India’s attempt to regulate increasing inflow of foreign direct investments into the pharmaceutical sector

India’s attempt to regulate increasing inflow of foreign direct investments into the pharmaceutical sector does not seem to yield the desired result as yet. Although government allows 100 per cent FDI in pharma sector through automatic approval route in new projects and investments in the existing companies only through the Foreign Investment Promotion Board approval, there has been a steady rise in the number of acquisitions of large Indian pharmaceutical companies over the last ten years. The first major acquisition in pharma sector was in 2008 when the Japanese giant, Daiichi Sankyo, took control of India’s largest pharma company, Ranbaxy Labs for $4.6 billion. Another major acquisition was of Shantha Biotechnics by the French pharma company Sanofi-Aventis. And the most recent FDI investment was for acquiring Indian generic drugs company, Agila Specialties, by the US based MNC Mylan Inc for a sum of Rs. 5,168 crore. The government had cleared this deal a couple of months ago. Now, Sanofi is understood to be planning to acquire a medium size company, Elder Pharmaceuticals. FDI in the pharma sector has more than doubled to $1.07 billion during April-August period of this year as against an FDI of  $487 million during April-August 2012, as per the latest data of the Department of Industrial Policy and Promotion. Over 96 per cent of the total FDI in the sector between April 2012 and April 2013 has come into brownfield pharma projects. The situation is scary as MNCs already control 35 per cent of the domestic pharmaceutical business.

The very objective FDI policy in this sector should be to bring some check on unrestricted takeovers of Indian companies by MNCs. India’s huge domestic market with no price control on patented products and availability of cheap manufacturing facilities is a great attraction to MNCs. Public interest groups and patient organizations have been expressing serious concerns over this dangerous trend as MNCs usually start launching highly expensive patented drugs after the acquisitions. Introduction of product patent regime in 2005 helped the MNCs to import large number of patented products for marketing in the domestic market. This trend is continuing and these drugs are being sold at exorbitant prices as the National Pharmaceutical Pricing Authority did not try to bring them under price control as yet. Most of the patented drugs are highly expensive on account of excessive profiteering, loading of huge trade commission and promotional costs. It is in view of this trend, the commerce & industry ministry is proposing to further tighten the flow of FDI in the sector by incorporating some major changes in the policy including conditions like a cap of 49 per cent on brownfield projects and mandatory investments in R&D by the acquiring company. The provision of mandatory investments in R&D may not be of much help to curb this trend as the MNCs would readily agree to that condition. It is not that easy to track how genuine is the drug research in India and actual costs incurred  by pharma companies. It is rather unfortunate that divergent views on the issue by various Central ministries and departments are holding up taking such a critical decision.

CHMP recommends marketing authorisation for GSK's cervical cancer vaccine Cervarix

The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorisation for a two-dose schedule in 9-14 years old girls for GlaxoSmithKline's cervical cancer vaccine, Cervarix [Human papillomavirus bivalent (types 16 and 18) vaccine, recombinant].

“We are delighted by the positive opinion issued by CHMP on a two-dose schedule for Cervarix. It represents another major milestone in our commitment to reducing the global burden of cervical cancer which remains high. Many countries are unable to implement national immunisation programmes in young adults with high coverage. A two-dose vaccine schedule has the potential to be easier to deliver than a three-dose schedule, thereby expanding the population that could benefit from protection.” said Thomas Breuer, senior vice president and lead physician, GSK Vaccines.

The EU licence application is based on the results of a phase III study (HPV-070) which showed that two doses of the vaccine in girls aged nine to fourteen years provide an immunogenicity matching the currently licensed three-dose schedule in fifteen to twenty five year olds.

A CHMP positive opinion is one of the final steps before marketing authorisation is granted by the European Commission, but does not always result in marketing authorisation.

The vaccine is currently approved in the EU for use in females from the age of nine years, administered according to a three-dose schedule (vaccination at months 0,1 and 6) for the prevention of premalignant genital (cervical, vulvar and vaginal) lesions and cervical cancer causally related to certain oncogenic Human Papillomavirus (HPV) types. The two-dose schedule will only apply to vaccination of girls aged nine-14. The three-dose schedule remains recommended for girls and women aged 15 years and above.

