Tag Archives: inhaler

Create Greater Patient–Value To Excel With Repurposed Covid Brands

Posted on by
Reply

Regular introduction of new molecules, line extensions or a Novel Drug delivery System (NDDS) has remained the life blood for pharma to rejuvenate a company’s product portfolio for driving organizational growth. But, Covid’s unprecedented and devastating assault on human lives and livelihoods, has pushed many of these initiatives off track. Covid infection was declared pandemic by the World health organization (WHO) on March 11, 2020, compelling the industry to primarily focus on finding solutions for survival, especially in the product development areas.

As the fight against time, the need for survival became so intense, there was no time for pharma companies going back to primary research, to discover new effective Covid specific drug molecules. Vaccines – at the initial stage of the pandemic, were considered by experts could be the only ‘magic bullet’, to get the humanity back again on its feet, after a fierce knockout blow by the virus. As on date, although vaccines seem to be nearer the finishing line of creating adequate initial immunity against Covid, still there are no scientifically proven drugs to predictably cure this infection.

Meanwhile, the focus of all concerned is on the existing drugs, to examine their effectiveness against Covid-19. Accordingly, right from hydroxychloroquine, dexamethasone to a number of already existing antiviral agents were repurposed for Covid treatment, under emergency approval by country regulators, pending detailed clinical trials.

For various critical reasons, experts now feel that the use various NDDS technologies in repurposing existing drugs, would create greater value for patients in Covid treatment. At the same time, this will help pharma companies to create a cutting-edge differentiator for their repurposed brands – being more patient centric. In this article, I shall dwell in this area, starting with the current status and issues with repurposed Covid drugs, as of date.

Current status and issues with repurposed Covid drugs:

According to recent reports, such as one titled ‘Formulation and delivery strategies for COVId-19 drugs,’ published by the AIchE in June 2020, more than 40 different drugs are currently being explored for efficacy against COVID-19. Unfortunately, side effects of many of these repurposed drugs limit their use in most severe cases, besides preventing their use as prophylactics.

A large proportion of repurposed Covid drugs are small-molecule medications, antivirals, and immune-modulating antibodies. These are already approved for other indications (like hydroxychloroquine, ribavirin, favipiravir), or under clinical trials, but not yet approved by the U.S. Food and Drug Administration, FDA (like, remdesivir, galidesivir, leronlimab).

If proven effective, these drugs would offer several advantages from a rapid- response perspective, such as the availability of safety data. In addition, several of these drugs offer broad-spectrum activity that makes it more likely they will remain functional even if the SARS-CoV-2 virus mutates. However, there are also exists some critical issues with repurposed Covid drugs.

Some critical issues with repurposed Covid drugs:

Let me cite below two examples, just to drive home the point of some critical medical issues, now existing with these repurposed Covid drugs:

  • Hydroxychloroquine – the malaria drug, when used as directed, commonly produces nausea, diarrhea, vomiting, besides muscle weakness. Importantly, at higher concentrations – only two to three times the daily dose, it can cause potentially fatal acute cardiovascular toxicity. Thus, the possibility of severe side effects makes the drug unattractive as a preventive measure. Drug formulation and delivery strategies, such as controlled release and targeted delivery could expand the use of such existing drugs, the report recommends.
  • The HIV drug combination lopinavir and ritonavir, which is under evaluation as a COVID-19 treatment, has side effects that include diarrhea, nausea, and liver damage. With a half-life of about 4–6 hours, the systemic concentrations can vary by a factor of eight between peak and trough. Developing a controlled-release formulation that maintains the minimum effective drug concentration, could mitigate side effects by reducing the steady-state drug concentration by as much as eightfold and reducing the burden on the liver by 81%, the above study, published by the AIchE in June 2020, highlighted.

At this point, for greater clarity, let me recapitulate what NDDS really means.

NDDS – clinical and marketing relevance:

Novel Drug Delivers Systems or NDDS generally ‘refers to the approaches, formulations, technologies, and systems for transporting a pharmaceutical compound in the body as needed to safely achieve its desired therapeutic effects.’

