COVID CRISIS-A DISGUISED BLESSING FOR INDIAN PHARMA INDUSTRY!

“Never let a good crisis go to waste.”-Winston Churchill

“Every problem is an opportunity in disguise.” Taking that to the heart seems to be the road ahead for India’s pharmaceutical industry.COVID-19 has lead the industry into crisis mode, but it could just be the rude wake-up call for a silver lining in the dark and ominous COVID-19 cloud.

India’s pharmaceutical exports stood at $17.27 billion in 2018 and grew to $19.14 billion in 2019. The country’s pharmaceutical industry is expected to expand by 22.4% over 2015–20 to reach $55 billion. COVID crisis brought an apprehension about the pharma economy but it actually paved the way to leapfrog into the future. India’s Serum institute struck an agreement with AstraZeneca to manufacture 1 billion doses of coronavirus vaccine being developed by Oxford University. This has  lead the company’s wealth to grow the fastest, at $15 billion, among Indian billionaires and fifth fastest in the world during the COVID-19 pandemic.

The global crisis is potentially a blockbuster for the industry in terms of sales and profits. Cipla’s share price jumped almost 3% after the country's drug regulator approved Hetero and Cipla to manufacture and market antiviral drug remdesivir.

Also, Glenmark being knocked down in economy surged 40% in trade after the launch of drug favipiravir. There are chances of Glenmark's share to skyrocket once the clinical efficacy of drug favipiravir is established.

In view of the humanitarian aspects of the pandemic, India’s decision to lift the ban of paracetamol and Hydroxychloroquine (HCQ) and supply to the neighbouring countries have upped medical diplomacy and made India the shining star in tackling the pandemic. This is also one of the reasons for the increase in the share of the pharma industry.

India has been a cradle of inventions throughout its glorious history and this will remain the same in the COVID 19 crisis.  IIT Delhi and Japan's National Institute of Advanced Industrial Science and Technology (AIST) has discovered that an ayurvedic herb Ashwagandha can be an effective therapeutic and preventive drug against the COVID 19 infection.

Corona crisis in Indian Pharma caused a shortage of Active Pharmaceutical Ingredients (APIs) due to dependency on China for their imports. But this has made India to increase their own production and become self-reliant. As the saying goes that “There is light at the end of every tunnel”, every crisis brings its own set of opportunities, COVID-19 is a wake-up call for India and if India plays its part well, we have an opportunity to become the alternate manufacturing location to China and The Pharmacy to the world. 

Miss. Sulaikha Abdul Kareem 3rd Pharm.D

DISEASE X: THE IMPENDING PESTILENCE

PRIORITY EQUITABLE CANDIDATES AND AFFLICTION

1.      Zoonotic viruses

2.      Synthetic viruses/bioweapons

3.      Bacterial infections

4.      Crimean-Congo hemorrhagic fever

5.      Ebola virus disease and Marburg virus disease

6.      Lassa fever

7.      Middle East respiratory syndrome corona virus(MERS-CoV) and Severe Acute Respiratory Syndrome(SARS)

8.      Nipah and henipaviral diseases

9.      Rift valley fever

10.  Zika

11.  “Disease X”(MAJOR PANDEMIC)

Disease X is implicit to be a major outbreak. This is a placeholder name that was adopted by the World Health Organization (WHO) in February 2018 on their shortlist of blueprint priority disease given to the very grave threat that unknown viruses the pretense to human health. Each year the WHO updates the list with guidance from experts in all fields of the scientific study of which pathogens pose the most the threat of causing the next global pandemic.

WHY THIS NAME?

WHO adopted this name to guarantee that their planning was sufficiently flexible to adapt to an unknown pathogen (eg.broader vaccines and manufacturing facilities). Disease X is caused by Pathogen X, an infectious agent that is not currently known to cause human disease, but an etiologic agent of a future outbreak with epidemic or pandemic potential.Director of the National Institute of Allergy  and Infectious Diseases Anthony Fauci stated that the concept of Disease X would encourage WHO projects to focus their research efforts on entire classes of viruses(eg.flaviviruses) instead of just individual strains (Zika virus), thus improving WHO capability to respond to unforeseen strains. In 2020, it was speculated, including among some of the WHO’s own expert advisors, that COVID -19, caused by SARS Co –V-2 Virus strain, Met the necessities to be the first  Disease X.