Cervarix is also approved in the US.

GSK Vaccines is active in vaccine research and development and has 13 manufacturing sites strategically positioned around the globe. Of the 883 million doses of our vaccines we distributed in 2012, over 80 per cent went to developing countries, which include the least developed, low- and middle-income countries.

GSK is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

KKR to invest $200m in India pharma group Gland

KKR, the private equity firm, said it would spend $200m on a minority stake in an Indian maker of generic drugs for the US market, in the latest in a series of acquisitions by foreign investors into the export-oriented pharmaceutical industry in India.

Hyderabad-based Gland Pharma produces anticoagulants – used in dialysis or heart bypass surgery to prevent blood clotting – anaesthetics and other injectable medicines from five different manufacturing facilities in the southern state of Andhra Pradesh.

In the past few years, several large Indian generic drug companies have been acquired by global players, including Daiichi Sankyo, Sanofi, and Abbott Laboratories.The privately-held company, which was founded by Indian chemist PVN Raju in 1978, is in the process of building a large-scale facility that will nearly double its capacity, allowing it to expand both its overseas and domestic sales.

India’s large generic pharmaceutical industry – which developed in the context of a weak patent regime that allowed Indian companies to copy drugs that were protected elsewhere – has been drawing interest from international drug companies looking to secure generic supplies for western markets.

Most recently Mylan, the US-based generic maker, was given the regulatory go ahead for the $1.6bn acquisition of Agila Specialties, the Indian vaccine and injectables producer.

But India’s Congress party-led government has become anxious about the growing foreign control of India’s drug producers, which they believe could lead to companies staunching domestic sales and instead turning their production to more lucrative overseas markets.

The government is now considering new restrictions on foreign takeovers of Indian drugmakers to prevent supply shortages in the domestic market.

Approval for Mylan’s takeover of Agila Specialties was delayed for months, but India’s need for foreign currency to bridge its current account deficit appeared to tip the balance in favour of the transaction. However, the debate on new restrictions is still active within the government.

Dr Penmetsa said he did not believe that KKR’s acquisition in Gland would face any major regulatory difficulties from Indian authorities.

Gland, which will remain majority Indian owned, did not reveal the size of KKR’s stake, although it may be increased later if KKR buys out another shareholder.

Ravi Penmetsa, the company’s vice-chairman and managing director, said that Gland Pharma exported roughly 70 per cent of its production, but that it would continue to sell in India after its expansion, in spite of receiving higher margins overseas.

In its most recent results, Gland reported revenues of more than $200m and earnings before interest, depreciation, taxes and amortisation of $58m.

“We are committed to the Indian market – it is our home market,” he said. “Why would we stop supplying our family and friends?”

With its investment, KKR is buying a stake in the company previously held by Evolvence India Life Sciences, a fund operated by an India and Middle East-focused private equity player. But KKR is also injecting fresh capital that will help finance construction of Gland’s new manufacturing facility.

KKR’s investment in Gland, the largest by a private equity company into India’s drugmakers, comes at a time when many foreign financial investors are debating whether the Indian economy has bottomed out.

Gland is KKR’s seventh private equity investment in India, bringing the total value of the portfolio to $1.4bn. The deal is being financed out of the firm’s new $6bn fund.

World AIDS Day 2013 – Revised guidance to facilitate development of new medicines

The European Medicines Agency plays a key role in the authorisation of medicines to treat human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). All antiretroviral medicines in the European Union (EU) have to be authorised centrally at European level, rather than in each Member State separately. This aims to allow the rapid availability of the medicines across the EU.

There are approximately 34 million people living with HIV globally. Over the past few years, the authorisation and availability of new, potent antiretroviral agents has changed the landscape of HIV treatment. With these new medicines, most patients are now able to achieve sustained viral suppression. Viral resistance has also become less frequent.

However, new antiretroviral agents are still needed for patients infected with virus that shows extensive resistance to existing therapies or who cannot tolerate certain agents, or combinations of agents, to which their virus remains susceptible.

In its draft revised guideline on the clinical development of medicines for the treatment HIV infection, the Agency sets out development strategies to facilitate the development of such agents.