This process was lucidly explained in a contemporary article, which also inferred that the method by which a drug is delivered can have a significant effect on its efficacy and safety profile.

Yet another paper underscored, ‘if therapeutic agents can be made more efficacious and safer, using an improved drug delivery system, could achieve both –lucrative marketing opportunities for pharmaceutical companies, alongside advancement in the treatment of diseases of mankind.’ Moreover, NDDS can also help maintain the drug concentration in the therapeutic range for a longer period of time and deliver the content to the site of action if required.

Leaving aside the technical details behind these mechanisms let me underscore - that NDDS will be a boon for the repurposing of drugs, was also discussed in detail in an article titled, ‘Role of Novel Drug Delivery Systems in Coronavirus Disease-2019 (COVID-19): Time to Act Now,’ published on September 09, 2020.

Some broad categories of NDDS and new initiatives:

For this purpose, some of the broad categories of NDDS may include the following:

  • Sustained- or controlled drug delivery systems provide drug action at a pre-determined rate.
  • Localized drug delivery devices for drug release in the vicinity of the target.
  • Rate – pre-programed drug delivery systems.
  • Targeted drug delivery provides drug action by using carries, which recognize their receptor at the target.

It goes without saying that NDDS mechanism may be used both for new molecules that may eventually be developed, and also for the existing repurposed drugs for Covid treatment.

Some encouraging initiatives of NDDS for Covid drugs:

The encouraging news is pharma initiatives in this regard has already commenced. For example, unprecedented interest in inhaled delivery of antiviral drugs has led to Aerogen’s involvement in multiple COVID-19 drug development initiatives, with more than 15 leading pharmaceutical companies - worldwide.

Several of these collaborations are already in clinical trials. Others are also on track to enter studies on moderately and severely ill COVID-19 patients, the Press Information of Aerogen dated October 22, 2020 highlighted. Let me cite below two more examples in this area, to explain the intensity of work that has commenced in the NDDS space for repurposed Covid drugs.

Covis Pharma’s inhaled glucocorticoid, Alvesco (ciclesonide) has entered Phase III safety and efficacy trial in 400 non-hospitalized patients  -12 years of age and older with symptomatic COVID-19. The product is delivered twice daily via a pressurized metered dose inhaler (pMDI).

Senzer Pharmaceuticals - a UK based company, is also in the process of formulating two specific medicines with antiviral properties, to allow them to be inhaled directly into the respiratory tract. The primary aim is to reduce the number of COVID-19 patients requiring intensive care treatment. Senzer is also using a pMDI for targeted drug delivery of actives through inhalation, as it offers potential advantages over oral intake. These include, ease of administration, assisting early treatment, allowing a lower dose by reducing unwanted side effects and supporting the safety profile of the products.

Experts consider preparations of inhalable particles for local delivery is a simpler approach. This is because the lungs comprise only about 2% of the total body weight, targeted delivery could reduce the amount of drug required by a factor of 50 or more, as compared to oral administration.

Be that as it may, the primary purpose of all such initiatives is to ensure more effective and safer drug delivery to Covid patients. It is now up to the pharma marketing leadership to ascertain how to leverage such NDDS opportunities to deliver extra patient-value, simultaneously creating a cutting edge for marketing these repurposed brands.

Impact of Covid on the NDDS market segments:

The May 11, 2020 report titled, ‘Drug Delivery Systems Market Forecast, Trend Analysis & Competition Tracking – Global Market Insights 2020 to 2025,’ presents some interesting details in this area. It forecasts, the global drug delivery systems market shall register an upswing, expanding at a strong CAGR of 7.0% during the forecast period (2020-2025).

