Nobody’’s children

As per the 2011 census, India has around 158 million children in the age-group 0-6 years, with 20 states and union territories accounting for over one million children in this age group. This age group makes up approximately 13 per cent of the total population of the country, and while there has been a slight decrease in the last decade, India is nowhere near developed nations like the US where the proportion of children has shrunk and is predicted to shrink faster over the coming decades. India thus represented a booming market for companies targeting this age group.

Shrinking or not, the younger age group represents the future of any country and indeed this planet but in terms of medicines, this demographic has been ignored. Shashank Sandu, Managing Director, Sandu Pharmaceuticals reveals the facts, “Globally nearly nine million children under five years of age die every year, with pneumonia, diarrhoea, and neonatal causes being the major killers.”

Hitesh Gajaria, Partner, KPMG presents the current Indian prescription-based paediatric drugs market and says, “In the Indian context the market share of paediatric drugs is a relatively minor portion of the pharma pie (less than10 per cent). While a few companies have specialised product portfolios for child care, most big players manufacture few or no drugs specifically for this demographic.”

There is no doubt that the potential exists. For instance, globally, the paediatric drugs and vaccines market is growing at a rate of four to six per cent annually and is estimated to reach $85 billion by 2017.

“Almost all the paediatric drugs are originally developed for adults (barring few vaccines) and the results are extrapolated to children or often used as off label. This strategy makes safety a major concern for medicines for paediatric use as children are not small adults.” Dr Ajit Dangi President & CEO, Danssen Consulting

The US represents the largest market for paediatric drugs and vaccines while the EU follows. Dr Ajit Dangi, President and Chief Executive Officer, Danssen Consulting informs, “The most over prescribed drug for children globally, Novartis’ brand Ritalin (methylphenidate HCl) is prescribed for Attention Deficit Hyperactivity Disorder (ADHD ) and 90 per cent of global sales come from the US. It is estimated that 11 per cent school going children in the US are diagnosed as suffering from ADHD. The total US sales of methylphenidate crossed $1.4 billion in 2012.”

It is projected that future growth in the paediatric drugs market is likely to be driven by the Asia-Pacific markets where the market is estimated to grow at a compound annual growth rate (CAGR) of 11 per cent.

In India, the paediatric drug market is being tapped by both multinational as well as domestic pharmaceutical players. Multinational pharma companies like Pfizer, Johnson & Johnson (J&J), Allergen Abbott Laboratories, Sanofi-Aventis, GlaxoSmithKline, Merck, Merck Serono, Novartis, Novo Nordisk, Allergan, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Nestle, F Hoffmann-La Roche, and UCB Pharma have a presence in India and among Indian companies Lupin, Dr Reddy’s Laboratories and Cipla are the largest players with allopathy drug portfolios for the paediatric population.

Historically speaking, India does not have a tradition of allopathic drugs. Physicians following the traditional medicinal sytem, called vaidyas, were the main source of treatment. As time passed, society’s needs changed and the allure of quick relief made people switch to allopathic drugs.

However, old habits die hard and parents still prefer to opt for traditional medicines especially when their children are concerned as they are perceived to be safer and without severe side effects. A handful companies like Sandu Pharmaceuticals, Himalaya, Dabur and Baidyanath have captured this market with varied range of paediatric herbal formulations. Feeding into this perception Sandu informs, “Considering the safety aspects, herbal drugs and nutritional supplements are well-accepted in children, one of the most sensitive population in the clinical set-up.”

“Today, we cannot ignore the fact that promotion of appropriate and safe drugs in children is the global need of the hour.” Shashank Sandu Managing Director Sandu Pharmaceuticals

To some extent, this reasoning was justified as most medicines had not been tested on children during clinical trials. Clinical practitioners resorted to the practice of reducing the dose of the adult medicine based on the body weight and age of each child patient.

Referring to this reality, Sandu says, “Over the past few decades, experts in clinical research were of the view that we must protect children from research. Now there is a gradual shift in the focus that we must protect children through research. Global market for paediatric hormones is forecast to grow at a CAGR of seven per cent.”

Wide therapeutic area

Among many categories of paediatric medicines, respiratory, anti-infectives, central nervous system (CNS), dermatologicals, anti-diarrhoeals as well as vaccines have a large share. J&J is one of the few MNCs which has developed a slew of over dozen preparations for children under an umbrella brand.