The document provides a new definition of populations included in clinical trials, moving away from a focus on treatment history (distinguishing between treatment-naïve and treatment-experienced patients) to an emphasis on documented viral resistance. Guidance is provided on the development programmes and the type of data that should be provided for new antiretroviral agents. The draft guideline was released for a six-month public consultation in September 2013.

Over the past year, the Agency’s Committee for Medicinal Products for Human Use(CHMP) recommended granting marketing authorisation for four new therapies for HIV‑1 infection (Tivicay, Vitekta, Tybost, Stribild).

So far, a total of 34 anti-HIV medicines have been authorised in the EU on the recommendation of the Agency. The Agency has also recommended the authorisation of medicines used to treat infections and cancers in patients with AIDS.

In addition, the Agency has given opinions on three anti-HIV medicines for use exclusively in markets outside the EU. These opinions are given in cooperation with the World Health Organization (WHO) for diseases of major public-health interest.

More on World AIDS Day

World AIDS Day is held on 1 December each year and is an opportunity for people worldwide to unite in the fight against HIV, show their support for people living with HIV and commemorate people who have died. World AIDS Day was the first ever global health day and was first held in 1988.

Early dialogue between regulators and health technology assessment bodies key to medicines development

EMA and multiple stakeholders to develop tools for industry

“A strong interaction between regulators and health technology assessment bodies(HTAs) is critical to enable innovation to reach patients, and ultimately for the benefit of public health,” said Guido Rasi, Executive Director of the European Medicines Agency (EMA) at the EMA-HTA workshop on parallel scientific advice which took place on Tuesday, 26 November. “This is the first workshop where we have tried to bridge these two worlds together to share views,” Rasi added.

Some new medicines authorised by the European Commission based on the EMA’s scientific opinions fail to be reimbursed and/or used as expected because they fail to match the requirements of HTA bodies. There is a clear need to initiate early dialogue between medicines developers, the EMA and HTA bodies to discuss and agree on a development plan that generates data that both parties can use to determine a medicine's benefit-risk balance and value.

Since 2010, the EMA has put in place a pilot project of parallel scientific advice with HTA bodies that allows developers to receive simultaneous feedback from both regulators and HTA bodies on their development plans for new medicines. The EMA, with the support of the European medicines regulatory network, has so far conducted 25 parallel scientific advice procedures with several HTA bodies taking part in this pilot project. Currently, a further six procedures are expected to start in 2014.

Following the workshop, and based on the experience gained by all stakeholders, guidance for EMA-HTA parallel scientific advice will be developed and published for public consultation in early 2014. The guidance will detail the timelines and actions whereby applicants can seek simultaneous feedback from regulators and HTA bodies on their development plans. The final guidance will take into account feedback from all stakeholders.

“I believe that this guidance can be a major tool for medicines development, which will help new medicines with a positive benefit-risk balance and expected added value to reach patients in a faster and more transparent way. This simultaneous feedback will ultimately lead to better advice for companies, to help them meet the requirements of all stakeholders and consequently increase predictability,” said Tomas Salmonson, Chair of the Agency’s Committee for Medicinal Products for Human Use (CHMP). This was also discussed by health ministries involved in the HTA Network established under Directive 2011/24/EU.

In addition, HTA bodies have initiated the Shaping European Early Dialogues for health technologies (SEED) consortium, financed by the European Commission, to explore a number of scenarios for conducting early dialogues. The EMA is associated with the consortium and will take part in the dialogues.

The workshop brought together over 280 representatives from the European Commission, European regulators, HTA bodies from 12 European Union countries, EUnetHTA, the pharmaceutical industry, payers, patients, healthcare professionals and academics, as well as representatives from the CHMP, the Pharmacovigilance Risk Assessment Committee, the Paediatric Committee, the Committee for Advanced Therapies, the Committee for Orphan Medicinal Products and the Agency’s Scientific Advice Working Party.

A report and video from the workshop will be published in early 2014.

Notes

• HTA bodies provide recommendations on the medicines that can be paid for or reimbursed by the health care system in a particular Member State.
• SEED is a consortium led by the Haute Autorité de Santé (HAS) in France consisting of 14 national and regional HTA bodies: AETSA (Spain), AIFA (Italy), ASSR (Italy), AVALIA-T (Spain), CVZ (Netherlands), G-BA (Germany), GYEMSZI (Hungary), HAS (France), HIQA (Ireland), HVB (Austria), IQWIG (Germany), ISCIII (Spain), KCE (Belgium) and NICE (UK).

