Friday Five – The Pharma Week in Review (2 July 2021)

Listen to FirstWord Pharma PLUS editors Becky Simon, Michael Flanagan and Simon King discuss these stories on the lastest edition of The First Take podcast - on apple podcastsSpotify or Google  

Sanofi goes bigger on mRNA vaccines 

Having publicly skirted around the issue of whether mRNA could upend the broader vaccine market (on the back of the integral role this technology has played in the development of COVID-19 vaccines) Sanofi has decided that the fear of missing out is too great.

On Tuesday it announced plans to establish an mRNA vaccine centre of excellence which will be funded to the tune of €400 million a year and employ around 400 staff. This will build on the work Sanofi is already undertaking with Translate Bio and it hopes to have six mRNA vaccine candidates in the clinic by 2025.

Rivals Moderna and Pfizer, who have led the way in mRNA COVID-19 vaccine development, have previously unveiled their own long-term plans to move the technology into other segments of the vaccine market.

See ViewPoints: Sanofi takes its mRNA aspirations up a notch

Could CAR-T move upstream? 

Use of CAR-T therapies to treat certain haematological cancers has so far been limited to the salvage setting but data continues to accumulate suggesting that use in earlier-stage patients has considerable clinical merit.

This week Gilead shared positive top-line Phase III data for its CAR-T therapy Yescarta as a second-line treatment for patients with large B-cell lymphoma (LBCL). 

In the ZUMA-7 study, Yescarta demonstrated a 60% improvement against the primary endpoint of event-free survival (EFS) versus current standard of care, which comprises chemotherapy and stem cell transplant. Bristol Myers Squibb also recently announced similarly positive top-line data, albeit from a smaller study.

See ViewPoints: CAR-T battle heats up for Gilead, BMS

Approval of CAR-T therapies for use in earlier-stage patients would theoretically open up the size of the addressable market for these agents, though multiple commercialisation challenges persist for this treatment modality; explaining why investment continues to be channelled into development of potentially more convenient allogeneic CAR-T products.  

The JAK waiting game continues 

With multiple Big Pharma companies having invested considerable sums of money into developing JAK inhibitor drugs for a raft of potential indications, the FDA’s ongoing investigation into the safety of Pfizer’s Xeljanz – an older, first-in-class JAK – continues to cast a shadow of uncertainty over a number of large-cap names.

None more so than AbbVie which is hoping to generate significant future revenues from Rinvoq, a JAK inhibitor designed to be more selective – and thus cleaner from a safety perspective – than older drugs in the class such as Xeljanz. 

This week, AbbVie confirmed that a number of pending regulatory decisions from the FDA will be delayed including Rinvoq’s potential approvals in the US as a treatment for psoriatic arthritis and ankylosing spondylitis. A further decision regarding potential use in atopic dermatitis scheduled for next month is also expected to be postponed.

AbbVie can take some solace in the fact that late last week the European Medicines Agency (EMA) recommended Rinvoq be approved for atopic dermatitis. Furthermore, the European regulator has already approved the JAK inhibitor for psoriatic arthritis and ankylosing spondylitis.

In addition, positive efficacy data continues to accumulate for Rinvoq, most recently this week as a treatment for ulcerative colitis, reinforcing the view that if AbbVie’s drug can keep its distance from safety concerns it will be a major seller for the company.

ICER prescribes little leeway on Aduhelm cost effectiveness

Biogen has previously said it could consider lowering the price of its controversial Alzheimer’s disease drug Aduhelm, but only if it is used more widely than the company expects.

These comments have done little to placate those who have scrutinised the cost versus potential benefit of Aduhelm, including the Institute for Clinical and Economic Review (ICER) which issued a revised cost effectiveness report this week estimating the drug should be priced between $3000 and $8400 annually for patients with early Alzheimer's disease in order to be cost-effective. 

This range works out at an 85% to 95% discount from the $56,000 price tag that Biogen and its partner Eisai have set for the anti-amyloid antibody, an amount ICER considers to be "not in reasonable alignment with its clinical benefits, even under a scenario with optimistic assumptions regarding…effectiveness."

Intellia sets gene editing precedent

Intellia Therapeutics secured a ‘first’ in the field of CRISPR gene editing, where results from a small study demonstrated proof-of-concept for in vivo gene editing- potentially opening the door to broad new applications for the genetic technology.

Intellia’s NLTA-2001 programme treated six patients with hereditary transthyretin amyloidosis (ATTR), with all six showing reductions in plasma transthyretin levels indicative of successful knockdown of the faulty gene. However, follow-up is currently limited to 28 days for the potentially one-time, curative treatment, with only a small number of patients treated.

But the results demonstrate that Intellia has cracked one of the key limitations of genetic technologies- efficient delivery to target tissues- while also demonstrating no acute safety risks, despite long-standing concern over immunogenic reactions and off-target editing. The liver is the low-hanging fruit in terms of drug delivery, and Intellia’s next Cas9 clinical programme will target the same tissue to treat a different disease.

Additional follow-up from Intellia’s CRISPR candidate is expected in the second half, where analysts will be watching for indicators of durability for the gene knockdown in the Phase I study, as well as a deeper look at potential off-target edits.

See ViewPoints: Patience pays off at Intellia

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