X SPOTLIGHT ON VIRUSES

It is a big query that why X focus is on viruses and why all these viruses appear new. The theory o “new” is very implicit. The viruses included in the Blueprint list are called emerging because they were identified only recently, after having caused diseases in humans. However, these viruses existed in nature for a very long time, in animal reservoirs. The Nature journal estimated that, if all viruses present on the planet were aligned, they would cover a distance of 100 million light-years. A rough estimation based on a study in bats suggests that at least 3,20,000 viruses can infect mammals and that all species of vertebrates together could host at least 3 million and a half different viruses.

SUMMONS VS ADVANCES IN DRUG DEVELOPMENT

The product development cycle remains lengthy for de novo medical counter measures: diagnostic tests normally take 2-5 yrs to develop and 5-10 years of their completion before procurement can be initiated. The timeline for vaccines development is even longer since it requires human Safety and efficacy data.

Technological opportunities speed up discovery and translation of new products. This lead to the discovery of effective antiviral drugs which extend to papillomavirus, enteroviruses, Hepatitis C virus over the next 5-10 years. Currently,18 specific antiviral drugs (excluding interferon)are licensed in the UK, with more in phase 3 clinical trials or available on expended access. Cloning and sequencing have provided tools to identify viral enzymes and have brought the day of the “designer drug” nearer to reality. At the other end of the spectrum of drug discovery, huge numbers of compounds for screening can now be generated by combinatorial chemistry. The thrust to find drugs effective against HIV has also stimulated research into novel treatments for other virus infections including herpes virus, respiratory infections, and Hepatitis B and C viruses.

Is the apocalypse really upon us? Well maybe…but our greatest good and what we least can spare is hope itself.

Miss. Anitta Thomas, IIIrd B.pharm

COVID-19 IMMUNITY PASSPORT: PRACTICAL AND ETHICAL CHALLENGES

During this pandemic period, one of the controversial concept, that some governments have suggested including Germany, Chile, Italy, the US, the UK is the use of immunity passport –ie, a document that certifies an individual has been infected, recovered and is purportedly immune to SARS-CoV-2 by performing a blood test. Imagine a future where our job and all sorts of normal social activities will be based on blood testing. A positive antibody test and a negative virus test will help the individual to get an immunity pass and will be relaxed from physical restrictions and can return back to normal life. Given that the person is proven immune to the disease and can’t get re-infected and so no potential public health risk. This has been proposed in order to begin reopening of the economy around the world.

Chile become the first country to provide certificates and officials in Italy and Germany are also considering it. In China, “heath code” apps are used to decide the movement of people. India’s own contact tracing app Aarogya Setup is designed to keep track of the users and alert them when they come in contact with COVID-19 patients, but it will not restrict the people’s movement. Obtaining the immunity pass will provide some privilege to the recovered patients, but have a negative impact on the healthy, non-immune people who managed to stay safe and ward-off virus.

Some of the health, experts are debating the idea of giving this passport because this will only work if people really are immune to re-infection. Reports from South Korea and China suggested some recovered patients getting re-infected. Most of the studies show people who recovered develop antibodies to the virus, but some of them have very low levels of neutralizing antibodies in their blood. No evidence suggesting how long the developed immunity last to guarantee future protection.

One of the major issue highlighted by WHO include unsatisfactory results with the available rapid immunodiagnostic tests, which needs further validation to decide their accuracy and reliability. Low specificity cause false-positive results leading people to think they are immune when they aren’t, whereas low sensitivity cause false-negative results in people who have few antibodies. It is needed to differentiate between past infection from SARS-CoV-2 and those caused by the 6 known set of human coronaviruses. Two among them are viruses that cause MERS and SARS. People infected with anyone of these viruses may produce antibodies which will cross-react with antibodies produced in response to SARS-COV-2 infection. Remaining 4 viruses cause the common cold and circulate in the body. Then the volume of testing needed is unfeasible. Two tests per person are minimum required because anyone tested negative might later become infected and needed to be retested to be immune certified.

Another important aspect is to understand the proportion of a population that has been infected with SARS-COV-2. The term Positive Predictive value (PPV) which means “the probability that subjects with a positive screening test truly have the disease” is directly related to the prevalence of the disease in a population. For any given test (ie specificity & sensitivity remain the same) as prevalence decreases, PPV decreases because there will be more false positive for every true positive. So when the prevalence of disease increases, PPV increases because there will be less false-positive cases. This is an important concept. For an immune passport to work, there have to be enough potential passport holders to boost the economy.