Big Pharma bets its future on a swelling pipeline of biologics

Driven by fears of the patent cliff and lured by the blockbuster prospects presented by new biologics technologies, Big Pharma has become Big Biotech. As of last year, biotech products accounted for 71% of the revenue generated by the top 10 products, according to a new report from the Tufts Center for the Study of Drug Development.

During the past 11 years, reports Tufts, the biotech pipeline has swelled 155%, up from 355 treatments in 2001 to 907 in 2012. Big Pharma is engaged on 40% of those products, helping push the biotech R&D budget from $10.5 billion to $103 billion last year. And product sales for biotech therapies jumped 353%, to $163 billion.

"The notion that large pharmaceutical companies primarily develop small molecule drugs no longer holds," said Ken Kaitin, who helms the center.

Most industry insiders likely gave up that notion years ago. With an extended protection period for biologics, Big Pharma recognized long ago that its future revolved around a more powerful generation of biologics. Analysts have tracked a higher success rate for biologics as well, with new antibody technology getting firmly entrenched in the industry. And second-gen technology platforms promise to keep driving the industry toward biologics as the dividing line between Big Pharma and Big Biotech becomes increasingly blurred.  

Off-Patent Biologics to Boost the Growth of Biosimilars Global Market to Reach US$19.4bn by 2018

Several of the leading 25 manufacturers of biosimilars have been entrenched in the market, and have the experience of marketing products for the last 5-10 years. On the other hand, several companies' position is expected to be challenged over the next ten years, since the rapid growth forecast for the biosimilars market has attracted several new companies to enter this lucrative arena. Current leaders, in order to maintain market share, need to introduce new biosimilars over the next few years with a specific focus on the products in demand. Licensing deals are expected to expand the pipelines of established players, as well as new market entrants.

The global biosimilar market, estimated at US$2 billion in 2012 and expected to touch US$2.7 billion in 2013, is further projected to reach US$19.4 billion by 2018, exhibiting a CAGR of 36.6% over 2009-2018. This growth can be attributed to some of the top-selling biologics coming off-patent over the coming few years and biosimilar manufacturers are bound to make a beeline towards this lucrative opportunity.

Publication Overview

This report reviews, analyzes and projects the biosimilars market for global and regional markets including the United States, Europe, Asia-Pacific and Rest of World. The market numbers illustrated in this report only represent the market exclusively for the product segments and application areas enunciated above. The regional markets further analyzed for 8 more independent countries across Europe - France, Germany, Italy, Spain, the United Kingdom and Rest of Europe; Asia-Pacific - China, India, South Korea and Rest of Asia-Pacific.

The market for application areas of biosimilars analyzed in this study includes Blood Disorders, Chronic Diseases, Growth Hormone Deficiency, Oncology and Others. The report also encompasses the market analysis for product segments - Monoclonal Antibodies, Erythropoietin, Human Growth Hormone, Insulin, G-CSF, Interferons and Others.

This 354 page global market report includes 149 charts (includes a data table and graphical representation for each chart), supported with meaningful and easy to understand graphical presentation, of the market. The statistical tables represent the data for the global market by geographic region, application area and product segment.The report covers the brief business profiles of 43 key global players and 54 major players across the United States - 13; Europe - 18; Asia-Pacific - 19 and Rest of World - 4. The report also provides the listing of the companies engaged in research and development, manufacturing, processing, supplies and distribution of biosimilars. Also enlisting the academic institutions and industry associations engaged in biosimilars, the global list covers the addresses, contact numbers and the website addresses of 168 companies.