The ongoing COVID-19 pandemic is expected to further heighten prospects of NDDS, with the number of infections still increasing every day. Consequently, many leading pharma companies have accelerated production of essential drug delivery systems, as stated above. According to the above report, the key growth drivers of the NDDS market include:

  • Targeted drug delivery - being most dominant, is expected to capture nearly half of the global NDDS market, expanding at a healthy CAGR of 6.8% across the above forecast period.
  • Polymeric drug delivery segment is anticipated to be the second-most lucrative area, expanding at a CAGR of 7.3% across the forecast period. The popularity of this delivery type is attributed to its efficiency in localized drug delivery in large amounts, alongside lowering drug toxicity rate. The polymeric drug delivery segment is expected to capture more than 1/3rd of the global drug delivery systems market during the forecast period.
  • Application of nanotechnology is another key growth determinant for the segment. Insertion of nanoparticles help penetrate the targeted tissue in a much better manner. These particles are easily absorbed by cells, facilitating efficient drug delivery.
  • Microneedle drug delivery helps deliver vaccines or other drugs across various barriers.

Conclusion:

The Covid clock keeps ticking. As on November 22, 2020 morning, India recorded a staggering figure of 9,095,908 of Coronavirus cases with 133,263 deaths. The average number of daily new cases appeared, after the festive season, have started climbing up again. The threat of subsequent waves for further spread of Covid infection now looms large.

In this regard, many experts initially thought that Covid vaccines will be magic bullets to win the war against the new Coronavirus. But in the most recent times, this situation has changed, and it is no longer so – not even Pfizer vaccine. Indian media also deliberated the same on November 05, 2020.

Under this backdrop, Arthur L. Caplan, professor of bioethics at New York University’s Grossman School of Medicine, who wrote a 2017 book on vaccine ethics and policy have also made a profound comment. He said recently: “We’re going to have to continue our behavioral efforts - the masking and distancing and the quarantining and the testing and so on — in parallel with vaccination because it would be very, very surprising if we got a very highly effective vaccine first one out of the box.”

Currently, the world doesn’t have any clinically proven new Covid treatment drugs, either. What we have now is a number of repurposed Covid drugs, many of these are in advanced stage of clinical trials. As and when these are approved by the country’s regulators, pharma marketers will have a task cut to excel with those – among many ‘me-too’ types. In this scenario, there will be a critical need to create greater patient-value with a company’s own repurposed brand, where right application of NDDS technology could play a game changing role. The time to keep pondering is over. Time to decide is – now.

By: Tapan J. Ray     

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

 

 

2015: Pharma Industry Achieved Some, Could Achieve Some More

Posted on by
Reply

Wish You And All Your Near And Dear Ones Peace, Happiness, Good Health And Prosperity in The Brand New Year 2016 

The year 2015 witnessed several noteworthy developments in the pharma industry, just as many other years before. That said, in my view, a few of these happenings were much more impactful, and probably took place for the first time ever, in the year just gone by.

Obviously, one such major development is the overall serious adverse impact on the image of the pharma industry, in general. 

During 2015, the image of the pharma industry got further tarnished by reports of high-profile alleged drug price manipulations. This avoidable saga culminated with the arrest of a pharma Chief Executive Officer (CEO) in the United States, amid a federal investigation, in December 2015.

However, I am not going to dwell on this issue in this article. Instead, I shall select some key strategic pharma business areas, which contribute to the largest chunk of the total overall cost, incurred by the global pharma industry, every year. These areas, as I see, are:

  • Drug discovery research
  • Sales and Marketing
  • Supply Chain
  • Development of new drug delivery systems
  • Patients care and engagements

I have put all these points in the above order, just for the convenience of my discussion in this article. 

With a few examples, I shall give my perspective on these areas of the global pharma industry, dividing them broadly into the following two sub-categories: 

  • Areas where the industry could have done a lot better
  • Areas where the industry made significant progress
The Pharma industry strategy continues to remain broadly traditional:

Pharma sector is globally considered as an industry, which appears to be more comfortable in maintaining and harnessing its traditional approaches, in almost all its field of activities. Although, some tweaking has certainly been taking place, which are primarily to automate or digitalize the same process, aimed at adding more speed together with virtually real time monitoring of operations.