Giving details, Dangi says, “TYLENOL has basic ingredient acetaminophen (paracetamol) ) with combination with other safer drugs for ailments like cold and cough, fever, allergy, pain and aches, flue etc. This is one of the most successful paediatric franchises in the US; although of late it has received flak from the US FDA for several quality issues resulting in many product recalls.”

Since children cannot swallow solid dosage forms like tablets and capsules, most oral paediatric preparations have to be developed as oral liquids or dry syrups. Simultaneously if a particular medicine has a discernible smell and or unpleasant taste, they are less likely to be accepted. If it falls in delivering substantial relief as well, then children will strictly refuse to take medicines.

Dangi cautions, “This poses a challenge as most drugs are bitter or salty in taste and unless their taste is masked and the preparation made palatable, patient acceptance and therefore compliance becomes a problem. Illustrating with an example, he continues, “Metronidazole which is an anti-amoebic, has an extremely bitter and metallic taste and hence to develop it into a paediatric oral dosage form the salt has to be converted in to an ester, metronidazole benzoate, which is bland in taste and hence can be given a flavour of choice.”

The key therapeutic areas for paediatric drugs in India are gastrointestinal (GI) disorders, HIV, metabolic disorders, asthma, anti-pyretics, nutritional supplements etc. In India, Cipla has a range of approximately 90 paediatric products in different formulations/ dosage forms. It has also developed Deferiprone, the world’s first oral iron chelator and Deferasirox for thalassemic patients. For paediatric HIV, it has developed a triple drug combination (Nevirapine + Stavudine + Lamivudine) in dispersible form. Lupin also has strong portfolio in diabetology, dermatology, and asthma.

Gajaria feels, “Growth in the segment is largely expected from therapeutic segments like – paediatric vaccines and hormone therapy drugs as well as from respiratory and allergy drugs, CNS drugs, and anti- infectives. Although anti-infectives constitute a larger portion of the paediatric market share. The domain has been widely researched and contraindications / reactions are well documented. Newer areas such as paediatric hormones and CNS drugs for use in children are relatively under-researched presently. It is therefore important that information on drugs therapies and reactions and in these segments are well studied and documented.”

Along with the above mentioned therapeutic areas, in-depth research could uncover more areas of unmet medical need in this demographic which could be tapped by Indian pharma companies. “Dehydration, calcium deficiency, worms and malnutrition are the areas of concern,” informs Sandu.

Thrust drives growth

A drug before it reaches to the market takes a long time to pass through the research and development centre and through various regulations. There is a lot of research going on globally on adults but there is limited research being carried out in the paediatric arena. Dangi highlights, “Almost all the paediatric drugs are originally developed for adults (barring few vaccines) and the results are extrapolated to children or often used as off label. This strategy makes safety a major concern for medicines for paediatric use as children are not small adults.”

While informing about the total conducted clinical trials in India, Gajaria outlines, “A study carried out to gauge the number of trials carried out between 2006 -2011 revealed that while 60 per cent of the diseases for which drugs were tested could be attributed to children, only 12 per cent of the trials conducted were in fact for paediatric drugs.”

Dangi explains, “For instance, Aspirin which is in use for over a century as a pain killer needs to be used for children with extreme caution as it causes Reys Syndrome (swelling in the lever and brain ) and hence is contraindicated. However, such conversions can often cause bioavailability and stability problems in some cases. Development of paediatric dosage forms, therefore, is a significant R&D challenge.”

In December 2007, World Health Organization (WHO) published its first ever model list of essential medicine list for children with more than 200 medicines, including HIV/AIDS treatment, vaccines, anaesthetics, hormones, vitamins, and minerals. “This serves as a reference for countries to develop national essential medicines lists, according to their specific public health needs. Indian Academy of Paediatrics (IAP) Drug Formulary is one of the three exclusive paediatric drug formularies in the world. The array of medicines cover mostly the paediatric diseases related with skeletal system, CNS, immunity, respiratory system, endocrine system, skin, infectious diseases and growth milestones. there is still a long way to go in terms of safety and efficacy,” emphasises Sandu.

Pointing out about the clinical trials adverse drug reactions and its data availability, Dr R B Smarta, Managing Director, Interlink Marketing Consultancy comments, “There is no sufficient data available on an adverse drug reaction across the globe. The emerging markets are likely to require paediatric drugs and vaccines in various therapeutic areas. With growing demands medical practitioners need to be well versed with the knowledge of prescribed dosages. This will be only possible if practitioner looks at the pharmacokinetics and pharmacodynamics and prescribes the right dosage.”

