India has already become the world capital of diabetes and heart diseases, and is set to acquire the same dubious distinction in other chronic diseases, too. Considering the need for long-term treatment and the higher risks these diseases pose to specific population groups, pharma companies are reworking prevalent treatment methodologies and ushering in innovations
According to a report released by the global non-profit organisation Partnership to Fight Chronic Disease (PFCD) last year, over 20 percent of India’s population is suffering from at least one of the chronic diseases. This is estimated to cost India $6.2 trillion during the period 2012-2030. The report also mentions that four non-communicable diseases—cancer, heart ailments, respiratory diseases and diabetes—are most likely to cause death during the most productive years.
According to Anil Khanna, Partner, Wisdomsmith Advisors, “The total Indian market size for chronic diseases is over Rs 45,000 crores and is growing significantly. The key categories are cardiac, anti-diabetic and neuro valued at Rs 14369 crores, Rs 10568 crores and Rs 7072 crores, respectively. Other therapies, which have a large component of chronic medicines are respiratory (Rs 8579 crores), pain (Rs 7886 crores), gynaecological (Rs 5909 crores) and blood-related disease (Rs 1438 crores).”
Most chronic diseases need a long period of treatment making patient compliance a big challenge in India. However, the industry is addressing the issues of disease duration, disease intensity, number of complications, degree of disability and management of symptoms through new drug delivery systems.
Vinod Kumar Arora, Principal Advisor, Institute of Good Manufacturing Practices India observes, “Drug delivery systems address treatment-related factors, frequency of dosage, and the cost and complexity of treatment. The last decade has seen substantial accretion in industry valuation from adoption of biologics for the control of diabetes, inflammation and cancer. In the long term, we expect substantial growth in nucleic acid drugs built through approaches like microRNA, RNAi, direct mRNA, gene therapy and gene editing.”
Addressing the patient compliance issue from a pharma company’s perspective, Dr Sanjit Singh Lamba, MD, Eisai Pharmaceuticals says, “Patient adherence is very critical, and we do understand the reasons for non-adherence. In our experience, some of the crucial reasons include lack of efficacy, high cost, complexity of administration, difficult accessibility, etc.”
Highlighting the importance and relevance of innovative drug delivery methods in the chronic disease arena, SV Veerramani, Founder and Chairman, Fourrts India, says, “Innovative drug delivery systems can certainly help in adherence to dosages and also availability of the drug in the body at the right site and right time. This will certainly help treat the chronic disease better.”
“However,” he continues, “the other challenges in patient adherence are in the areas of dosage compliance and prevention of the missing of a dose. Sometimes, a tablet or capsule is preferred over dry granules, sachets or liquids. Hence, we tend to introduce the more tablet and capsule dosage forms.”
Dr Damodar Bachani, Ex-Deputy Commissioner (NCD), Ministry of Health & Family Welfare, Government of India, has another view. “People’s perception about chronic diseases needs to be changed. Firstly, non-communicable diseases (NCDs) may not display any symptom for a long period of time. In general, people perceive disease as appearance of symptoms. This may not be true for many NCDs as these are silent diseases to begin with. That is the reason many persons do not even start the treatment prescribed for them.”
So, why do people ignore a chronic disease until it becomes severe? Dr Bachani answers, “The tendency to stop or reduce the frequency of medication as soon as one perceives relief and a feeling of improvement can stretch the duration of treatment. Therefore, at every point of contact (doctor, nurse and pharmacist) patients and their caretakers must be counselled that reduction or stoppage of prescribed treatment could lead to complications requiring very costly treatment or hospitalisation. Many people opt for alternative medicines (like herbal preparations containing heavy metals), which may worsen the situation.”
Talking about the work being done by his company, Dr Lamba points out, “Our objective is to ensure that the patients, who begin therapy with our drugs, continue to remain on the therapy for the required duration and complete the dosing regimen for a better outcome, resulting in improved quality of life. For example, we have developed oral disintegrating strips of mecobalamin called Quicobal because it is very difficult for oncology patients to take injections and tablets on a continuous basis.”
According to WHO’s report, premature deaths caused by NCDs have risen due to multiple health transitions like demographic change in population, nutritional change with high calorie food consumption and low physical activity levels, etc. NCDs are the leading cause of death accounting for 60 percent of all deaths in India. From 1990 to 2016, the largest disease burden or disability-adjusted life year (DALY) rate increase was observed for diabetes at 80 percent followed by ischaemic heart disease at 34 percent.
In 2016, three of the five leading causes of disease burden in India were non-communicable, with ischaemic heart disease and chronic obstructive pulmonary disease (COPD) as the top two and stroke as the fifth leading cause. The DALY rate across India in 2016 was nine-fold for ischaemic heart disease, six-fold for stroke and four-fold each for COPD and diabetes.
According to Dr Bachani, “While ischaemic heart disease and diabetes generally had higher DALY rates in states that are at a more advanced epidemiological transition stage toward non-communicable diseases, the DALY rates of COPD were generally higher in the EAG states that are at a relatively less advanced epidemiological transition stage. On the other hand, the DALY rates of stroke varied across the states without any consistent pattern in relation to the stage of epidemiological transition.”
DALY rates of chronic disease are increasing significantly, so will bringing innovation in drug delivery systems help in cutting down the incidence? Dr Singh responds, “Innovation in drug delivery may not necessarily bring down the incidence. However, it can definitely improve compliance leading to improved outcomes and quality of life.”