Let me hasten to add here that, some major and newer types of modern tech based collaborative initiatives with large companies outside the pure pharma space, have also been reported, during the year.

I shall deliberate on both these areas, one after another, hereunder. 

A. Areas where the industry could have done a lot better:

Drug discovery research:

With the increasing impact of patent cliff and low productivity in drug discovery research, coming alongside big ticket generic threats, many pharma players seem to be still tweaking with its traditional blockbuster drug discovery model, in 2015.

Slightly changing from this traditional strategic focus, many of them have now started focusing more on ‘Orphan Drug’ research, though with indication of a life threatening disease with low prevalence, intending to go whole hog for very high pricing of these drugs.

By gradually adding more indications, these innovator companies plan to make the ‘Orphan drug’ molecule a money churning blockbuster drug. As a result, the number of venture capitalists, who invest in the early stages of such drug development, has increased significantly in 2015.

According to reports, over 40 percent of all approved orphan drugs are meant for high risk cancer sub-categories with low prevalence rate. Although these drugs are for lifetime treatment, the medicines are frightfully expensive, costing between US$200,000 and US$300,000 per year, for each patient. 

Intriguingly, still a very few drug companies are externalizing drug discovery research or even considering on a large scale, the use of the ‘Open Source’ drug discovery model, which is currently widely used in the Information Technology (IT) industry, as one of the main platforms to get new products.

Sales and Marketing:

Similarly, in the pharma sales and marketing space, there has been no game changing developments, during the last year.

Although, some initiatives that can at best be termed as tweaking on the traditional pharma methods, were visible, especially in the fields of digital marketing and e-detailing. The good old and much tried traditional tools, such as, Medical Representatives’ (MR) product detailing to individual doctors or a large number of ‘medical seminars’/ ‘continuing medical education’ events, of varying scale and dimensions, arranged for the medical practitioners, still ranked at the very top of this domain. 

Here, again, no signs of a paradigm shift were visible to me during the year, nor do I reckon, any game changer is likely to surface, any time soon.

Supply chain:

The immense importance of ‘Supply Chain’ in the overall pharma business does not appear to have been properly understood by the drug companies up until 2015. This has been well vindicated by various credible studies. I would refer below just two of those: 

The Chief Supply Chain Officer Report of September 2014, highlighted that just 39 percent of pharmaceutical respondents see the ‘Supply Chain’ as an equally important part of business success as R&D or sales and marketing. Whereas, 68 percent of consumer packaged goods’ respondents believe that leveraging the true potential of this domain, is one of the key requirements for business excellence.

This is noteworthy, as even ‘The McKinsey report’ of September 2013 stated that supply chains now account for around 25 percent of pharmaceutical costs. The annual spending on it is so staggering of around US$230 billion that even minor efficiency gains in this area could free up billions of dollars for investments elsewhere.

Instead of following its traditional approaches, if the pharma sector adopts even straightforward advances, well established in other industries, the total costs could fall by US$130 billion, ‘The McKinsey report’ estimates. 

Ideally, pharma ‘Supply Chain’ should be considered not just a means of getting the products at the right place, at the right time and in the right quantities, but also as a means of delivering additional value to the customers. This can be achieved with radical strategic intervention in this space with the application of the state of art technology, which was still broadly lacking in 2015. 

B. Areas where the industry made significant progress: 

In this section, by citing examples on two other important strategic business areas of the pharma industry, where significant progress has been reported during 2015, I would try to drive home my point. These two areas are new drug delivery systems and patient care/engagement.

New drug delivery systems:

On the development of new drug delivery systems, some interesting collaborative arrangements have been reported in 2015. As illustrative examples, I would cite just the following two: 

A. “Smart Inhaler”

I have picked up this important area of a new drug delivery system, out of many, as it fascinates me immensely. Here again, I would illustrate my point with just two examples – out of several others, as hereunder:

1. On December 2, 2015, the British drug major GlaxoSmithKline (GSK) reportedly entered into a technology deal with Wisconsin-based Propeller Health. Under this collaboration, Propeller will create a custom sensor for GSK’s Ellipta inhaler. The Propeller platform combines sensors, software, and care team services to improve patient outcomes by providing more insightful and efficient care. GSK is the second largest pharmaceutical company to partner with Propeller Health, which in December 2013 announced a deal with Boehringer Ingelheim to develop a custom sensor for BI’s Respimat device.

