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  1. Analysis
October 25, 2021

Regulatory roundup: BMS’s deucravacitinib dives in ulcerative colitis after Phase II fail

AstraZeneca’s Imfinzi in hepatocellular carcinoma and GlaxoSmithKline in parasitic disease are among other assets reviewed by GlobalData’s Investigative News team.

By Reynald Castañeda

Need to know:

GlobalData’s Investigative News team reviews data generated by an in-house model that combines machine learning and its proprietary algorithm. Likelihood of Approval (LoA) provides the probability of a drug in securing market authorization; Phase Transition Success Rate (PTSR) indicates the probability of a drug advancing to the next stage of development. The model uses data points from individual drugs, clinical trials, regulatory milestones, company, and financial databases.

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BMS’s TYK2 inhibitor suffers UC setback

Bristol Myers Squibb’s deucravacitinib suffered a setback to its potential to move to the next development stage in ulcerative colitis (UC) after its Phase II study did not meet its primary endpoint. Deucravacitinib’s PTSR dropped by 20 points to 16% after BMS announced trial results on 8 October. The PTSR change occurred on 11 October.

The Phase II study (NCT03934216) compared the oral tyrosine kinase 2 (TYK2) inhibitor deucravacitinib to placebo in patients with moderate-to-severe UC. The trial did not meet the primary endpoint of the proportion of patients who achieved clinical remission at 12 weeks. It also failed in achieving the secondary endpoints that measured efficacy through histological or endoscopic measurements, among other outcomes.

Following the Phase II update, deucravacitinib’s LoA in UC also dropped to 14% with an eight-point decrease. BMS said it will continue to develop deucravacitinib in inflammatory bowel disease and other indications like lupus, psoriatic arthritis, and other immune-mediated diseases. The company is aiming at a greater than $4bn nonrisk adjusted revenue target for deucravacitinib in 2029, the 10 October release states.

AstraZeneca reports Phase III HCC data

AstraZeneca’s Imfinzi (durvalumab) saw its LoA jump ten points to 42% in first-line hepatocellular carcinoma (HCC) following positive Phase III results.

In the Phase III HIMALAYA trial (NCT03298451), Imfinzi, in combination with AstraZeneca’s own tremelimumab, met the primary endpoint of noninferiority in overall survival (OS) versus Bayer’s Nexavar (sorafenib), according to a 15 October press release. The LoA was updated on 19 October. Imfinzi monotherapy had numeric, but not statistically significant, noninferiority OS versus Nexavar.

The company said full data from HIMALAYA will be presented at a future medical meeting. Imfinzi is an anti-PDL1 monoclonal antibody (mAb); tremelimumab is also a mAb but targets CTLA-4. Imfinzi is marketed in the US to treat lung cancer. On 22 February, AstraZeneca withdrew it accelerated approval for Imfinzi in bladder cancer.

GSK asset stumbles in parasitic disease

GlaxoSmithKline’s leishmaniasis candidate GSK-3494245 saw its PTSR drop after its Phase I trial in healthy volunteers was suspended. The PTSR fell by 28 points to 32%. Leishmaniasis is a parasitic disease caused by female phlebotomine sand flies. GSK-3494245 inhibits chymotrypsin-like activity caused by the parasites.

The Phase I double-blind study (NCT04504435) was suspended when an adverse event that met protocol-defined stopping criteria was observed in a single participant, as per an 18 October update on ClinicalTrials.gov. GlobalData had its latest update on 19 October.

The study was designed to judge GSK-3494245’s safety and tolerability in healthy volunteers. More specifically, the study was investigating the number of participants with adverse and serious adverse events in a 14-day timeframe after the last dose, as the primary outcome. The study suspension also caused the candidate’s LoA fall by five points to 6%.

Bayer rise after Phase II AF data

Bayer’s BAY2433334 (asundexian) had its PTSR jump by 10 points to 38% after its Phase II atrial fibrillation trial was announced as completed. Asundexian works by inhibiting coagulation factor XI (FXI). FXI contributes to the development of thrombosis but appears to play a minor role in haemostasis, and so is an attractive anticoagulant target.

The Phase II PACIFIC-AF trial (NCT04218266) update was made public on ClinicalTrials.gov on 13 October, with the PTSR being appraised the next day (14 October). PACIFIC-AF has a primary endpoint investigating asundexian’s ability to positively impact major and clinically relevant non-major bleeding over 12 weeks versus active comparator Bristol Myers Squibb’s Eliquis (apixaban).

