Go or no go? Lilly’s valuable diabetes contender

Tirzepatide heads for its first FDA approval and Enhertu eyes an earlier setting, as Verrica and Axsome keep their fingers crossed.

May could see one of the most valuable approvals of the year: that of Lilly’s tirzepatide in diabetes. A precise Pdufa date has not been disclosed but the deadline is looming, and Lilly is gunning for a slice of Novo Nordisk’s share of this market. 

Elsewhere, Astrazeneca and Daiichi Sankyo’s Enhertu looks set to move into second-line breast cancer. And Verrica and Axsome are hoping for better outcomes after previous setbacks for VP-102 and AXS-05 respectively. 

Big bucks 

Approval is expected for Lilly’s tirzepatide in type 2 diabetes, after the GLP-1/GIP dual agonist scored in five pivotal trials showing statistically significant HbA1c (blood sugar) reductions and weight loss.  

The project has also demonstrated cardiovascular safety – a meta-analysis of the Surpass programme found a 19% relative risk reduction in major cardiovascular events with tirzepatide versus pooled comparator data. A large cardiovascular outcome trial versus Lilly’s own Trulicity is ongoing. 

Cross-trial comparisons point to fierce competition for Novo Nordisk's flagship GLP-1, Ozempic, with tirzepatide displaying stronger efficacy and little additional toxicity. Still, Novo's lead is important, with Ozempic set to remain the market leader in type 2 diabetes by 2026, according to Evaluate Pharma's sellside numbers.   

Diabetes is only the beginning of the road for tirzepatide, which scored in obesity this week, while trials in Nash and heart failure with preserved ejection fraction are ongoing.  

Novo leads in type 2 diabetes
Product Company Mechanism of action Admin route Indication sales ($bn)
2022e 2026e
Ozempic (semaglutide) Novo Nordisk GLP-1 receptor agonist Injection 6.4 9.0
Trulicity Lilly GLP-1 receptor agonist Injection 7.2 6.2
Tirzepatide Lilly GLP-1/GIP dual agonist Injection 0.1 5.4
Rybelsus (semaglutide) Novo Nordisk GLP-1 receptor agonist Oral 1.5 4.9
Jardiance Boehringer Ingelheim SGLT2 inhibitor Oral 3.6 4.9
Source: Evaluate Pharma.

Label expansion 

Astra and Daiichi’s Enhertu looks set for approval in second-line Her2-positive breast cancer. Data at last year’s Esmo showed a highly significant 72% reduction in risk of progression versus Roche’s rival antibody-drug conjugate Kadcyla in the Destiny-Breast03 study. 

The partners need Enhertu’s well-known toxicity, interstitial lung disease (ILD), to be kept under control if the drug is to sell well in early treatment lines. Education of physicians is ongoing, and rates of ILD seem to be coming down in clinical trials. In Destiny-Breast03 ILD was seen in 10.5% of patients given Enhertu, versus 1.9% with Kadcyla. This was an improvement on earlier studies, with most of the Enhertu cases grade 1 or 2. 

Enhertu is approved in third-line disease under the accelerated pathway, and the confirmatory study Destiny-Breast02 is to report in the second half of the year. Subsequent approvals this year could come in Her2-low breast cancer, following success in Destiny-Breast04, on which filings are due before mid-year, and in Her2-mutated lung cancer, which is already under review.  

And finally 

Two decisions expected soon come after prior setbacks, namely those for Verrica’s VP-102 and Axsome’s AXS-05.  

The latter, for major depressive disorder, missed its Pdufa date last August after the FDA issued a CMC-related deficiency letter, causing Axsome’s shares to plummet 46%. And the company announced this week it is expecting a knockback for another of its products, AXS-07 for migraine, also on CMC problems.

Hopefully the AXS-05 issues are over. Axsome announced earlier this month that it had received and agreed to post-marketing requirements for the depression therapy, with FDA action now anticipated this quarter. 

For Verrica it will need to be third time lucky for VP-102, after two previous knockbacks.  

Initially the product, which will be called Ycanth if approved, received a CRL in 2020 owing to CMC-related requests. The second knockback a year later was due to quality issues at a contract manufacturer. 

VP-102, a formulation of cantharidin delivered via a single-use applicator, is intended to treat molluscum contagiosum, a common infectious skin disease, and VP-102 is Verrica’s lead product. Verrica desperately needs a win as it is light on cash. The company says its current reserves of just $70m are enough to support operations into the third quarter.  

The tables below lists first-time and supplementary US approval decisions due next month, with consensus forecasts from Evaluate Pharma

Notable first-time US approval decisions due in May
Project Company Pdufa date Indication(s) 2026e sales by indication (SBI) ($m) Note
Vonoprazan (dual and triple therapy) Phathom May 3 Adults with H pylori infection - Phathom in-licensed US, European, and Canadian rights to vonoprazan (Takecab) from Takeda
MT-1186 (oral edaravone) Mitsubishi Tanabe May 12 ALS - Oral version of Radicava (intravenous infusion)
VP-102 Verrica May 24 Molluscum contagiosum 251 See text
Miglustat Amicus May 29 Pompe disease 169* Part of AT-GAA a two-component therapy with cipaglucosidase, Pdufa for second part in July
Tirzepatide Lilly Q2 Type 2 diabetes 5,441 See text
Tapinarof Dermavant Q2 Plaque psoriasis - -
AXS-05 Axsome Q2 Major depressive disorder 582 See text
Bimzelx UCB H1 Plaque psoriasis 953 Decision delayed in Oct owing to Covid travel restrictions
Annik (penpulimab) Akeso/Sino Est H1 3L nasopharyngeal carcinoma - Go or no go? Bristol's first-in-class hopes
*Forecasts for AT-GAA. Source: Evaluate Pharma & company releases.
Supplementary and other notable approval decisions due in May
Product Company Indication (clinical trial) Date
Tyvaso DPI Mannkind/ United Therapeutics PAH and pulmonary hypertension associated interstitial lung disease  May (resubmitted, previous CRL)
Myfembree Pfizer/ Myovant Moderate to severe pain associated with endometriosis (Spirit 1, Spirit 2) May 6 (delay likely as deficiencies noted)
Evrysdi Roche/ PTC Pre-symptomatic infants under 2 months old with spinal muscular atrophy (Rainbowfish) Estimated May 25
Opdivo + Yervoy, Opdivo + chemo Bristol Myers Squibb 1L unresected advanced, recurrent or metastatic oesophageal squamous cell carcinoma (Checkmate-648) May 28
Enhertu Astra/Daiichi Her2+ve breast cancer after anti-Her2-therapy (Destiny-Breast 03) Q2
Olumiant Lilly Treatment of certain hospitalized patients with Covid Q2 (already has EUA)
Kymriah Novartis 3L FL (Ph2 Elara) Pending
Source: Evaluate Pharma & company releases.

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