2. In September, 2015, Teva Pharmaceuticals reportedly acquired Cambridge, Massachusetts-based Gecko Health Innovations, a smart inhaler company.

Gecko’s main product is a platform for chronic respiratory disease management that also combines a sensor device that connects to most inhalers, a data analytics platform, an accessible user interface, and behavioral triggers to help asthma and COPD patients manage their condition, more effectively.

B. Sanofi and Medtronic strategic alliance in diabetes to improve patient experience and outcomes

Although not many large scale commercial ‘drug discovery’ initiatives based on the ‘Open Source’ model is still not known to me, in the ‘new drug delivery system’ area, a major global strategic alliance, between Sanofi and Medtronic in the diabetes therapy area, has been reported based on this model. This alliance is aimed at improving patient experience and outcomes for persons with diabetes, around the world. 

As I mentioned, the alliance structured as an ‘Open Innovation’ model, will initially focus on the following key priorities:

  • Development of drug-device combinations
  • Delivery of care management services to improve adherence and simplify insulin treatment
  • Help people with diabetes better manage their condition

Patient engagement and care:

Quite encouragingly, in the ‘patient engagement and care’ area too, some of the global pharma majors have taken notable tech-based strides during 2015. Some of these laudable ventures are as follows:

A. Novo Nordisk and IBM partner to build diabetes care solutions on the Watson Health Cloud

According to a Dec. 10, 2015 ‘Press Release’, Novo Nordisk and IBM Watson Health agreed to work together to create diabetes solutions, built on the Watson Health Cloud.

Under this agreement, by harnessing the potential of the Watson Health Cloud, Novo Nordisk aims to further advance its offerings to people living with diabetes and also their health care professionals.

B. Sanofi collaborates with Google to Improve diabetes health outcomes

Less than a couple of months before the Novo Nordisk – IBM partnership agreement, by a Press Release of August 31 2015, Sanofi and Google announced their collaboration to improve care and outcomes for people with type 1 and type 2 diabetes.

According to the release, this collaboration will explore how to improve diabetes care by developing new tools that bring together many of the previously siloed pieces of diabetes management and enable new kinds of interventions. This includes health indicators such as blood glucose and hemoglobin A1c levels, patient-reported information, medication regimens and sensor devices. 

Is the word “Innovation” also being used as a façade?

This important, though contentious issue, is being raised by many today, globally.

In my view, global pharma even in 2015, continued making the mistake of repeatedly highlighting, with high decibel sound bytes that the stakeholders do not understand the value, importance and necessity of innovation, which in any case is far from the truth. Nevertheless, It kept using, rather more misusing, this important word too often to cover up any action of theirs that faced government, general public or media scrutiny.

Additionally, many pharma players seemingly continued to remain contented with a very narrow definition of the word ‘innovation’, limiting its application mostly in the traditional space of drug discovery. While at the same time, many other smarter and more astute innovators, especially in the IT world, besides Google, IBM and Apple, started stepping into the vast healthcare arena, which otherwise could possibly have become pharma’s expanded market.

A am quoting below the names of just five of these amazing innovators, from the published data, just to give you a feel of this interesting area of ‘innovation’ in the health care arena:

  • Medivation: For finding the value of treatments that others ignored
  • Beijing Genomics Institute: For making DNA sequencing a mass-market
  • Medisafe: For using wireless and cloud technology to improve drug adherence
  • Ginger.IO: For harnessing behavioral data to save lives
  • Setpoint Medical: For creating a built-in pain-relief platform 
Epilogue:

Overall, the year 2015 was a mixed bag for pharma. Many pharma players, I reckon, displayed their self serving intent in a more glaring manner. Several captains of this industry generally talked all right things, which are music to many ears, but mostly acted quite differently, going against the public health interest, as reported by the global media.

