Data From RNAi In Hep B And A Novel Dermatitis Antibody

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Includes: ABUS, AMGN, AZN, REGN
by: EP Vantage

Welcome to your weekly digest of approaching regulatory and clinical readouts. Phase II data from Arbutus Biopharma’s (NASDAQ:ABUS) hepatitis B treatment ARB-1467 are expected in the second half. It is an RNAi therapeutic geared towards curing the disease, so impressive data could see partners emerge.

Also Amgen’s (NASDAQ:AMGN) phase II study of tezepelumab in atopic dermatitis is expected to complete next month. The product is also being studied in asthma. Both therapy areas are crowded with interleukin-targeting antibodies so tezepelumab will need to differentiate itself.

RNAi approach

Data from Arbutus’ phase II multi-dosing trial is expected to report in the third or fourth quarter. ARB-1467 is an RNAi therapeutic that targets hepatitis B surface antigen (HBsAg) expression. Single dose HBsAg reduction data will be reported first, with multi-dose data following.

Chronic hepatitis B infected patients who were on a stable nucleoside or nucleotide analogue therapy were given three monthly doses of ARB-1467 at 0.2 or 0.4mg/kg, or placebo. The trial recruited 24 patients across three cohorts depending on the expression of a particular antigen, with two patients receiving placebo in each cohort.

According to consensus from EvaluatePharma, ARB-1467 sales are expected to reach $155m by 2022, which would make it the fifth biggest hep B drug that year (see table). Arrowhead’s ARC-520, another RNAi therapeutic, takes the third spot. ARC-520 is intended to disrupt production of hep B proteins necessary for the virus to replicate and is in a number of phase II trials.

Arrowhead’s candidate is also unpartnered, and an impressive readout could attract a collaborator. As Arbutus’s main growth driver for the foreseeable future, investors in the company, which was previously known as Tekmira Pharmaceuticals, will be watching with interest.

Top 5 Hep B products in 2022

Annual WW Sales (Indication) $m

Product

Company

Pharma class

2016

2018

2020

2022

WW indication status

Tianqingganmei

Sino Biopharmaceutical (OTCPK:SBMFF)

Hep B agent

354

477

628

811

Marketed

Runzhong

Sino Biopharmaceutical

Nucleoside analogue

489

611

706

801

Marketed

ARC-520

Arrowhead Pharmaceuticals (NASDAQ:ARWR)

RNAi therapeutic

-

13

238

463

Phase II

Baraclude

Bristol-Myers Squibb (NYSE:BMY)

Nucleoside analogue

1,117

648

433

330

Marketed

ARB-1467

Arbutus Biopharma

RNAi therapeutic

-

-

29

155

Phase II

Other

1,329

854

594

542

Total

3,288

2,603

2,628

3,102

Crowded antibody market

Tezepelumab is an anti-thymic stromal lymphopoietin (TSLP) monoclonal antibody. TSLP is an IL-7-like cytokine expressed by skin keratinocytes and airway epithelial cells in response to irritating stimuli, which initiates signalling pathways leading to inflammation driven by type 2 helper T cells.

The phase II trial, called Alleviad, tests tezepelumab in adult patients with moderate to severe atopic dermatitis. The primary endpoint is 50% reduction from baseline in the Eczema Area and Severity Index (EASI 50) measured at week 12 compared with placebo. The monoclonal antibody, also known as AMG 147/MEDI9929, is administered by subcutaneous injection.

The MAb, for which Amgen has a profit share with AstraZeneca (NYSE:AZN), is also in a large trial in adults with inadequately controlled, severe asthma. The 552-patient trial is testing three doses of tezepelumab against placebo. The primary endpoint is the rate of asthma exacerbations and the trial has a primary completion date of December this year.

The results of a 32-patient phase I trial were reported back in 2014. Treatment with tezepelumab resulted in statistically significant reductions in early and late asthmatic response in the airways following allergen challenges in patients with allergic atopic asthma. Adverse events were similar across treatment and placebo groups.

Both dermatitis and asthma pipelines are crowded with monoclonal antibodies mostly targeting specific interleukins. Sanofi (NYSE:SNY) and Regeneron's (NASDAQ:REGN) dupilumab could be the first systemic drug to treat atopic dermatitis. A rolling submission will likely be completed by the end of the year and it is also being tested in asthma (Dupilumab grabs atopic dermatitis head start, April 1, 2016).

While competition is high, the only other anti-TSLP MAbs in development are Glaxo’s GSK3191812, which is yet to enter the clinic, and a research project from South Korean group BIO-FD&C, according to EvaluatePharma data. As the most advanced in its class tezepelumab will be hoping to find its niche.

Product

Trial name

Trial ID

ARB-1467

-

NCT02631096

Tezepelumab

Alleviad

NCT02525094

Tezepelumab

(Phase I asthma trial)

NCT01405963

Tezepelumab

(Phase II asthma trial)

NCT02054130