in another geography as well, with the deadline closing for submissions to the United States Trade Representative (USTR) office, ahead of its Special 301 report. The report is a scorecard of sorts, rating countries on their IP enforcement efforts. India, along with a clutch of other countries, is on its “priority watch list”.

The pandemic has put IP on a global stage and in full public view. But it’s unclear how it will all pan out for India, which until now has been a front-foot player on these issues. 

Having witnessed India’s participation in the international IP arena over the years, Dr Biswajit Dhar, professor of economics, Jawaharlal Nehru University, observes that matters have come a full circle on the call for an IP waiver.

“At the end of the day, ….we have no fall back position,” he says, indicating that India should have played a way more proactive role during the pandemic, in supplying vaccines and medicines. Public health experts agree, India should have resumed vaccine exports, for example, earlier than it did after the coronavirus-induced second wave.

US discussions

In its submission to USTR, the Indian Pharmaceutical Alliance (representing large domestic drugmakers) calls for taking India out of the Priority Watch List. “India is fully compliant with the multilateral TRIPS agreement and continues to take steps in accordance with international trends and progress,” it said.

But the PhRMA submission (representing multinational drugmakers) pointed out, India’s policy environment is unpredictable, with legal and regulatory systems posing “procedural and substantive barriers at every step of the patent process…”

Complementary role

Taking a birds-eye view of the different global IP developments, observers laud Africa’s efforts to establish vaccine production capacities, but wonder if India is at risk of losing some of its sheen as a reliable supplier to the world.

Leena Menghaney, Global IP advisor for MSF Access Campaign, observes that the India-South Africa proposal on the IP waiver was a gamechanger and did push big pharma to pursue partnership strategies.

India has the capacities for medicines, vaccines and diagnostic reagents, she points out. As a result, India can regain some of its lost ground (as reliable partner) by playing a complementary role to the African initiative, given its strengths in making APIs (Active pharmaceutical ingredients) or lipids (for mRNA vaccines) etc. 

On the USTR report, she adds, the US should have suspended the exercise, at least on pharmaceuticals, during the pandemic. 

Instead, the turf just got more combative. PhRMA says, its members inked about 300-odd partnerships on Covid-19 products. “Multilateral organizations that once served as custodians of the international rules based system increasingly are seeking to undermine and even eliminate intellectual property protections that drive and sustain biopharmaceutical innovation…. ,” they point out.

The coming months will see increased international activity on IP. And public health experts are calling for India’s voice (as a critical pharmaceutical producer) to be heard, a little louder.

Posted in Antibiotics, COVID-19, Diseases/Therapies, Organizations, Right to Health, Vaccines, WHO | Tagged , , | Leave a comment

Cipla to launch oral anti-viral covid drug Molnupiravir in India 

Molnupiravir, an antiviral drug, will be manufactured for restricted use under emergency situation for the treatment of adult patients with COVID-19 and who have a high risk of progression of the disease


Cipla Limited on Tuesday announced that the drug maker has been granted Emergency Use Authorisation (EUA) permission by the Drug Controller General of India (DCGI) for the launch of Molnupiravir in the country. Cipla plans to launch Molnupiravir under the brand name Cipmolnu. 

Molnupiravir is the first oral antiviral approved by the UK Medicines and Healthcare products Regulatory Agency (MHRA) for the treatment of mild-to-moderate COVID-19 at high risk of developing severe disease.

Earlier in the year, Cipla entered into a non-exclusive voluntary licensing agreement with Merck Sharpe Dohme (MSD) to manufacture and supply Molnupiravir in India and to over 100 low and middle-income countries (LMICs). The regulatory approval comes on the back of a five-month collaborative trial conducted by a consortium of companies.

“Cipla will soon make Cipmolnu® 200mg capsules available at all leading pharmacies and Covid treatment centers across the country. The Company has adequate manufacturing capacities and a solid distribution mechanism in place to ensure speedy access to this effective treatment pan India,” the company informed in an exchange filing on Tuesday.

Earlier today, Central Drugs Standard Control Organisation (CDSCO) approved the Serum Institute of India’s COVID-19 vaccine Covovax, Biological E’s jab Corbevax and anti-Covid pill Molnupiravir for restricted use in emergency situation, announced the Union Health Minister Mansukh Mandaviya.

A meeting of the SEC was held on Monday to review the applications for granting approval to the new vaccines and the antiviral drug.

“Molnupiravir, an antiviral drug, will now be manufactured in the country by 13 companies for restricted use under emergency situation for treatment of adult patients with COVID-19 and who have high risk of progression of the disease,” Mandaviya said.