Countries with the highest, COVID-19 infections rate may have the best reason to create immunity passport, but the number of recovered patients may not be enough to make the development of this program worthwhile. The WHO estimated that only 2-3% of the global population had recovered from the virus as of April 2020. Though it varies by region, no more than 5% of the population have antibodies (by contrast, around 70% of the population needs to have antibodies either through recovery or vaccination).

Countries like New Zealand, Australia. Taiwan, Vietnam that have successfully flattened the curve –had fewer cases and thus less incentive to initiate immunity passport.

Ethical challenges include monitoring private details which could be people’s travel history, locations and other health information. Marginalized groups (racial, religious and other minority groups) will face more scrutiny. In the US, digital incarceration has already increased. Shortage of testing suggests that the wealthy and powerful are more likely to obtain a test than the poor and vulnerable. Social and financial inequities would be amplified. People will be divided and labelled as immune-privileged and immune-deprived. Employers preferentially hire those having confirmed immunity. There will be a new form of discrimination, when employers, insurance companies and law-officers access private (mental health records and genetic information) details for their own benefit. People who managed to stay at home wilfully seek out infection –putting themselves at risk to get the benefits of passport holders. Sometimes they obtain documents illicitly through bribery, forgery.

There are “vaccination certificates” permissible under the International Health Regulations, which are already accepted by the WHO. They incentivize individuals to obtain vaccination against the virus whereas immunity passport incentivize infection.

Confronting with these challenges, till vaccination, government officials should invest available time, talent and money into areas like a test, trace and isolate. Health and personal data should be anonymised. All policies and practices must be guided by a commitment to social justice.

Miss Maria Thomas 5th Pharm.D

DRUG RE PURPOSING - MAKING MARVELLOUS OUT OF THE EXISTING

Thalidomide was once a well-known drug used for morning sickness in pregnant women,  then withdrawn in 1961 for its teratogenic effects which led to limb defects in more than 80% of children exposed in utero. And again, it regained its position in the market after a couple of years with brand new indications, as a potential remedy for the treatment of leprosy and multiple myeloma - a clear cut evidence of how drug repurposing can breathe in new life to a failed drug.

According to reports, the number of FDA approvals has been declining since 1995 with a success rate of merely 9.6% for the drug development programs from 2006-2015. In this scenario, drug repurposing or reprofiling presents as an efficient, economic and riskless innovation that can bring out promising results. Kudos to the efforts of those brilliant brains for working tirelessly on this drug development strategy, that modifies old drugs for new uses!

The basic idea behind drug repurposing is the fact that common molecular pathways contribute to many different diseases.It is indeed a consequence of the principle of polypharamacology and hence  represents a shift from the single to multiple target paradigm in drug discovery.

 While the conventional de-novo drug discovery process takes about 10-15 years for the translation of a promising molecule to an approved drug, this approach takes only about 1-2 years to identify new drug targets and an average of 8 more years to develop a repositioned drug. It is actually a boon to those with rare and neglected critical illnesses, for whom the big pharma are not willing to work due to low return on investment. Lack of activation barriers, decreased number of clinical trials, which in turn cut down time,cost and labour are the added advantages of this approach. However, lack of expertise in the legal area of drug repositioning, coupled with the complexity of pathways and mechanism of diseases makes this a cumbersome process  in the eyes of atleast a few.

Drug repurposing was sometimes just serendipitous -like those of sildenafil, originally meant for hypertension now being used to treat eretile dyfunction! But the need of the hour is the development of a deliberate systematic approach with a blend of experimental and computational aids to bring out life changing transformations.

DRUG REPURPOSING FOR COVID-A GLOBAL NEED

From the late fall of 2019, we have been witnessing the most devastating pandemic ever known. As of now, the best justified drugs for repurposing to treat covid are the host factor targeted drugs- hydroxychloroquine, azithromycin, camostat, nafamostat and the viral Rdrp targeted drugs-remdesivir and favipiravir. Additionally, phenotypic screening methods based on viral entry and replication are on development to survey more drug candidates.It has in fact become a global emergency that calls for researchers, ethics boards and regulatory bodies to come and work together on this concept to cobat the COVID!! 

Miss Rimisha Thomas IV Pharm.D