Orion's R&D Pipeline

Pipeline presents Orion's key clinical pharmaceutical development projects.

Project Indication Clinical phase / registration

Easyhaler® salmeterol-fluticasone

Asthma, COPD

I
II III  R

About Easyhaler salmeterol-fluticasone

An inhaled Easyhaler® salmeterol-fluticasone combination product is indicated for asthma and chronic obstructive pulmonary disease (COPD). In this formulation, fluticasone acts as an anti-inflammatory agent and salmeterol acts as a long-acting bronchodilator.

Orion's Easyhaler® is an in-house developed dry-powder inhaler. Orion has developed Easyhaler-adapted dry powder formulations of several well-known generic active substances (salbutamol, beclometasone, budesonide, formoterol and budesonide-formoterol combination) used in the treatment of asthma and COPD. At the moment under development is new combined formulation of fluticasone-salmeterol for the treatment of asthma and COPD.

About Asthma and COPD

Asthma is a common airway disease characterized with airway inflammation and variable airway obstruction. Typical sypmtoms included chronic cough, wheezing and dyspnea. Chronic Obstructive Pulmonary Disease is most often related to smoking that causes airway inflammation and airway obstruction that is mostly not reversible. Symptoms include cough, mucus production and breathlessness. Frequent exacerbations during respiratory infections are also common. Asthma and COPD are mostly treated with inhaled medication.

Related releases and publications

Orion Corporation has in March 2018 received positive conclusions for the salmeterol-fluticasone Easyhaler® combination under the EU's decentralized procedures (DCP). The decentralized procedures concern 22 countries, with Sweden acting as the reference member state. National approval procedures of the marketing authorisation applications will start in the following EU Member States: Belgium, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Hungary, Iceland, Italy, Latvia, Lithuania, Luxemburg, the Netherlands, Norway, Poland, Portugal, Slovakia, Slovenia, Spain, Sweden and United Kingdom.

Study at ClinicalTrials.gov

Easyhaler® tiotropium

COPD

Bioequivalence study ongoing

About Easyhaler tiotropium

An inhaled Easyhaler® tiotropium product is indicated for chronic obstructive pulmonary disease (COPD) . Tiotropium is a long-acting anticholinergic bronchodilator used in the management of chronic obstructive pulmonary disease (COPD). Orion's Easyhaler® is an in-house developed dry-powder inhaler.

Orion has developed Easyhaler-adapted dry powder formulations of several well-known generic active substances (salbutamol, beclometasone, budesonide, formoterol and budesonide-formoterol combination) used in the treatment of asthma and COPD. At the moment under registration is new combined formulation of fluticasone-salmeterol for the treatment of asthma and COPD.

About COPD

Chronic Obstructive Pulmonary Disease is most often related to smoking that causes airway inflammation and airway obstruction that is mostly not reversible. Symptoms include cough, mucus production and breathlessness. Frequent exacerbations during respiratory infections are also common. Asthma and COPD are mostly treated with inhaled medication.

    Related releases and publications

Orion announced in its Financial Statement Release 2017 on 7 February 2018 that it is developing a tiotropium formulation for European markets, and a bioequivalence study with the formulation is ongoing.

Darolutamide (ODM-201)

 Prostate cancer (nmCRPC)

I
II III  

About darolutamide

Darolutamide is an investigational oral androgen receptor (AR) antagonist that has a unique chemical structure designed to block the growth of cancer cells through binding to the AR with high affinity and inhibiting the receptor function. In preclinical studies, darolutamide and its main circulating metabolite are active also in known AR mutants (ex W742L, F877L), and have been found to have negligible blood-brain barrier penetration. 

 

Darolutamide is developed in collaboration with Bayer

About prostate cancer

Prostate cancer is the second most commonly diagnosed malignancy in men worldwide. Hormonal deprivation therapy allows long-lasting and effective control of cancer-related symptoms in advanced stages. Despite effective treatment strategies, in some patients with prostate cancer the disease will progress and become castration-resistant. CRPC is characterized by persistent, high level AR function and resistance to conventional anti-androgens such as bicalutamide. Effective treatment options for castrate-resistant patients are still limited, with the field evolving rapidly.

Related releases and publications

 

Orion announced on 3 April 2018 that the estimated primary completion date for the joint Phase III clinical trial ARAMIS with darolutamide (NCTNCT02200614)  by Orion and Bayer has been updated in the https://clinicaltrials.gov/ -online service. The estimated primary completion date is now updated to September 2018.