Accessibility and affordability
With changing lifestyles, chronic diseases are on the rise and becoming a major health concern in India. Earlier, people took this to be more of an urban lifestyle-related disorder. However, it has already reached rural areas.
With 70 percent of India’s population living in rural areas and most of them preferring public health centres, do they have adequate access to medicines for chronic diseases?
Dr Bachani is sceptical. “Medicines for chronic diseases are not prescribed in many rural areas as there is no qualified doctor.”
He goes on to suggest a solution. “We could explore a more decentralised system of dispensing medicines close to the homes in villages through auxiliary nurse midwives (ANM) at the sub-centre or accredited social health activists (ASHA) may be explored. Patients are dispensed medicines for a maximum of one month and they have to travel long distances to come for a refill. Even though the drugs are free, they lose money on travel and lost wages. This is also a reason for poor drug adherence. Prescribing generic medicines or dispensing through co-operative drug stores at a reasonable cost can help to reduce out-of-pocket (OOP) payments.”
Unlike developed countries, in India patients bear their own medical expenses. Now, the government is working aggressively towards making medicines affordable to everyone. Several steps have been taken to bring essential medicines under the National Health Mission.
Dr Bachani says, “The objective is to reduce OOP expenditure in chronic disease management. And the government has already initiated steps like dispensing medicines at reasonable cost through Jan Aushadhi Kendras, prescription of quality generic medicines at low cost, capping prices of essential medicines and deployment of e-procurement and logistics management systems for regular assessment of supply and demand.”
Along with the government, pharma companies too have initiated several programmes towards making medicines for chronic disease more affordable.
Single dosing effect
For cancer and diseases of the central nervous system, Eisai India has a tiered pricing programme for patients. Dr Singh explains, “In our country, affordability still remains a key challenge for most of the patients. As a company, in therapeutic areas where medical needs are unmet, we believe in launching original research products with high potency. This offers the patients once-daily dosing thereby reducing the pill burden and ensuring adherence. At Eisai, based on an innovative tiered pricing model which we run for Halaven, Lenvima and Zonegran, we ensure that the treatment is tailored and customised on the basis of the patient’s capacity to complete the therapy.”
However, such programmes will help only a limited number of patients. In order to benefit a larger number of patients, companies will need to address both cost and dose. Dr Singh suggests, “Over a period of time, we have seen that once-a-day dosing can reduce infusion time and improve the patient compliance and yield better outcomes.”
While explaining the benefits of a single dose, he adds, “Where patients need to be admitted to hospitals for administration of anti-cancer medications, our drug (Halaven) can be given in a matter of four to five minutes, thereby reducing longer waits at hospitals. This results in reduced economic burden and improves the overall experience of the patient.”
Veerramani also agrees with the idea of single dosing. “Normally once-a-day dosages are more convenient to patients. So, we are striving to work on sustained release formulations, which can be efficacious for 24 hours.”
Arora, too, emphasises, “Innovations in dosage forms and dose delivery systems across a wide range of medications offer substantial clinical advantages. These include reduced dosing frequency, improved patient adherence, minimum fluctuation of drug concentrations, maintenance of blood levels within a desired range, localised drug delivery; and the potential for reduced adverse effects and increased safety.”
Addressing the issue of innovation-driven cost, Arora says, “The advent of new large-molecule drugs for previously untreatable or partially-treatable diseases is stimulating the development of suitable delivery systems for these agents. Although advanced formulations may be more expensive than conventional dosage forms, they often have a more favourable pharmacology profile and can be cost-effective. Inclusion of these drug dosage forms may help patients remain on therapy and reduce the burden of care.”
Will cost affect innovation?
Chronic diseases drain the patients not only physically but also mentally and financially. The objective of bringing innovation in drug delivery systems is to ensure that the patients who commence a drug therapy for chronic disease, continue to remain on the therapy for a longer duration and complete the dosing regimen for better outcomes resulting in improved quality of life. For improving existing dosage forms, pharma companies need to invest heavily in research. Pointing out the cost aspect, Khanna alerts, “Innovation in drug delivery system can help only if it improves the ease of taking medicine, there is no higher cost implication, or the cost is less, and there are no side effects.”
Talking about the steps taken by Eisai India, Dr Singh shares, “One of our products, Aricep M, intended for elderly patients suffering from dementia has been re-developed by our team to make the tablet size smaller to make it easier to swallow, thus ensuring better compliance. Thus, a reduction in tablet size help in increasing patient compliance.”
In chronic diseases, initially patients are very serious about the disease and diligently comply with the medications prescribed. However, over a period of time, compliance drops. This is where the need for once-a-day dosing arises. Dr Singh adds, “Our epilepsy medicine where compliance is related to the number of the pills that a patient needs to take, we have been providing once-a-day dosing advantage to the patients.”
In chronic disease, over a period of time, there is an increase in disability and the patient becomes more and more dependent on the family member or the caretaker. In such cases, it is important to educate the caregiver.
Singh informs about Eisai India’s initiatives in educating the caregivers, “We work very closely with the caregivers and family members and educate them so that they can impress upon the patients the need to comply with daily medicines for effective outcomes.”
Arora sums up, “Understanding the dynamics of drug delivery design, pharmacokinetics, and the clinical effects would require cross-discipline collaboration. The industry will need to work academia, regulatory agencies, patient advocacy organisations and other stakeholders. However, the future of drug delivery is more exciting than ever. Continuing advances in understanding of traditional and modern delivery systems and emerging technology are expected to provide greater clinical improvement in all therapeutic areas. Not so long ago, cell therapy was viewed as having little to do with the pharma industry. Today, attitudes have changed substantially.”