Also due to the PACIFIC-AF update, asundexian’s LoA increased by two points to 9%.

Bicycle likely to glide into next stage

Bicycle Therapeutics’ BT-5528 rode ahead with improved chances on its development journey in ovarian and urothelial cancer following a five-point boost in its PTSR. The PTSR reached 36% in both ovarian and urothelial cancers as of 11 October, after the company released interim Phase I results in a 7 October presentation.

The ongoing Phase I/II BT-5528 study (NCT04180371) is recruiting patients with advanced solid tumours positive for EphA2 expression. BT-5528 is an antibody-drug conjugate which binds to EphA2, a member of the Eph subfamily of receptor tyrosine kinases.

As per the interim update, one and two partial responses (PR) were observed among eight and two patients with ovarian and urothelial cancers, respectively. The Phase I data helped establish the recommended Phase II dose range of 6.5–8.5mg/m2 delivered once every two weeks. Neutropenia, anaemia and pneumonitis were the most common adverse events that were Grade 3 or higher. Based on these results, the company is planning expansion cohorts in additional tumour types.

Following the data update, BT-5528’s LoA also rose by one point each in both indications, taking it to 6% in ovarian cancer and 11% in urothelial cancer.

Allogene completes multiple myeloma recruitment

Allogene Therapeutics’ ALLO-605 for relapsed and refractory multiple myeloma (MM) saw its PTSR increase after its Phase I/II trial completed enrolment. The PTSR jumped 20 points to 34% in relapsed MM and 19 points to 35% in refractory MM after ClinicalTrials.gov updated the trial from “recruiting” to “active, not recruiting” on 13 October. The PTSR was updated the next day (14 October).

The 136-patient Phase I/II trial (NCT05000450) is testing ALLO-605 in patients with relapsed or refractory MM following a regimen of fludarabine, cyclophosphamide, and ALLO-647. The Phase I portion’s primary outcomes are evaluating dose-limiting toxicities of ALLO-605 and ALLO-647, while the Phase II portion’s primary endpoint is overall response rate with ALLO-605.

The trial update also resulted in 12-point bump to ALLO-605’s LoA in both relapsed and refractory MM, which sit at 21% and 22%, respectively. ALLO-605, which has FDA Fast Track designation, is an allogenic CAR T therapy targeting B-cell maturation antigen (BCMA) in MM. ALLO-647 is a mAb targeting CD52.

GenSight boosted by new designation

GenSight’s GS-030 for retinitis pigmentosa saw its PTSR jump eight points to 43% after gaining an FDA Fast Track Designation on 12 December. Retinitis pigmentosa is an eye disorder associated with progressive vision loss. GS-030 is a combination of an adeno-associated viruses serotype 2 (AAV2)-based gene therapy and optogenetics designed to treat retinitis pigmentosa.

Paris, France-based GenSight is currently investigating GS-030 in the Phase I/II PIONEER trial (NCT03326336), a 15-patient dose escalation study. The trial, which has a primary endpoint of GS-030 safety and tolerability, has an estimated primary completion date of December 2021. The announcement also bumped GS-030’s LoA up by five points to 24%.

Amphivena completes Phase I AML trial

Amphivena Therapeutics’ bispecific mAb AMV-564 saw its PTSR in refractory acute myeloid leukaemia (AML) jump by 32 points to 39% and 31 points to 37% in relapsed AML following its Phase I trial completion. AMV-564 also saw a 10-point rise in myelodysplastic syndromes (MDS) to 32%; MDS and AML exist along the same disease spectrum.

The completed Phase I study (NCT03144245) had its status changed from “active, not recruiting” as per an 11 October ClinicalTrials.gov update. GlobalData reviewed the asset on 13 October. Phase I sought to evaluate the drug’s safety, tolerability, and preliminary antileukemic activity in 53 subjects diagnosed with AML. AMV-564 works by targeting CD33 and CD3 in a bid for immunostimulatory and antineoplastic effect.

The Phase I update also saw the candidate’s LoA grow across all three indications. The LoA increased by five points to 6% in refractory AML, three points to 4% in relapsed AML, and three points to 9% in MDS. Amphivena is based in San Francisco, California.

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