Posted in COVID-19, Diseases/Therapies, Drugs | Tagged , , | Leave a comment

Shortage of key TB drug stress patients; activists urge govt to issue compulsory license

Source: TimeOfIndia

MUMBAI: Stockouts are being reported across the country of a key patented drug, Delaminid, used in drug-resistant tuberculosis (DR-TB), hampering the government’s goal of TB elimination and causing hardship to patients.

Much worse, the procurement of the drug in still pending as negotiations with the Japanese patent holder Otuska are stuck due to the high price, health activists told TOI.

India has the highest burden of DR-TB, accounting for about one-fourth of the global burden. Among them are the most difficult to treat. XDR-TB (extensively Durg-resistant TB) cases.

The proposal to supply Delamanid at $1275 (approximately a lakh) per course is yet to be cleared, even though it is already Q3 of the year, health activists and TB-affected communities pointed out in a letter (click here to read more) to the Union Health Minister recently.

Ironically, the shortages are being reported, even as the government assured the Bombay High Court of sufficient supplies of the drug that is critical for an effective TB treatment.

Children with DR-TB and adult patients with XDR-TB need inclusion of both the new TB drugs, Otsuka’s Delaminid and Johnson & Johnson’s Bedaquiline to ensure an injection free, less toxic and effective regimen.

In the case filed by patients groups in March, theCentre rejected compulsory licensing for the generic supply of Delamanid, citing “available stock is sufficient to meet the requirements for the next nine months.”

The negotiations for a lower price of Delamanid with the patentee have failed and now the countrywide stock-out of Delamanid is life threatening for adult and pediatric patients with drug-resistant TB who need access to ensure a regimen that is effective. The programmatic management of drug-resistant TB (PMDT) is suffering a setback due to shortages of GeneXpert kits and Delamanid even as it had started to recover after the second wave of the pandemic. Immediate steps to ensure supplies and encourage generic competition are the need of the hour to ensure that all patients have a chance of an effective cure for DR-TB,” Leena Menghaney, lawyer working on IP and access to medicines told TOI.

The situation has become worse since May with shortages reported of essential TB drugs at several DOTS centres across the country, with hotspots like Mumbai and Delhi suffering the most. Stocks are also running thin in states like Karnataka and Uttar Pradesh, a TB activist said.

This comes in the midst of an overall worsening situations of TB globally, according to the Global Tuberculosis Report, with TB deaths in 2020 having increased for the first time in over a decade.

Delamanid is part of the WHO Essential Medicines List for the treatment of DR-TB for adults and children, and is included in India’s NTEP (National Tuberculosis Elimination Programme) guidelines on PMDT. It was recently added in the draft NLEM (National List of Essential Medicines).

A compulsory license on Delamind would allow domestic companies to offer affordable generic versions to the NTEP, helping in the scale-up of treatment, experts added.

“We also urge you to encourage generic suppliers to register the adult and child formulations of delamanid with the CDSCO so that in 2022 a similar situation of high pricing failed negotiations with the patentee, leading to stockout, can be avoided. In the circumstances, a government authorisation or a compulsory license must be issued to allow generic companies to supply delamanid to NTEP,” The letter adds.

India has approximately 1,24,000 cases of MDR-TB (multi-dug resistant) new cases every year, with about 25,000 DR-TB patients who need immediate access to better treatment regiments,. including the two new drugs.

Posted in Access to Medecines, Access to Medicins, Diseases/Therapies, Generics, Tuberculosis (TB) | Tagged , , , , , | Leave a comment

India’s antimicrobial resistance and how to solve this problem

Powerful medications are slowly becoming ineffective for many Indians due to misuse of antibiotics

Source: FreePressJournal

A recent ICMR report has left healthcare providers, patients, and infection control experts worried about the rising Antimicrobial Resistance in India. The report says that more than 50 per cent of ICU patients have been battling a type of pneumonia caused by the bacteria ‘Klebsiella Pneumonia’ and will not respond to even powerful antibiotics like Carbapenem. Another antibiotic, Imipenem, will not affect a mutated form of E-coli in three out of 10 cases. This means mutations in microbes, be they bacteria, viruses, or fungi, are rendering medicines useless when the patients most need them.

Given the pandemic and the extensive use of antibiotics to fight Covid-19, antibiotic resistance has been accelerated. Many experts are of the opinion that our approach to treating Covid-19 in hospitals could be exacerbating the problem. Having said that, India, with its combination of a large population, rising incomes that facilitate the purchase of antibiotics, a high burden of infectious diseases, and easy over-the-counter access to antibiotics — is an important locus for the generation of resistance genes. This was the state even before the pandemic hit us.

Antibiotic resistance leads to longer hospital stays, higher medical costs, and increased mortality. We have already seen the rise of secondary infections and rare fungal infections such as Mucormycosis or Black Fungus, White Fungus, and Yellow Fungus, taking a toll on Covid-19 patients during the second wave. Several studies attribute this to the injudicious use of steroids and other antibiotics medicines.