ARAMIS study at ClinicalTrials.gov

Research posters & articles

EAU 2016: Updated long term efficacy and safety of androgen receptor inhibitor ODM-201 in phase I/II trial


ODM-201: a new-generation androgen receptor inhibitor in castration-resistant prostate cancer

Bone Scan Index and progression-free survival data for progressive metastatic castration-resistant prostate cancer patients who received ODM-201 in the ARADES multicentre study

Pharmacokinetics, Antitumor Activity, and Safety of ODM-201 in Patients with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer: An Open-label Phase 1 Study

Discovery of ODM-201, a new generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies

EAU 2015 Massard et al.

ASCO 2014  Massard et al.

EAU 2014

AACR 2014 ODM-201 AR mutation data

ASCO GU 2014 Garcia et al.

ASCO GU 2014 Massard et al.

ASCO GU 2014 Shore et al.

ESMO 2013 nonclinical poster

ASCO GU 2013

ESMO 2012: ARADES poster 

Darolutamide (ODM-201)

Prostate cancer (mHSPC)

I II III  

About darolutamide

Darolutamide is an investigational oral androgen receptor (AR) antagonist that has a unique chemical structure designed to block the growth of cancer cells through binding to the AR with high affinity and inhibiting the receptor function. In preclinical studies, darolutamide and its main circulating metabolite are active also in known AR mutants (ex W742L, F877L), and have been found to have negligible blood-brain barrier penetration.

 

Darolutamide is developed in collaboration with Bayer

About prostate cancer

Prostate cancer is the second most commonly diagnosed malignancy in men worldwide.

At the time of diagnosis, most men have localized prostate cancer, meaning their cancer is confined to the prostate gland and can be treated with curative surgery or radiotherapy. Upon relapse when the disease will metastasize or spread, androgen deprivation therapy (ADT) is the cornerstone of treatment for this hormone-sensitive disease. Approximately five percent of men will already suffer from prostate cancer with distant metastases when first diagnosed. (Source: University of Maryland Medical Center. Prostate Cancer. Available at: http://umm.edu/health/medical/reports/articles/prostate-cancer.)

Men with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) will start their treatment with hormone therapy, such as ADT or a combination of the chemotherapy docetaxel and ADT. Despite this first line treatment, most men with metastatic HSPC will eventually progress to castration-resistant prostate cancer (CRPC), which can impact survival and quality of life. (Source: National Cancer Institute. Hormone Therapy for Prostate Cancer. Available at: http://www.cancer.gov/types/prostate/prostate-hormone-therapy-fact-sheet.)

 Related releases and publications

ODM-109 (oral levosimendan)

 ALS

I II III  

About ODM-109

In 2016, Orion completed the Phase II clinical trial with orally administered levosimendan (ODM-109) for treatment of patients with amyotrophic lateral sclerosis (ALS). Although the trial did not achieve its primary objective, the findings were, however, promising. Based on the findings, Orion decided in the first quarter of 2018 to commence a Phase III clinical trial. The costs of the trial are estimated at approximately EUR 60 million over approximately three years. The objective of the trial is to develop oral levosimendan for symptomatic treatment for the primary symptom of ALS, muscle weakness. In previous studies, levosimendan has shown positive effect on diaphgram muscle function. Levosimendan has already been studied as a treatment for heart failure among other things, which will speed up the commencement of the programme. Simdax® (levosimendan) is Orion's proprietary drug for the intravenous treatment of acutely decompensated heart failure sold in more than 50 countries through Orion Corporation or its partners. So far, oral levosimendan does not have marketing authorization in any indicationThe US Food and Drug Administration (FDA) has granted ODM-109 an Orphan Drug Designation.

About ALS

 
ALS (Amyotrophic lateral sclerosis) is a rare, rapidly progressive neurological disease characterised by degeneration of upper and lower motor neurons with subsequent muscle atrophy, weakness and loss of voluntary movements and respiratory function. The latter is due to the weakness and loss of the diaphragm muscle function. Respiratory failure is the most common cause of death in ALS.

Research posters

MND Congress, Dec 2017: Poster 1
MND Congress, Dec 2017: Poster 2

Press release on 6 July 2018


REFALS study at ClinicalTrials.gov

Access Policy for ALS

ODM-104

(more effective COMT inhibitor)

 Parkinson's disease

I
II    

About ODM-104

ODM-104 is a new molecule that enhance the therapeutic effects of levodopa used to treat Parkinson’s disease by blocking the COMT enzyme. The pre-clinical study results indicated that ODM-104 is more effective than the COMT inhibitor entacapone, which is already in the markets.

 

Orion announced in its Half-Year Financial Report on 18 July 2018 that it has completed the Phase II trial. The primary endpoint was reached. The results are being analysed, and Orion is evaluating moving on to Phase III.  Orion is looking for a possible partner for the trial.

