Friday Five – The Pharma Week in Review (15 October 2021)

One step forward, two steps back for allogeneic CAR-Ts

Off-the-shelf CAR-T therapies remain a potentially compelling proposition but updates from Allogene and CRISPR Therapeutics during the past week suggest they have a long way to go.

Allogene has cast a shadow of uncertainty over the field by announcing that its entire pipeline has been put on clinical hold by the FDA following identification of chromosomal abnormalities in one study patient treated for lymphoma. Details are scarce but the clinical hold has prompted concerns that gene editing – or at least the TALEN platform used by Allogene – could be to blame.

Elsewhere, new data unveiled this week for CRISPR’s investigational lymphoma therapy CTX110 are ostensibly positive in terms of impressive enough response rates and acceptable toxicity but simultaneously raise question marks about the durability of allogeneic CAR-T treatments, with management conceding that subsequent re-dosing of relapsed patients may be a necessity.

Verzenio approved for early-line breast cancer

Eli Lilly has scored a major endorsement in its bid to differentiate the breast cancer treatment Verzenio from other drugs in the CDK4/6 inhibitor class, by securing US approval to treat certain patients with early stage HR-positive, HER2-negative disease who are at a higher risk of recurrence.

This potentially opens up a significant new commercial opportunity for Lilly, albeit one that will require some navigation on the company’s part. Until overall survival data for Verzenio is mature and supports broader approval in the adjuvant setting, use of the drug has been limited by the FDA to patients with a Ki-67 score of ≥20%.

This biomarker has not typically been used in the past to determine treatment decisions, the company concedes, and will require a shift in physician behaviour. On a more positive note approval of Verzenio as an adjuvant therapy is likely to fuel its momentum as the most upwardly mobile drug in class, our feedback from oncologists suggests.

More executive change at J&J

Paul Stoffels will retire from his role as Johnson & Johnson’s chief scientific officer at the end of 2021 after a decade in the role, it was announced this week.

Stoffels was responsible for establishing the Johnson & Johnson Innovation unit in 2013 and has overseen a productive period for the company’s R&D pipeline when measured by novel drug launches and external collaborations.

Blockbuster drug approvals under his tenure include Darzalex (multiple myeloma), Stelara (various inflammatory conditions) and Tremfya (psoriasis). Johnson & Johnson was also responsible for developing a first-generation COVID-19 vaccine, albeit one which has been used less widely than expected due to safety concerns and manufacturing issues.

No replacement for Stoffels has been announced. Alex Gorsky will also retire as CEO at the end of the year to be succeeded by Joaquin Duato.

Dupixent competitors need to show more, says expert

Excitement around novel drugs targeting OX40 as potential new therapies for moderate-to-severe atopic dermatitis has been amplified by initial data from agents being developed by Amgen and Sanofi, presented at the recent EADV meeting.

However, one expert FirstWord spoke to this week preached caution and said the efficacy demonstrated by anti-OX40 mAbs is not as compelling as Sanofi and Regeneron’s IL-4/IL-13 inhibitor Dupixent. Furthermore, Dupixent arguably performs better in the real-world than it did in clinical studies, notes the KOL.

This is good news for Sanofi and Regeneron, who anticipate peak annual sales for Dupixent of around $10 billion, but no doubt provides further frustration for JAK inhibitor developers.

Our KOL noted that in comparison to emerging anti-OX40 drugs, oral JAKs offer impressive efficacy arguably superior to Dupixent but are likely to be hamstrung by safety warnings.

Furthermore, he described recent FDA inclusion of a boxed warning on Incyte’s newly approved topical JAK Opzelura as “heinous” and suggestive of the agency taking a hard-line approach to the orals. 

FDA stance on AAs gets thumbs up from physicians

Our new snap-poll of 46 US oncologists suggests that most agree FDA labelling for drugs with accelerated approval should be updated to reflect the results of confirmatory trials, with indications withdrawn for those that fail to demonstrate a clinical benefit post-approval.

The poll comes ahead of a December 2 meeting of the FDA’s oncologic drugs advisory committee (ODAC) to review accelerated approvals for two drugs that have been on the market for more than five years but have yet to report confirmatory trial outcomes. A handful of immunotherapies have also been voluntarily withdrawn for use in certain indications by their manufacturers following discussion with the agency over the course of 2021.

Findings from our poll indicate that 80% of oncologists are somewhat or very satisfied with the agency’s standards for accelerated approval of cancer drugs, and strongly or somewhat agree that surrogate endpoints for cancer therapies reasonably predict clinical benefit.

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