COVID causes chaos and special situations

COVID causes chaos and special situations

“Order brings sameness. Chaos brings newness every moment. The problem is first overcoming our fear of chaos, and then mining for the great ideas and bringing them back home.” (anon.)

Since the start of 2020, and the dawning realisation that something was “not quite right” with the world, chaos has indeed reigned. Bringing with it fear, not only of the chaos, but also of the cause….the novel coronavirus SARS-CoV-2 (COVID)

The COVID-19 pandemic has necessitated the unprecedented use of a number of pharmaceutical agents not only in an attempt to find an effective treatment for the viral infection itself, but also to manage the severe and varied nature of the symptoms associated with this deadly virus.

This has resulted in an increase in the number of (often emergency) situations where drugs have been used off-label and/or resulted in cases of pregnancy exposure or lack of efficacy. From a pharmacovigilance perspective, these “special situations” must be closely monitored to ensure the emerging safety information relating to the use of drugs in such cases, is appropriately recorded and analysed so that subsequent interventions can happen to ultimately guarantee patient safety.

From our experience, the proportion of special situations identified in the literature is approximately 15% of Individual Case Safety studies (ICSRs) reported. During the first half of 2020, the proportion of special situations associated with COVID-19-related drug use has increased by a further 10%…. and this is only the beginning.

Unfortunately, while the virus has increased the number of drug safety events worldwide, it has simultaneously reduced the resource and potential to record what will become an important phase in the history of global drug safety.

This was recognised by the US FDA when it recently updated its guideline related to post-marketing adverse event reporting during a pandemic.

To ensure that safety data related to medicinal use during the COVID-19 pandemic are captured, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) has set up a designated website, and the EMA has taken a similar approach with its call to action for all patients with COVID-19 to report any adverse events relating to the use of medicinal products they may receive, since it is important to understand the potential drug interactions that patients may experience.

These data-capturing processes are essential in the current “trial and error” situation we find ourselves in. The need for close monitoring of off-label use of drugs is imperative, now more than usual, if industry is to ensure patient safety in the search for the most effective treatment in the absence of a purpose built cure.

This agile approach has been demonstrated by the FDA when it issued two Emergency Use Authorisations (EUAs) for off label use of Remdesvir and also for chloroquine phosphate and hydroxychloroquine sulfate; then, just 11 weeks later, the EUA for chloroquine and hydroxychloroquine was revoked, based on on-going gathering of evidence that indicated these agents may not be effective for the treatment of COVID-19.

Use of azithromycin to protect healthcare workers from the virus was fleetingly entertained in the UK; this glimmer of hope was short lived as evidence emerged to indicate azithromycin was not effective and may have an unfavourable risk-benefit profile especially when given in combination with hydroxychloroquine. This was supported by National Institutes of Health that issued guidelines strongly recommending against the combined use of hydroxychloroquine plus azithromycin, citing potential toxicities, and also against the use of HIV protease inhibitors without evidence of clinical benefit against the disease. Although disappointing, this information is important for patient safety, and in terms of pharmacovogliance the lack of efficacy observed with these and other repurposed drugs will contribute to the growing volume of valuable safety literature.

At the beginning of 2020 an increase in special situation literature safety reports began to emerge as the pandemic swept the globe and the world looked for an effective treatment for this disease. A search of the AdisInsight Safety database confirms that off-label use of lopinavir and ritonavir, alone and combination was associated with adverse events in patients located in China, Japan, Poland France Iran and the US. And pregnancy exposure, to a variety of drugs, was evident particularly in China and the US.

With the unfortunate possibility that we will experience a second wave of COVID-19 infections in countries that seem to have already conquered the disease, hopefully we can learn from the safety information generated during the initial wave and can put it to good use.

The global impact this disease has had on the use of pharmaceutical products is yet to be fully realised. I believe that the volume of safety-related literature is set to soar over the next few years as the information regarding this unique situation is processed and published.

Image: Morning Brew on Unsplash.