Gajaria notes on why there is less research being carried in the paediatric segment saying, “This could be attributed to the fact that there are controversies surrounding paediatric trials from ethics and regulatory points of view. Paediatric trials also face logistical issues from a patient recruitment viewpoint. Moreover, paediatric trials rely heavily on funding provided by the government or other non-profit organisations dedicated to child care. This is not the case in adult trials which receive most of their funding from industry players.”

Sandu briefs, “For several years, physicians were paralysed with lack of information and options for prescribing treatment to patients in the paediatrics market. Many were compelled to rely on off-label prescription of drugs, as the market was deprived of approved drugs in many segments. This also created worry among physicians and paediatricians pertaining to the safety and efficacy of these drugs. We, being firmly footed in ayurvedic medicines for over a century, have focused our paediatric range.”

Regulations

The IAP Drug Formulary contains IAP recommendations for 555 paediatric illnesses contributed by respective sub speciality chapters of IAP, 613 monographs of drugs used exclusively in paediatric therapeutics and details of 1099 brand names of drugs available in India. Several regulations such as Best Pharmaceuticals for Children Act (BPCA), Paediatric Drug Research Equity Act (PREA), Food & Drug Administration Modernisation Act (FDAMA), have been enacted to standardise and streamline the paediatric drugs market. Bodies like the FDA and EMA have adopted new regulations that encourage and incentivise companies to carry out paediatric trials. Sandu shows concern, “Today, we cannot ignore the fact that promotion of appropriate and safe drugs in children is the global need of the hour.”

Gajaria highlights, “The International Conference on Harmonisation (ICH) Guideline of the ICH distinguishes between five developmental stages: pre-term newborn infants, term newborn infants, infants and toddlers, children, and adolescents. Such errors could result in drug toxicity in children and may also cause many adverse drug reactions like allergies. Using children to test drugs that are not formally approved comes with its own share of ethical issues. Moreover, since the protocol behind paediatrics trials is not standardised in most countries, these trials carry inherent risks. ”

Sandu informs about precautionary measures which need to be taken in order to promote clinical trials in children segment, “All countries should establish national and regional monitoring systems for the detection of serious adverse reactions to medicines in children. When such reporting systems exist, it is crucial that manufacturers follow up on adverse reactions to their products once they are on the market.”

Compared to allopathy drugs, herbal medicines are perceived to result in less side effects and to be safer for paediatric clinical trials. Sandu opines, “Our experience is that it is comparatively easier to enrol paediatric patients in a trial of herbal medicines as the parents themselves believe that herbal drugs are safe and I think they are right to a certain extent.”

Government programmes and initiatives

WHO in December 2007 launched a campaign called “Make medicines child size” which raised awareness and stimulated action to improve the availability of safe, effective, and quality medicines for children. Sandu emphasises, “Safety should be of the topmost priority while treating our children.”

Smarta mentions, “Every country has a different set of concerns. The Government of India should develop a prioritised list of diseases for children and take long-term projects. These projects can run over a period of three to five years with public and private partnerships where sufficient amount and resources are spent in drug discovery, clinical trials and new solutions which can be later brought to the world.”

Realising the fact Dangi informs, “Given the fact that IAP ,an official body of paediatricians has just about 20,000 members shows the dearth of professionals in this important medical field.”

He however praises the efforts being taken by the Indian government saying, “In spite of these challenges, there is one success story and that is total eradication of polio from Indian soil due to abundant availability of affordable oral polio vaccine and excellent communication strategy using celebrities like Amitabh Bachchan to spread the message nationwide using electronic media. It is hoped that the Ministry of Health emulates some of the strategies of WHO and US FDA to stimulate growth of paediatric medicines in India and replicates its success as is done in eradicating polio. After all a healthy child is the future of India.”

Children are considered gifts of God and giving them a healthy life becomes the utmost wish and duty of every parent. After a long campaign driven by the research efforts of pharma companies as well as the Government’s initiatives, we managed to eradicate polio from the country completely and India became a polio free nation.

Overcoming a single disease will not suffice the need as there are many areas which need equal interest from pharma companies as well as the Government. We the people will have to encourage them to work on the so far neglected category of childhood diseases.

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