About Parkinson's disease

Parkinson’s disease is a progressive neurological disorder. Symptoms typical of Parkinson's disease, such as slowness of movements, stiffness and tremor, are caused by the brain's inability to produce enough dopamine, a neurotransmitter important for the body's motor functions. Levodopa is the natural precursor of dopamine and thus the standard drug used in the treatment of Parkinson's symptoms. When used alone, most of levodopa is metabolised in the body before it reaches the brain. Enzyme inhibitors such as entacapone have thus been developed to enhance the effect of levodopa. An unmet medical need has however been identified for novel and even more effective levodopa treatments.

 

 Related releases and publications

NOCIFIM study at ClinicalTrials.gov

ODM-203

(targeted FGFR+VEGFR inhibitor)

 Solid tumours

I II    

About ODM-203

ODM-203 is an investigational targeted Fibroblast Growth Factor Receptor (FGFR) + Vascular Endothelial Growth Factor Receptor (VEGFR) inhibitor that is designed to block growth of FGFR signaling dependent tumours. ODM-203 is unique as it is a selective and equally potent inhibitor against both the FGFR and VEGFR family kinases. In accordance ODM-203 shows strong antitumour activity in both FGFR and VEGFR dependent nonclinical tumour models.

About solid tumors with genomic alterations in FGFR

Dysregulation of the FGFR signaling pathway has been associated with several types of solid tumors. Furthermore, both FGFRs and VEGFR signaling are known drivers of angiogenesis in solid tumors. Such tumors are for example bladder cancer, breast cancer and lung cancer. Many different molecules targeting FGFR are currently in preclinical and clinical development by various pharmaceutical companies.

 

 Related releases and publications

Cholangiocarcinoma Foundation Annual Conference, Feb 2017: Phase 1 study of ODM-203, a selective dual FGFR/VEGFR inhibitor, in patients with advanced solid tumours.

ESMO 2016: ODM-203 Phase I study poster Rodon et al 2016

ASCO 2016: Dose escalation study of ODM-203. Rodon et at 2016

TAT 2016: ODM-203 dose escalation study poster

AACR 2015: ODM-203 nonclinical poster Holmström et al 2015


KIDES study at ClinicalTrials.gov

ODM-207 (BET protein inhibitor)

 Cancer

  I
     
 

About ODM-207

ODM-207 is an investigational small molecule that has a unique chemical structure designed to block the growth of cancer cells through potent and selective inhibition of BET family proteins. In preclinical studies, ODM-207 has shown antiproliferative effects in several haematological and solid tumour cell lines.

  Related releases and publications

 2nd European Cancer Epigenetics Conference, May 2017: Targeting cancer with a novel BET bromodomain inhibitor

AACR, April 2017: Targeting cancer with a novel BET bromodomain inhibitor

AACR, April 2017: Immune-mediated anti-tumor activity with a clinical stage BET bromodmain inhibitor ODM-207 in pre-clinical models

 

AACR 2016: ODM-207 nonclinical poster 2016 Björkman et al

 

 ODM-208 (CYP11A1 inhibitor)

 Prostate cancer (CRPC)

 I       

About ODM-208

Steroid hormones stimulate the growth of hormonally regulated cancers, such as most prostate and breast cancers. Hormonal treatments are highly effective, but drug resistance will often eventually emerge and cancer will start growing again.

Orion has in Q1/2018 commenced a Phase I clinical trial for development of  a novel selective hormone synthesis inhibitor (CYP11A1 inhibitor) for castration-resistant prostate cancer. The trial will investigate the safety and tolerability of the drug candidate in prostate cancer patients.

In preclinical studies, the molecule (ODM-208) has shown antitumor activity. ODM-208 inhibits the synthesis of steroids hormones. It has potential efficacy also for those cancers that have become resistant to the standard hormonal treatments.

The steroid hormones that are needed and do not promote cancer growth are replaced with additional medication.

 

 

About prostate cancer

Prostate cancer is the second most commonly diagnosed malignancy in men worldwide.Hormonal deprivation therapy allows long-lasting and effective control of cancer-related symptoms in advanced stages. Despite effective treatment strategies, in some patients with prostate cancer the disease will progress and become castration-resistant. CRPC is characterized by persistent, high level AR function and resistance to conventional anti-androgens such as bicalutamide. Effective treatment options for castrate-resistant patients are still limited, with the field evolving rapidly.

 Related releases and publications


ASCO 2018: CYP11A1 inhibition as a therapeutic  approach fot the treatment of castration resistant prostate cancer

ESMO 2017: ODM-208, a novel CYP11A1-inhibitor as a therapeutic approach for the treatment of castration-resistant prostate cancer

 

 

= phase ongoing

 

 

= Phase completed