Many pharma companies continued trying to woo the media cleverly during the year. Some of them, reportedly, even sponsored trips of a few Indian journalists to their respective overseas headquarters. As I understand, many newspaper readers too, had noticed the small print disclosures in this regard, at the bottom of their stories on those companies, written on the return.  I have no intention to be judgmental on such trips. Nevertheless, the global media, including the Indian media, by and large, reported all such deeds, with as much detail as possible, without slightest hesitation.

Encouragingly, a few global pharma majors, such as, Sanofi, Novo Nordisk, GlaxoSmithKline and AstraZeneca challenged this contusing status quo in 2015. They seem to dare to chart into the much uncharted frontier to squarely face the challenge of the changing demands of the changing world order. Probably not so much by trying to change others, but mostly by changing themselves. 

It appears, at least, the likes of the above global players have started accepting the new expectations of the aspiring customers and their fast transforming mindsets, including, the tougher governments enacting contemporary laws and regulations in many countries. In tandem, the exorbitantly high cost and usually low profile advocacy initiatives of drug companies seem to becoming lesser and lesser productive, as evident by the increasing number of avoidable issues that the pharma industry is now facing. Added to all this, a modern and major force-multiplier, in the form of social media, has now started unleashing its unfathomable power of shaping laws, regulations and even public opinion.

I wish this wind of change gaining more speed in 2016, and in that process, ushers in the long awaited dawn of a new paradigm. A paradigm of justice and equity in health care for all, across the world, and especially to my own country – India.

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

Does Patent Expiry Matter Less For Difficult To Copy Drugs?

Posted on by
Reply

“Patent expiry matters much less for difficult to copy drugs”.

Not so long ago, this is what many used to believe in the pharma industry. However, looking at the current trend involving the tech savvy generic players, it appears, gone are those days even for the home grown companies in India. As we witness today, a number of global generic players, including some from India, are overcoming the tough challenge of technological barrier of the original drugs with technology, boldly and squarely, and that too with reasonably good speed.

A global CEO felt quite the same:

Possibly encouraged by this commercial dogma, the Chief Executive of GlaxoSmithKline (GSK) Sir Andrew Witty reportedly felt in not too distant past that his company’s blockbuster drug Advair/Seretide, used for the treatment of asthma, would continue to remain a major product, despite losing US patent in end 2010. Witty thought so considering the intricate technology involved in making its high tech inhalation drug delivery system with exacting precision.

Technology based entry barrier:

Although, Advair/Seretide is a respiratory inhalation drug, it is not quite like a typical aerosol inhaler consisting of a pressurized canister filled with liquid medicine formulation. In such system, as the canister is compressed, the liquid inside comes out as a spray that is breathable in an amount as required for desirable clinical efficacy for the patients.

With the application of complex technology, Advair/Seretide was formulated not as a liquid, but as pre-determined fixed dose combination of powders that patients inhale into their respiratory tracts with a device called ‘Diskus’, which involves a complex and difficult to copy inhaler technology with a long patent life.

This precision technology was expected to create the requisite entry barrier for generic equivalents of this important medicine.

“Diskus” patent to continue:

It is important to note, though Advair/Seretide had gone off patent in end 2010, the patent protection for the “Diskus” device that dispenses the powder version of the fixed dose drugs combination, continues till 2016. For the inhaler device that dispenses the aerosol version of the same drugs, the patent remains valid until 2025.

New USFDA guidance:

Keeping these factors in mind, the USFDA in its latest guidance has clearly enunciated the characteristics that an inhaler should have, including a similar size and shape to Diskus. This new USFDA guidance for inhaled drugs, like Advair/Seretide, now requires only “relatively basic” preclinical tests and a short clinical trial.

