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.
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.