The European Union endorsed the third vaccine targeting COVID-19 on an emergency basis. Now, AstraZeneca’s AZD1222, originally developed by the University of Oxford, was given conditional approval right after regulators suggested the greenlight. The EU nations face a growing crisis in the middle of the cold season wave of the pandemic and production-based delays with other vaccines, including the one made by BioNTech and Pfizer. The crisis is now fed by the emergent three mutants from the UK, South African and Brazil. Authorized or emergency use in the UK since earlier in the month as well as in India, in partnership with the Serum Institute of India, the pressure is on as European Commission President Ursula von der Leyen recently declared, “I expect the company to deliver the 400 million doses as agree.” Tension mounts over in Europe as TrialSite recently noted powerful bureaucrats and ministers in places like Italy eye breach of contract messaging should product now materialize soon. In TrialSite’s “We are all in Big Trouble if Pharma can’t get its Act Together and Deliver Vaccine Product,” the expectation was that with large injections of taxpayer capital that pharma companies were capable of delivering the goods. It’s, of course, one thing to use brilliantly advanced life science technology such as messenger RNA to accelerate vaccines and another to organize the firm to deliver on a global, unprecedented, massive scale. Pfizer now smartly makes the moves to do this by inking partnerships with both Sanofi and Novartis. But what did the New York City-based firm miscalculate? While some controversy marked AstraZeneca’s path to authorization, the overall efficacy rate can help. TrialSite introduces what some would consider controversial ideas for the pharma industry, government and regulators under “what to do?” below.
The AZD1222 Vaccine
Again developed by a brilliant team in the UK, the virus derives from the adenovirus family and involves the SARS-CoV-2 spike protein gene, the unique-looking crown-like studs that makes this virus so dangerous—so transmissible—allowing it to penetrate cells and trigger host infection. Once AZD1222 (ChAdOx1 nCoV-19) is injected into the human host, the cells use the gene to produce the spike protein, and of course, this elicits an immune system response that offers the human host more protection against SARS-CoV-2. A majority of the study participants’ ages have ranged from 18 to 55, hence the possibility that the EU may set a ceiling on participating age at 55.
Controversies Followed this Vaccine Candidate
That the company (AstraZeneca) has experienced some controversy around the development of this vaccine is an understatement. TrialSite early on identified a strange anomaly—after chatter in August in the Financial Times that the previous POTUS was eying this particular vaccine as an election day surprise, TrialSite was the only media platform to report an “Unprecedented Compression of Timeline of Estimated Start Date to Estimated Primary Completion Date.” An unheard of compression of duration for a Phase 3 vaccine trial between the estimated trial start date and estimated primary completion date of just 3.5 months raised a few eyebrows.
Thankfully, the general results are looking promising for AZD1222; however, the company has received notable criticism over a number of actions, for example, how they collated and presented interim results for the third and final phase of the trials involving AZD1222. An “open letter to AstraZeneca’s CEO on transparency” was published in the prominent Boston-based online publication STAT, concerning the glaring transparency gaps upon the reporting of a couple of adverse events in the UK.
A similar situation surfaced in India where the Serum Institute of India (SII), the largest vaccine producer in the world as measured by volume, inked a deal with AstraZeneca to develop and supply the “Oxford” vaccine for the world’s second most populated nation. During the study, a volunteer became severely ill ten days after a jab. The treating hospital (where the study occurred) produced a rapid diagnosis, assuring no connection to the study investigational candidate, yet there was no accompanying documented evidence available for the public to review.
A lawsuit commenced, followed by what many would consider an over-the-top ruthless response by SII. They threatened to essentially sue the volunteer out of economic existence. Indian consumer activism groups expressed to their groups a letter from the All India Drug Action Network. Was this volunteer just a troublemaker or was there something else going on here? Was the SII attempting to intimidate an individual volunteer? The SII thereafter strongly suggested the government waive all liability. Pharma companies in the U.S. had no worries due to the Public Readiness and Emergency Preparedness Act.
What to Do?
With production and supply challenges right at the wrong time, we mentioned earlier, Pfizer smartly made moves to partner up with Novartis and Sanofi to augment production and get on top of this supply crisis. But what about the other Big Pharma makers? Merck recently threw in the towel on their vaccine. Why not pair up Merck with Moderna to enter a similar deal like Pfizer, Sanofi and Novartis? Lots of taxpayer money has been handed out. The Defense Production Act is a formidable tool to compel parties to do the right thing. What about other U.S. vaccine makers that are further back in their efforts?
What about the J&J (Janssen) vaccine and their single-shot viral vector vaccine? While it has lower efficacy than the mRNA-based products, it could be a stand-in on an emergency basis in Europe for those who won’t receive an mRNA-based vaccine for months. Perhaps this could introduce intermediate level protection?
What about the Novavax preliminary results revealing an 89.3% efficacy? Could this not be accelerated? Other ideas sent into the TrialSite from very insightful readers suggest studying the UK approach, where they allow the time gap between doses to extend to 12 weeks. This offers protection to double the population in an accelerated manner. Of course, the counter goes that there just isn’t sufficient data to support such action from trials, but what is the probability that immunity would wane in that time frame since it’s not observed in natural immunity? Not an ideal situation, but the impending risk of more escape of far more dangerous, more transmissible mutant variants raises the alarm for action.
The FDA should publish clear approval guidelines for the variant boosters. These guidelines should detail the requirements for a variant booster to be included in the original Emergency Use Authorization (EUA) without the requirement of additional trials.
The NIH and FDA also have to move on repurposed drugs such as Ivermectin, identifying risk versus benefits and accept mounting clinical data as well as Real World Evidence (RWE) as the basis of these emergency evaluations. A low-cost, generic that inhibits transmission, duration of illness and other benefits with a well-known safety profile could be a powerful support tool along with vaccination and other emerging treatments.
Finally, the new POTUS has elicited the Defense Production Act to possibly accelerate pandemic defenses—they can start with mass production of N95 masks and offer them at no cost to every positive COVID-19 patient. These should be offered to the public at no-or-low cost. The reality is that cloth masks aren’t sufficient to stop the spread of the pathogen. N95s have shown to be highly effective in preventing the transmission of SARS-CoV-2.
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