Many believe that this new guidance is mainly to ensure that other generic devices also qualify for the GSK’s asthma drug combo, after its patent expiry.

Nevertheless a challenging task:

Despite this new USFDA guidance for inhaled drugs, some large generic manufacturers apprehended, even way back in 2010, that they doubt whether it will be possible for them to adequately replicate Advair/Seretide to meet the stringent “substitution” requirements of the USFDA on generics. This is exactly what Witty had envisaged earlier.

Almost two years after its patent expiry, in October 2012, the world’s largest generic drug maker Teva also announced that the company does not expect to see true substitutes for Advair/Seretide before 2018.

No immediate sales impact post-patent expiry:

As a result, in 2012, even a couple of years after its patent expiry, Advair/Seretide could successfully weather the impending storm, though GSK reported a lackluster overall business performance. The brand at that time was virtually immune to substitution threats from generic equivalents. The key reason being, as stated above, much unlike a patented chemical drug substance, the ‘Diskus’ system of the GSK inhaler is a hell of a task to copy by meeting the regulatory requirements of substitution.

In 2013, close to three years after its patent expiry, Advair/Seretide ranked fourth within the top 10 global best-selling drugs of that year, clocking annual revenue of US $8.25 billion.

The first competition:

In the midst of all these, the first generic equivalent of Advair/Serevent with a new inhalation device, carrying a name AirFluSal Forspiro from the Sandoz unit of Novartis, started warming up to obtain regulatory approval from several countries within the European Union (EU).

The product was first approved in Denmark on December, 2013 with subsequent marketing authorizations received in Germany, Sweden, Hungary, Romania, Bulgaria, and Norway.

The heat started being felt now:

The overall position of the brand started changing thereafter. According to published reports, sales trend of Advair/Seretide in Europe and other markets are on the decline in 2014. In Europe, the drop was around 3 percent and in the US around 19 percent in the last quarter, due to a combined impact of many factors.

According to Bloomberg, the sales of Advair/Seretide are expected to drop from US$8.25 billion in 2013 to US$5.9 billion in 2016 with the entry of generics.

A large and growing market to invest into:

According to the World Health Organization (WHO), in every 10 seconds, Chronic Obstructive Pulmonary Disease (COPD) that includes conditions such as chronic bronchitis and emphysema kills one person globally. It is expected to be the third leading cause of death worldwide by 2030.  However, though more number of people suffers from asthma globally, its mortality rate is still much less, WHO says.

Bloomberg estimates that COPD market, including asthma, is expected to reach over US$30 billion by 2018.

Cipla came next crossing the ‘technology hurdle’:

Though the leader in the global generic market – Teva, expressed its inability to introduce the generic version of Advair/Seretide before 2018, this month, the Indian pharma major Cipla introduced its version of the product in two European countries, just next to Novartis. Consequently, Cipla demonstrated its ability to overcome the technological hurdle of the product faster than most others and mastering the intricate NDDS technology in record time, with precision.

The Cipla product is named as ‘Serroflo’ in Germany and ‘Salmeterol/Fluticasone Cipla’ in Sweden. As reported in the media quoting Cipla Chairman Dr. Yusuf Hamied, the product has also been launched in Croatia. By now, Cipla has obtained regulatory approvals of this product in 10 countries in total, with an approval pending in the GSK’s own domestic turf, the United Kingdom (UK). Other country-wise launches in Europe would probably take place much before the end of 2014, according to Dr. Hamied.

The product is expected to be launched in the US in the next three to four year’s time, though one media report mentioned about its 2015 launch in that market. Dr. Hamied also said that his company is now planning its first-ever manufacturing plant in America, which might focus on producing HIV medicines.

On a conservative estimate, the market analysts expect Cipla to generate around US$50 million in sales from the EU markets by 2016 and around US$110 million by 2018, as the company gains increasing market access with not more than 4-5 generic competitors competing in this segment.

Be that as it may, getting regulatory approval for launch of a generic version of Advair/Seretide in the regulated markets, by itself, is a huge achievement of technological prowess that Cipla has demonstrated, yet again.