Key Topics Covered:

Part A: Global Market Perspective

1. Introduction
2. Biosimilar Applications - A Snapshot
3. Regulatory Landscape
4. Key Market Trends
5. Key Global Players
6. Key Business Trends
7. Global Market Overview

Part B: Regional Market Perspective

Regional Market Overview

1. The United States
2. Europe
3. Asia-Pacific
4. Rest Of World

Part C: Guide To The Industry

1. North America
2. Europe
3. Asia-Pacific
4. Rest Of World

Part D: Annexure
1. Research Methodology
2. The Questionnaire
3. Feedback

Charts & Graphs

Companies Mentioned

• 3SBio
• Amgen
• Astrazeneca
• Baxter International
• Biocon
• Biogen IDEC
• Bioton
• Cadila Healthcare
• Celltrion
• Daiichi Sankyo Company
• DSM Biologics
• GE Healthcare
• Glaxosmithkline
• iBio
• Merck
• Mitsubishi Tanabe Pharma Corporation
• Mylan
• Novartis
• Perkinelmer
• Pfizer Inc
• Roche Holding
• Samsung Biologics
• Sandoz International
• Sanofi
• Shantha Biotechnics
• Watson Pharmaceuticals
• Wockhardt Limited

For more information visithttp://www.researchandmarkets.com/research/wlm2kp/global

Biosimilars take center stage 2013

2013 was a landmark year for the development of biosimilars. With the global acceptance of biosimilars--also called "follow-on biologics" or just "biologics"--and many new approvals, these drugs are moving to a global supply. This is a real and measurable change for the better, and with the global biosimilars market expected to double by 2017, this could be the single fastest-growing biologics sector in the next 5 years. However, despite many U.S.-based companies producing biosimilars, a clear approval pathway for biosimilars by the FDA is lacking. From that perspective, perhaps this year is not a complete success for these biologic medical products.  

Biosimilars continue to be the catalyst for a global revolution in the development of biologics, from a niche market, to encroaching on the small-molecule drugs, to its present status as the largest area of investment in new drugs. All of the big pharmas now have a healthy pipeline of biologics and nearly all have a biosimilars division or partnership. Indeed, partnership seems to be the main vehicle driving the development of biosimilars, and these are still evolving. The main reason for the optimism for biosimilars in Europe and many other countries is simple economics: the need to reduce the overall cost of healthcare. Most forecasts reflect anything from a healthy to a meteoric rise for revenue from biosimilars; one prediction sees a global market for biosimilar monoclonal antibodies of over $19 billion by 2018.

The cost of developing a biologic drug is approximately $800 million. These sums are not for the faint-hearted, but returns can be significant. For example, Enbrel from Pfizer ($PFE) and Amgen ($AMGN) yields annual global sales of over $8 billion. Because of the cost and attendant risk of developing a new biologic drug, until relatively recently many in the pharmaceutical industry saw this as a niche area, buying or licensing successful biologics-based drugs in later stages of development rather than developing their own. Nevertheless, biologics continue to be developed at a rapid pace, as they have the ability to treat conditions that are unresponsive to other drugs. In 2012, 5 of the top 10 best-selling medicines were biologic drugs. Humira, Herceptin and Avastin, for example, have become commonly used in oncology and elsewhere.
The global trend is clear, but in the U.S., it's a different story. It was hoped that in 2013 the FDA would finally issue guidelines for the approval of biosimilars, but unfortunately this has not yet come to pass. Sadly, the FDA's approval pathway places developers of biosimilars at a disadvantage, as they must disclose the dossier used as part of the approval--an unusual step not required by European guidelines. The industry waits with bated breath to see where the FDA will finally settle on this issue.
The near-global introduction of biosimilars has highlighted a number of challenges for the industry. Alongside the need for new production facilities, there is now a considerable analytical requirement for the characterization of biologic molecules, particularly monoclonal antibodies. The innovator product is not usually a single molecular entity but rather a population of molecules in a single batch, and each batch produced will be slightly different. Every vial of product is a mix of molecules, each of a slightly different composition.
Many CROs can provide detailed molecular analysis of the biosimilar in comparison to the innovator. These methods can often pick out subpopulations of molecules with different structures or sugars, or some types of aggregations of molecules, or even degradation of the amino acid backbone. These techniques are extremely useful in assessing the primary comparability of biosimilar to innovator, but these chemistry techniques rarely shed light on the clinical efficacy of these molecules. The biological assessment/comparability of the biosimilar can often be much more illuminating as to the clinical effectiveness. Biological potency assays in vitro mimic some or all of the in vivo biological activities expected from the drug.
One interesting question with respect to differences between innovator molecules and biosimilars relates to impurities, particularly product-related impurities. Frequently, aggregates of the monoclonal antibody are seen in batches of the innovator molecule. This can be seen as an impurity, as it may reduce the amount of available "active" molecules and may also provide a center for immunogenic reactivity. If the biosimilar has less of these aggregates, is this seen as a positive? Or, as these were part of the makeup of the innovator, should these aggregates be maintained at the same level? Such questions will crop up more and more as the field develops.
As we near the end of 2013, the biosimilars story is by no means complete. We in Europe have already seen a number of approvals, with the rate likely to increase over the next few years, but even here it is still very early stages. The next important issue will be the interchangeability of these drugs.
In 2013 the biosimilars industry made significant progress, but a number of hurdles remain globally, not least with the FDA.