Moreover, even before the pandemic, India experienced over 56,000 newborn deaths each year due to Sepsis caused by organisms resistant to first-line antibiotics. Also, an estimated 170,000 deaths from pneumonia in children under five can be averted with timely access to effective antibiotics. While rising rates of resistant infections are a threat, many deaths are attributable to the lack of access to basic antibiotics. Another important aspect is the use of antibiotics in the poultry and animal industry. This is much larger than what we imagine and contributes to the growing menace of resistance.

The solution: We need to balance excessive and inappropriate use, a key driver of antibiotic resistance, while ensuring live-saving medicines are available to those who need them. There is also a need to improve vaccination coverage, access to clean water, adequate sanitation, and improved hygiene.

However, efforts must be made to bring about behavioural changes in terms of hygiene practices, self-medication efforts, and proper health education. Vaccination has been shown to reduce the transmission of AMR infections and the volume of antibiotics consumed due to appropriate treatments of bacterial infections and viral infections.

India has undertaken many activities like Mission Indradhanush — to address low vaccination coverage and strengthened micro-planning and additional mechanisms to improve monitoring and accountability. Yet, improvements in coverage are still needed. Moreover, antibiotic stewardship programs are very much needed to help providers and clinicians make the best clinical decisions possible for an antibiotic prescription.

Antibiotic stewardship is the systemic effort to ensure effective treatment of infections, and therefore combat AMR, by monitoring and advising on antibiotic prescription and use. Another aspect is the appropriate management of antibiotics throughout the supply chain — from manufacturing to consumption. Effluents from pharma manufacturing contain active antibiotics, resistant bacteria, and resistant genes; they contaminate rivers, streams, and wells, including water used for drinking and bathing.

This increases both the emergence of resistant bacteria in local populations and also its spread. In addition, even lower levels of contamination in wastewater can cause resistant bacteria. In the same light, researchers have noted that contamination in areas where there is an antibiotic manufacturing industry led to an increase in bacterium causing resistance to Carbapenems.

Another source of environmental contamination is contaminated hospital waste. Untreated hospital waste may contain antibiotics and resistant bacteria. Where disposal mechanisms are inadequate, such waste puts staff and patients at increased risk from AMR. Hence, a concerted approach that incorporates diverse stakeholders to tackle and control the spread of antibiotics is essential.

Posted in Access to Medicins, Antibiotics, COVID-19, Diseases/Therapies, Drugs, Generics, India, Quality, Vaccines | Tagged , , , , , | Leave a comment

AMR mitigation must top pharma industry’s agenda

To deal with this threat, the pharma sector must adopt environmentally sustainable production and supply chain measures.

Source: TheHinduBusinessLine

The economic and social consequences of the Covid-19 pandemic have reiterated the destructive capacity of untreatable infectious diseases. While we actively find various mitigation strategies to control this pandemic, we must pause to reflect on the veiled public health emergency — antimicrobial resistance (AMR), threatening public health and economies worldwide. 

Increased AMR in microbes like bacteria, fungi, and parasites diminish the efficacy of antibiotics in treating simple infections. A recent WHO-supported report has found high rates of AMR in the bloodstream and urinary tracts among the population of countries with reported data on AMR. The rising of AMR in common infections would offset medical advancements made over the years, as pre-pandemic estimates suggested AMR will induce 10 million deaths every year by 2050. It is already being discussed that the extensive use of antibiotics for clinical management of the pandemic has driven up AMR even further.

One Health Approach

Combating AMR calls for a multi-sectoral strategy nestled in the One Health Approach. Apart from the collaboration between governments and multi-lateral agencies, the pharmaceutical sector is a key player for the One Health Approach to have the desired impact. The functioning of our healthcare systems depend on sustained access to medicines. Disruptions like a pandemic or geopolitical crisis can lead to critical drug shortages and escalate adverse patient outcomes. 

While stabilising the supply chain to absorb future shocks is important, the industry must pivot towards environmentally responsible ways of manufacturing APIs and drugs in finished dosage forms. This is imperative to mitigate AMR resulting from drug manufacturing.

The Pharmaceutical Supply Chain Initiative (PSCI) has been working with industry members for excellence in safety, environmental, and social outcomes for the whole of the global pharmaceutical and healthcare supply chain. 

Recently, 51 pharmaceutical companies from various regions aligned with PSCI’s vision of holistic improvements in the supply chain. Additionally, there are 19 PSCI members with Indian suppliers and over 300 PSCI suppliers in India to propel the industry’s growth while ensuring sustainable pharma supply chains.

