Friday Five – The pharma week in review (19 March 2021)

AstraZeneca’s COVID-19 vaccine caught in new firestorm

A number of major European countries announced this week that they have temporarily paused use of the COVID-19 vaccine developed by AstraZeneca and the University of Oxford, amid reports it has been linked to an increased risk of rare thrombotic events. Both the World Health Organisation and the European Medicines Agency continue to support use of the vaccine saying its benefits outweigh any safety risks.

The decision to pause use of the vaccine has proven controversial, not only as it occurs against the backdrop of a continued dispute between the European Union, AstraZeneca and the UK about supply shortfalls, but also as COVID case numbers continue to increase sharply across mainland Europe.

At odds with this consternation and scrutiny, the vaccine appears to be playing a pivotal role in significantly reducing hospitalisations and deaths in the UK. So what gives?

If there is any credibility issue, its developers cannot be absolved of all blame. Initial clinical data was both messy and less impressive than the mRNA vaccines developed by BioNTech/Pfizer and Moderna. But equally, if not more, damaging has been subsequent politicisation of the AstraZeneca vaccine in Europe against the backdrop of Brexit.

UK politicians were initially keen to stoke this fire and the European Union, increasingly flustered by shortfalls in its own vaccine procurement programme, took the bait. Which makes this week’s safety concerns all the more difficult to judge objectively.  

Ongoing scrutiny of the vaccine’s real-world safety profile should certainly not be de-emphasised or overlooked in the midst of a pandemic, but many experts have struggled to separate a temporary suspension of the vaccine’s use in numerous European countries from the bloc’s political posturing. More so as both the EMA and WHO continue to believe the vaccine’s benefits far outweigh any safety risks.

With COVID-19 cases rising sharply again across mainland Europe and with vaccine hesitancy already prevalent in some countries such as France, continued politicisation of the AstraZeneca vaccine could have both profound short and long-term implications for the region.

Eli Lilly switches to the road less travelled with donanemab

On the back of updated results for its investigational Alzheimer’s disease drug donanemab, Eli Lilly mapped out a potential route to approval in a conference call with investors earlier this week.

Among the most intriguing elements of Eli Lilly’s clinical strategy are changes being implementing to the ongoing TRAILBLAZER-ALZ 2 study, which was launched last summer.

The company said it plans to expand enrolment to 1,000 patients from 500 and focus the primary analysis on those with intermediate or lower tau levels based on findings from TRAILBLAZER-ALZ suggesting that this population benefited the most from therapy.

In addition, the company is also reclassifying it as a Phase III trial and changing the primary endpoint to iADRS from Clinical Dementia Rating Scale Sum of Boxes (CDR-SB).

Switching from CDR-SB, which has traditionally been the FDA’s preferred primary endpoint of choice, to iADRS may be the most intriguing move of all. Eli Lilly made the case on its webcast that the former measure is less consistent, though there is little precedent for use of iADRS as a registrational endpoint, which will inevitably make investors nervous.

Unsurprisingly, Eli Lilly was pressed by investors about whether they have received buy-in on iADRS from US regulators but management was cautious with its answers, acknowledging it is risky to use a novel endpoint while expressing confidence that it is an appropriate measure. The company also emphasised that TRAILBLAZER-ALZ 2 is now highly powered to demonstrate a positive result.

Gilead, Merck announce HIV collaboration

ViiV Healthcare got the jump on the long-acting HIV market, but Gilead Sciences and Merck & Co. are hoping to fight back by combining forces, which they hope will significantly improve their competitiveness and shorten the path to market.

Whether recent US approval for ViiV’s Cabenuva lit a fire under Gilead and Merck is open to speculation, but either way the companies entered into a marriage of convenience on March 15, with a goal of combining their respective lenacapavir (capsid inhibitor) and islatravir (NRTI) to create long-acting HIV candidates.

More on the deal here

Furthermore, in a note to investors published on Tuesday, analysts at Jefferies wrote that following discussion with a key opinion leader (KOL) they have learnt of growing interest in long-acting HIV therapies, which has accelerated following US approval of ViiV Healthcare’s Cabenuva in January.

This feedback supports results from our short survey fielded to US HIV specialists last month. Our survey indicates that Cabenuva is viewed as a highly innovative addition to the treatment landscape which could significantly reduce the psychological burden on a sizeable proportion of HIV patients.

More here

Rinvoq approval delayed by FDA’s JAK assessment

AbbVie said Wednesday that the FDA is prolonging its review of a marketing application seeking to expand Rinvoq's label to include adults with active psoriatic arthritis. The three-month delay means the agency is now expected to decide on the filing for the once-daily oral JAK inhibitor late in the second quarter.

According to AbbVie, the FDA recently asked to see an updated assessment of the benefit-risk profile for Rinvoq in the psoriatic arthritis indication. Separately, AbbVie said it received a similar request from the FDA related to a marketing application for Rinvoq in atopic dermatitis, and that it plans to submit a response "shortly."

The FDA’s request for an additional benefit/risk assessment of Rinvoq for these two indications would appear to be a consequence of safety concerns about the JAK inhibitor class, which have been raised by new data for Pfizer’s drug Xeljanz showing association with an increased risk of major cardiovascular events and malignancies.

Whilst the FDA is unlikely to withdraw Xeljanz from the market, other JAK inhibitors could be viewed as ‘guilty by association’ despite manufacturer claims of greater selectively (and thus few ‘off target’ effects) an expert told FirstWord recently. Onus will be on companies like AbbVie to demonstrate their agents are safer, the KOL added.

Our recent survey of 100 rheumatologists indicates that class-associated safety concerns emanating from Xeljanz could have a particularly notable effect in the US market, partly as Pfizer’s drug is widely used here but more sparingly in European markets.

More US rheumatologists – about 50% of those we surveyed – say they are very or extremely concerned about the new safety disclosures for Xeljanz and feedback suggests this could dampen future growth prospects for Rinvoq.

More analysis here

FTC launches task force to scrutinise pharma M&A deals more closely

The US Federal Trade Commission (FTC) on Tuesday announced the formation of a working group, in collaboration with competition regulators in the EU, UK and Canada, to update how they review buyouts in the pharmaceutical industry amid concerns such deals may drive up drug prices or stifle innovation. Rebecca Kelly Slaughter, acting chair of the FTC, said "we intend to take an aggressive approach to tackling anticompetitive pharmaceutical mergers."

Slaughter noted that "given the high volume of pharmaceutical mergers in recent years, amid skyrocketing drug prices and ongoing concerns about anticompetitive conduct in the industry, it is imperative that we rethink our approach."

In a Twitter thread on Tuesday, Slaughter suggested that the FTC's longstanding practice with respect to deals in the pharmaceutical industry has been too narrow, focusing mainly on the angle of product and pipeline overlap between merging parties – something she says "does not capture all the effects of these deals." 

The FTC also said the impact of pharmaceutical mergers was not "just about the respective size of the two companies,” suggesting that smaller acquisitions will also be scrutinised more closely.

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