Takeda gets the pipeline blues

A big selloff on a mid-stage stumble seems harsh, but Takeda has problems on the horizon.

Trial Results

Takeda’s 11% or $3.3bn loss in value yesterday, owing to the halt of the phase 2 narcolepsy project TAK-994 on a toxicity signal, seemed overdone. However, a look at the company’s pipeline shows that TAK-994 had relatively high hopes attached, and it is hard to get excited about some of the other contenders.

The stumble comes hot on the heels of the failure of pevonedistat, which had been another key component of Takeda’s R&D engine. The Japanese group will only come under more pressure to replace its biggest seller, Entyvio, as that drug’s 2026 patent expiry creeps closer, and the latest setbacks will have dented confidence in its strategy.

A more pressing problem is the loss of exclusivity for the ADHD drug Vyvanse in 2023. Perhaps Takeda will make a foray into M&A to restock its pipeline, and now might be a good time with valuations lower than they have been in recent years.

Takeda has plenty of R&D projects, the table below shows. The issue might be quantity over quality, sellside consensus sales forecasts compiled by Evaluate Pharma suggest.

It looks unlikely that the oral orexin agonist TAK-994 will be part of Takeda’s future, although the group did not give details on the issue that spurred it to stop two phase 2 trials.

The toxicity signal also raises doubts about the company’s two other orexin agonists, TAK-861 and TAK-925. The only other group with clinical-stage assets that act on this target, according to Evaluate Pharma, is NLS Pharmaceutics, whose extended-release formulation of mazindol is in phase 2 for narcolepsy.

If TAK-861 and TAK-925 also fall by the wayside, Takeda’s neuroscience pipeline will look sparse. Other assets here include the rare epilepsy contender soticlestat, to which the Japanese company gained full rights from Ovid this year, TAK-071 in Parkinson’s, and earlier-stage projects in Parkinson’s and depression.

Most valuable

According to the sellside, the group’s most valuable project by 2026 revenues is the dengue vaccine TAK-003, which is due an EU CHMP opinion by the end of the year. The jab is expected to eclipse Sanofi’s FDA-approved dengue vaccine Dengvaxia, but there have been concerns about waning efficacy with TAK-003. And a tropical disease vaccine is never going to be a huge money spinner.

Takeda is offloading another vaccine candidate, the norovirus shot TAK-214, to a new joint venture known as Hillevax.

Meanwhile, the Arrowhead-partnered hep B asset ARO-AAT/TAK-999 has shown promise in alpha-1 antitrypsin deficiency, but it is still early days.

In oncology, hopes are high for the Car-NK cell therapy project TAK-007; however, this field is growing crowded. Takeda’s other mid-stage cancer candidates are the T-cell engager TAK-186, gained via the buyout of Maverick Therapeutics, and TAK-981, a Sumo inhibitor – Takeda appears to be the only group targeting this mechanism.

True, Takeda has just bagged approval for Exkivity in EGFR exon 20 insertion-positive NSCLC, but this is a niche use and the drug is only expected to bring in $436m by 2026.

With so many irons in the fire, it might not be time for Takeda to panic just yet. But the pipeline needs to start delivering results soon.

Takeda's mid-to-late-stage pipeline
Product Description Status 2026e sales ($m) NPV ($m)
Filed
TAK-003 Dengue virus vaccine Filed in EU; US filing due H2 2021 531 1,455
Maribavir (TAK-620) CMV protein kinase inhibitor for post-transplant CMV infection Filed in US & EU 354 1,118
Eohilia (TAK-721) Topical corticosteroid for eosinophilic oesophagitis April Pdufa date missed 187 293
Phase 3
TAK-755 Adam-13 replacement therapy for bleeding disorders Ph2 Soar-HI data in immune-mediated TTP due 2021; ph3 data in congenital TTP due 2022 265 1,012
TAK-609 Intrathecal formulation of Elaprase for Hunter syndrome US filing due H2 2021 73 104
Soticlestat (TAK-935) Cholesterol 24-hydroxylase inhibitor for rare epilepsies Ph3 in Lennox-Gastaut syndrome & Dravet syndrome not yet recruiting 59 165
Phase 2
TAK-999 (ARO-AAT)* Alpha-1 antitrypsin RNAi project Ph2 Sequoia in alpha-1 antitrypsin deficiency 247 1,739
TAK-994 Orexin 2 receptor agonist for narcolepsy Ph2 terminated on toxicity signal 389 1,657
TAK-214 (HIL-214) Norovirus vaccine Ph2 ongoing; Takeda forming HilleVax, JV with Frazier Healthcare Partners, to commercialise 273 1,004
TAK-007 Anti-CD19 CAR-NK cell therapy Ph2 in r/r NHL not yet recruiting 266 1,163
TAK-611 Arylsulphatase A stimulant Ph2 Embolden in metachromatic leukodystrophy 55 184
TAK-607 Growth hormone for complications of prematurity Pedal in retinopathy & NCT03253263 in lung disease 3 1
TAK-041** G protein-coupled receptor 139 agonist  Ph2 completed in anhedonia in depression - -
TAK-071 Muscarinic M1 receptor positive allosteric regulator Ph2 in Parkinson's - -
TAK-186 (MVC-101) T-cell engager Ph1/2 in solid tumours - -
TAK-981 Sumo inhibitor Ph1/2 in various cancers including NHL - -
Mezagitamab (TAK-079)^ Lymphocyte differentiation antigen CD38 antibody Ph2 in immune thrombocytopenia & myasthenia gravis - -
Sibofimloc (TAK-018/EB8018) Bacterial fimbrial adhesin inhibitor Ph2 in Crohn's - -
TAK-101 Gliadin desensitiser Ph2 in coeliac disease - -
TAK-906 Dopamine D2 & D3 receptor antagonist Ph2 completed in gastroparesis - -
TAK-951 Peptide agonist Ph2 in post-operative nausea & vomiting - -
TAK-954 5-HT4 receptor agonist Ph2 in postoperative gastrointestinal dysfunction - -
*Partnered with Arrowhead & sales attributed to Arrowhead; **Partnered with Neurocrine; ^Partnered with Xoma. Source: Evaluate Pharma & clinicaltrials.gov.

This story has been updated to clarify the origins of soticlestat.

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