RCA: il contributo SSN dal 2014 sarà indeducibile per tutti

Con il decreto IMU è stata introdotta l’indeducibilità ai fini IRPEF/IRES/IRAP del Contributo alServizio Sanitario nazionale (CSSN) connesso alle polizze RCA, a decorrere dal periodo d’imposta in corso al 31/12/2014.

La conversione del DL 102/2013 sembra, quindi, recare effetti generalizzati per imprese e professionisti, oltre che per i soggetti IRPEF; pertanto, da UNICO 2015, non si potrà più indicare nel rigo RP21 l’onere deducibile.

Per quanto riguarda imprese e professionisti, ad oggi, le spese di assicurazione relative ai veicoli sono deducibili dal reddito del 10,5% dei premi dovuti, anch’esso deducibile nella stessa percentuale del premio. Pertanto, a partire dal 2014, considerato che la norma si riferisce genericamente alle imposte dirette, sembra necessario scomputare dal costo dell’assicurazione il predetto contributo al fine di renderlo integralmente indeducibile nella determinazione del reddito d’impresa e di quello di lavoro autonomo.

Ciò, avrà un impatto sia amministrativo, in quanto diventa consigliabile sdoppiare la registrazione contabile del premio assicurativo, che economico, in quanto per alcune fattispecie la deducibilità dei costi era rimasta invariata anche a seguito della cd “riforma Fornero”.

Si tratta, ad esempio, delle società di noleggio per le quali i costi relativi alle autovetture sono deducibili in misura integrale, ovvero delle auto date in uso promiscuo ai dipendenti i cui costi sono deducibili nella misura del 70%. In tutti gli altri casi, si dovrà evidenziare un costo indeducibile che, diversamente, sarebbe stato deducibile nella al 20%. In realtà, più che il maggior onere (in molti casi irrisorio) sarà seccante, per gli addetti ai lavori, gestire un’ulteriore variazione in aumento.

Spending review: in Sanità risparmi per 10-15 mld in 5 anni

La spending review colpisce duramente la sanità. Dal Ministero della Salute arrivano stime che prevedono risparmi dai 10 ai 15 miliardi nell’arco dei prossimi 5 anni attraverso una riorganizzazione e riqualificazione della spesa.

In un’intervista sulla stampa nazionale, il Ministro della Salute Lorenzin sottolinea che arrivare alla cifra di 15 mld sarebbe un grande successo ma metterebbe “la firma” se si arrivasse a 10 miliardi. I risparmi sono comunque da reinvestire in sanità, ha affermato il ministro, sottolineando che le regioni non possono tirarsi indietro, ne va della sostenibilità del Ssn.

“Dopo la cura dimagrante degli ultimi anni, i tagli lineari non servono più. Adesso è necessaria la riorganizzazione e la riqualificazione della spesa e l’attuazione di misure che giacciono inapplicate”, spiega Lorenzin, ricordando che bisogna puntare sul “Patto per la salute“.

Il ministero dell’Economia punta a raccogliere con la spending review circa 32 miliardi tra il 2014 e il 2016, migliorando la qualità dei servizi e riducendone il costo.

La legge di Stabilità prevede che la spending review produca risparmi per complessivi 3,6 miliardi nel 2015, 8,31 nel 2016 e 11,31 miliardi a regime dal 2017. I tagli aggiuntivi peseranno quindi per quasi 24 miliardi sul bilancio del 2016.