Not too many generic competition expected:

Because of high quality technological requirements to develop a replaceable generic version of the GSK product, not too much competition is expected in this segment.

Thus far, another global generic drug major Mylan is expected to file for a generic version of Advair/Seretide in the US by the third quarter of 2015 for a 2016 launch. Besides Cipla and Novartis, Mylan, Teva and Actavis are expected come out with the generic version of this drug.

Opportunities in ‘difficult to copy’ drugs:

According to a recent ‘RnR Market Research Report’, over 1,400 drugs with New Drug Delivery System (NDDS) have since been approved globally. This includes inhalation devices too.

The oral drugs contribute the largest share of the overall NDDS market with over 52 percent of the total pie. This segment is expected to attain a turnover of over US$90 billion by 2016 at a CAGR of 11 percent. The injectable new drug delivery market is expected to reach a turnover of over US $29billion by 2015, according to this report.

I have deliberated this subject in one of my earlier blog posts titled. “Moving Up The Generic Pharma Value Chain”.

Another high tech area – biosimilar drugs:

As the high priced biologic drugs of the innovator companies go off patent, large molecule biosimilar drugs, involving high technology, would emerge as another lucrative growth opportunity for the generic players having requisite wherewithal.

Recombinant vaccines, erythropoietin, recombinant insulin, monoclonal antibody, interferon alpha, granulocyte cell stimulating factor like products are now being manufactured by a number of domestic biotech companies. Some of the Indian companies that have already entered into the biosimilar segment are Dr. Reddy’s Laboratories (DRL), Lupin, Biocon, Panacea Biotech, Wockhardt, Glenmark, Emcure, Bharat Biotech, Serum Institute, Hetero, Intas and Reliance Life Sciences, besides others.

The ultimate objective of all these Indian companies is to get regulatory approval of their respective biosimilar products in the US and the EU either on their own or through collaborative initiatives.

Overall improvement in the quality of ANDA filings:

In the last few years, overall quality of ANDA filings of the domestic Indian pharma players has also improved significantly. Their regulatory filing schedules now include many complex molecules, injectibles, oral contraceptives, ophthalmic preparations, inhalers/other drug delivery systems and biosimilars, beside Para IV/FTFs. All these are now contributing a growing share in their new product initiatives for the regulated markets.

Conclusion:

In the largest pharma market of the world – the United States, global generic companies are increasingly facing cutthroat price competition with steep price erosion, registering mixed figures of business performance and growth.

However, a new trend is fast emerging. Even when global innovator companies are including increasing number of difficult to copy medicines in their product portfolio, some pharma players are reaping a rich harvest by moving up the value chain with the generic versions of those products, post patent expiry. These copycats offer much higher margin than non-differentiated generics.

Some Indian generic companies too have started focusing on building value added, difficult to manufacture, and technology intensive generic product portfolios in various therapy areas. DRL is reportedly all set to take its complex generic drug Fondaparinux sodium injection to Canada and two other emerging markets.

Those Indian pharma companies, which would be able to develop a robust product portfolio of complex generics and other differentiated formulations for the global market, would now be much better placed in positioning themselves significantly ahead of the rest, both in terms of top and the bottom line performance.

The myth, as epitomized in the good old saying, “Patent expiry matters less for difficult to copy drugs”, seems to be partly true in delaying entry of generics immediately after the end of the monopoly period, at least, for now. However, I reckon, this gap of delay would eventually get much reduced, if not eliminated altogether, as we move on. Armed with cutting edge technology Cipla has almost busted the myth, as it came close second to Novartis with the launch of a complex generic equivalent of Advair/Seretide in the EU and other markets.

Pharma majors of the country, such as, DRL, Cipla, Lupin and Biocon, to name a few, are taking great strides, setting examples for many others to emulate and excel in this area. The groundswell has already begun for a long haul global journey of the Indian pharma into the El Dorado of high tech generics fetching higher rewards.

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.