AdisInsight strikes again with global, drug-centric patent data

AdisInsight strikes again with global, drug-centric patent data

Year after year our customer research has indicated that end users needed more information about the patent protection for the drugs they were analyzing with AdisInsight.  They wanted to answer questions like when a generic version of a branded drug will be available, which countries are covered and not covered by patent protection, and what patent extension strategies are available to prolong market exclusivity. We studied the current user journeys of our users and found they almost always ended with an expert patent searcher or patent attorney searching one of the existing patent databases because these complex resources require special skill to use them correctly.

In 2017 we set out to enhance the patent information available in AdisInsight. We conceived of a simple and intuitive tool that would allow our users to discover patent information themselves in order to inform strategic decisions.  This would translate into quicker answers and use fewer resources compared to their current approach involving patent attorneys directly.  We had tried this many times before only to find the task of grouping the patents pertaining to a specific drug too difficult. This time our content development team identified and evaluated several potential partners who could provide drug-based patent information. Think BioTech rose to the top due to their ability to associate patents with the specific drugs they apply to.  At the end of 2017 a partnership agreement was reached with Think BioTech (click here to read the press release) to supply AdisInsight with patent content for marketed drugs.

Once the agreement with Think BioTech was in place, stakeholders from product management, content development, IT&P, UX design, and IT developers came together to create the product vision for AdisInsight Patents, mock-up how patent information would be displayed to meet the needs of end users, and develop a plan to implement our MVP.

In March 2018 I went on the road with our lead UX designer, our business analyst, and one of my product manager for AdisInsight to conduct User Experience testing to validate the designs developed met customer needs. We conducted 13 end user interviews across pharma, biotech, and consulting. The results showed that our design placing an emphasis on displaying specific formulations of a drug missed the mark. In true agile form we rapidly arranged another stakeholder meeting to digest the UX findings and pivot our design.

The first iteration of the AdisInsight Patents module was made available to customers on August 31, 2018.  It provided patent information for specific drugs organised in separate Drug Patent Profiles.  Each Drug Patent Profile summarizes the key information from global patents and regional exclusivities protecting that specific drug and presents key information such as patent number, expiry date, claim type and country in easy to read tables allowing users to visualize the protection landscape globally.  Subsequently enhancements were added to AdisInsight Patents to satisfy additional user needs.  Adis Patent Detail Sheets were added to present key information about a specific patent such as title, abstract, inventors, assignee, application number, source, and claim details.  This allowed users to drill down from the Drug Patent Profile to get more information about a specific patent protecting the drug they are investigating.  Later link to the source document at the United States Patent and Trademark Office website or the World Intellectual Property Organization website were added to allow the user to click through to the source patent document.

The intuitive AdisInsight search interface makes identifying patent information easy for users.  The new AdisInsight Patents module utilizes the same familiar search terms such as drug name, indication, mechanism of action, drug class, formulation, location and company used throughout all of the AdisInsight modules.  These powerful search terms are enabled through manual indexing using controlled vocabularies and synonyms.  This produces highly precise search results and minimal noise, especially when compared to free text or Google-like searching.

It has been a very interesting journey. One that ultimately led to a patent product that is proving valuable for our end users as they work to develop better drugs to treat disease.  But this is just the start of the journey we will continue to add more content and more functionality to AdisInsight in the months to come.

Brexanolone (Zulresso™): First Global Approval – First approved therapy for postpartum depression

Brexanolone (Zulresso™): First Global Approval – First approved therapy for postpartum depression

In March 2019, the small molecule brexanolone was approved by the United States Food and Drug Administration (FDA) for the treatment of postpartum depression (PPD) in adult women.[1] Brexanolone, developed by Sage Therapeutics under a license from the University of California, was granted priority review status and breakthrough therapy designation by the FDA.[2][3] Continue reading “Brexanolone (Zulresso™): First Global Approval – First approved therapy for postpartum depression”

Is the Search for a Cure for Alzheimer’s Disease Hopeless?

Is the Search for a Cure for Alzheimer’s Disease Hopeless?

