Takeda gets the pipeline blues

 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.

 Oncology (Ninlaro, Adcetris, Leuplin): $3 759m

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 Ovid-originated rare epilepsy contender soticlestat, to which the Japanese company picked up rights 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	-	-
*Licensed from Ovid; **Partnered with Arrowhead & sales attributed to Arrowhead; ^Partnered with Neurocrine; ^Partnered with Xoma. Source: Evaluate Pharma & clinicaltrials.gov. https://www.evaluate.com/vantage/articles/news/trial-results/takeda-gets-pipeline-blues