With support of its government, the Indian pharmaceutical sector is acting as an engine of growth. The Indian pharmaceutical industry is the third largest in value, set to be valued at around $130 billion by 2030. Additionally, the Indian Active PharmaceuticaI Ingredient (API) industry is ranked third largest in the world. Recently, the government announced a slew of policy measures and incentives for the pharma sector to leverage the industry’s growth potential with incentives for domestic production of APIs and Key Starting Materials (KSMs) and incentivisation of setting up bulk drug parks. A reassessment of environmental regulations will make the Indian pharma industry self-reliant and more sustainable. A farsighted view and approach to embrace sustainability will go a long way in increasing benefits to businesses, public health, and the economy.

Strengthening of localised manufacturing capacities is required for the supply chain to be more resilient. However, there should be equal focus on limiting the environmental impact of API and finished drug products. In the absence of laws restricting antibiotic residue concentration limits in water bodies, irresponsible production practices continue to drive environmental AMR and weaken the One-Health Approach. 

Responsible procurement and production hold more relevance as the industry expands to new geographies. Industry members must focus on long-term sustainability over short-term profits. 

The pharmaceutical industry has shaped the lives of millions world over through their medicines. However, the unsustainable procurement and production practices can offset benefits of these medicines due to increased AMR. Aided by the agencies and governments, the industry must play its role in AMR mitigation.

The writer is Associate Director- Corporate Sustainability at Centrient Pharmaceuticals, and Chair, Pharmaceutical Supply Chain Initiative

Posted in Access to Medicins, Antibiotics, COVID-19, Diseases/Therapies, Drugs, Generics, Right to Health, Vaccines | Tagged , , , , , | Leave a comment

Antimicrobial resistance is rising in India, says ICMR report.

Source: TheTimes Of India

MUMBAI: More than 50% of the ICU patients battling a type of the Pneumonia caused by bacteria Klebsiella Pneumoniae will not respond to powerful antibiotics called carbapenem. Another antibiotics, imipenem, will not affect a mutated form of Ecoli in three out of 10 cases.

These are some of the findings of Indian Council of Medical Research’s latest report on ‘antimicrobial resistance research and surveillance’ conducted between January and December 2020, which underlines the growing antimicrobial resistance across India. Mutations in microbes, be they bacterium, viruses or fungi, are rendering medicines useless when the patients most need them; experts say this has been brought about by decades of overuse and misuse of antibiotics, antifungals and antivirals.

As the Covid pandemic dominated 2020, the ICMR data collection too was hit; only 65,000 culture reports could be collected from 30 tertiary care hospitals across India as against 1 lakh samples collected in 2019. Most hospitals were closed to non-Covid patients and only the severely ill ventured to hospitals during Covid.

‘The ICMR has brought out an exhaustive AMR report for the fourth time, and while some microbes have become more resistant and other have become more susceptible (to treatment), the overall picture remains the same,” said senior ICMR scientist Dr Kamini Walia, who has been leading AMR project.

Due to Covid-19, the use of antibiotics increased and scientist fear that resistance will definitely increased in the near future. Dr Rahul Pandit, who heads the ICU in Fortis Hospital, Malund, said carbapenem resistance is evident in almost 50% of the patients. ‘When we notice carbapenem resistance, we give the patient the last resort antibiotic, colistin. We have run out of options left with us to treat patients,” Said Dr Pandit, who was not associated with the ICMR project. While colistine works in most cases, there are already stray cases of resistance being reported.

The ICMR report 2020 said five of the organisms posed a big worry: Escherichia coli (or Ecoli) was found in almost a fourth of the samples, followed by the Klebsiella Pneumoniae (18%), pseudomonas aeruginosa (12%), acinetobacter baumannii (10.4$) and staphylococcus aureus (9.6%). “The AMR trends and patterns are worrying. The Covid situation has only made the situation worse, “said Dr Walia.

In 2020 report, the Ecoli track showed an aberration:Susceptibility of Ecoli to antibiotic Imipenem that has increase from 86% in 2016 to 63% in 2019 showed a slight recovery to 72% in 2020. However, Klebsiella pneumoniae dropped from 65% in 2016 to 46% in 2019 and remained at 45% in 2020.

Acinetobacter baumannii, which causes a relatively simple infection to treat, has emerged as a worry in the past few years, accounting for almost a tenth of the samples in 2020.

Dr Pandit said the need of the hour is to hold an antimicrobial stewardship programme that will lay down stringent rules on use of these drugs. “But such programs work only in hospital settings. In India anyone can prescribe and sell an antibiotic, leading to large-scale misuse and resistance,” he said.

Posted in Access to Medecines, Access to Medicins, Antibiotics, COVID-19, Diseases/Therapies, Drugs, Generics, India, Vaccines | Tagged , , , , | Leave a comment