It is likely that in one’s lifetime a friend or family member will be diagnosed with Alzheimer’s disease. As of 2018, approximately 50 million people worldwide are living with dementia and this number is expected to triple to 152 million by 2050.[1]

Despite the increasing prevalence of the disease, no new drugs have been approved for the treatment of Alzheimer’s since 2003.[2] An article recently published on PharmaTimes proclaims, “The search for a cure for Alzheimer’s is far from over.”[3]

Continue reading “Is the Search for a Cure for Alzheimer’s Disease Hopeless?”

Roxadustat (Ai Rui Zhuo® in China): First Global Approval – First-in-class small molecule for anaemia in patients with DD-CKD

Roxadustat (Ai Rui Zhuo® in China): First Global Approval – First-in-class small molecule for anaemia in patients with DD-CKD

In December 2018, roxadustat, developed by FibroGen, in collaboration with Astellas and AstraZeneca, received its first global approval in China for the treatment of anaemia in patients with dialysis-dependent chronic kidney disease (DD-CKD).[1] Roxadustat is expected to launch in China in the second half of 2019.[2]

Continue reading “Roxadustat (Ai Rui Zhuo® in China): First Global Approval – First-in-class small molecule for anaemia in patients with DD-CKD”

Tagraxofusp (Elzonris™): First Global Approval – Breakthrough therapy for BPDCN and novel CD123-targeted therapy

Tagraxofusp (Elzonris™): First Global Approval – Breakthrough therapy for BPDCN and novel CD123-targeted therapy

The recent first global approval of tagraxofusp (Elzonris™) has been reviewed in detail in the First Global Approval report in Adis’ journal Drugs[1], based on the development milestones tracked in AdisInsight[2].

In December 2018, tagraxofusp, developed by Stemline Therapeutics, was approved by the United States Food and Drug Administration (FDA) for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and children 2 years and older.[1][3] Continue reading “Tagraxofusp (Elzonris™): First Global Approval – Breakthrough therapy for BPDCN and novel CD123-targeted therapy”

Avatrombopag (Doptelet®): First Global Approval – Reducing the bleeding risks of invasive procedures in patients with Chronic Liver Disease

Avatrombopag (Doptelet®): First Global Approval – Reducing the bleeding risks of invasive procedures in patients with Chronic Liver Disease

Avatrombopag (Doptelet ®) received its first global approval in the US; this was reviewed in detail in the First Global Approval report in Adis’ journal Drugs[1], based on the development milestones tracked in AdisInsight[2]. Continue reading “Avatrombopag (Doptelet®): First Global Approval – Reducing the bleeding risks of invasive procedures in patients with Chronic Liver Disease”

Erenumab (AIMOVIG™): First Global Approval in US followed by Positive CHMP Opinion – Once-monthly prophylactic approach for adults with Migraine

Erenumab (AIMOVIG™): First Global Approval in US followed by Positive CHMP Opinion – Once-monthly prophylactic approach for adults with Migraine

Erenumab (AIMOVIG™, erenumab-aooe) was launched in the US in July 2018, following its first global approval in the region in May, which was reviewed in detail in the First Global Approval report in Adis’ journal Drugs[1], based on the development milestones tracked in AdisInsight[2]. Also in May 2018, the agent received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP). Continue reading “Erenumab (AIMOVIG™): First Global Approval in US followed by Positive CHMP Opinion – Once-monthly prophylactic approach for adults with Migraine”

Durvalumab (Imfinzi®): CHMP Positive Opinion for NSCLC in Europe

Durvalumab (Imfinzi®): CHMP Positive Opinion for NSCLC in Europe

In July 2018 durvalumab (Imfinzi ®) received a positive opinion from the Committee for Medical Products for Human Use (CHMP). The committee recommended marketing authorisation for the agent in Europe for the treatment of locally-advanced, unresectable non-small cell lung cancer (NSCLC) in adults whose tumours express PD-L1 on ≥1% of tumour cells, and whose disease has not progressed following platinum-based chemotherapy and radiation therapy. [1] Continue reading “Durvalumab (Imfinzi®): CHMP Positive Opinion for NSCLC in Europe”