Orion's R&D Pipeline

Pipeline presents Orion's key clinical pharmaceutical development projects.

Project Indication Clinical phase / registration      

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.

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.

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.

  More information

 

     

Darolutamide

 Prostate cancer (nmCRPC)

I
II III        

About darolutamide

Darolutamide is a non-steroidal androgen receptor antagonist with a distinct chemical structure that binds to the receptor with high affinity and exhibits strong antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. Darolutamide has shown promising activity in Phase I/II studies in patients with mCRPC.

Orion and Bayer announced on 24 October 2018 that they had completed the phase III clinical trial (ARAMIS) of darolutamide, the novel oral androgen receptor antagonist for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC). The primary endpoint of the trial was met: Darolutamide significantly extended metastasis-free survival compared to placebo. The safety profile and the tolerability of darolutamide observed in the ARAMIS trial were consistent with previously published data on darolutamide.

The more detailed results were presented on 14 February 2019 at American Society of Clinical Oncology Genitourinary Cancers Symposium and simultaneously published in The New England Journal of Medicine. The results show substantial efficacy and a favourable safety profile. Darolutamide plus androgen deprivation therapy (ADT) significantly extends metastasis-free survival with a favorable safety profile compared to placebo plus ADT in non-metastatic castration-resistant prostate cancer.

  • Statistically significant improvement in metastasis-free survival (MFS), with a median MFS of 40.4 months with darolutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT (18.4 months).
  • Positive trend in overall survival with a 29% reduction in risk of death at interim analysis (P=0.045).
  • Incidence of treatment-emergent adverse events was similar for darolutamide plus ADT and placebo plus ADT.
  • Health-related quality of life was maintained.

The rolling submission to FDA for darolutamide in the U.S. has been completed (announced on 27 February 2019) and application for marketing authorisation has also been submitted to the MHLW in Japan (announced on 5 March 2019) and the EMA in Europe (announced on 8 March 2019). Bayer is discussing the data from the ARAMIS trial also with other health authorities regarding the submission for marketing authorization application.  Darolutamide has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment in men with nmCRPC.
 

Commenced in 2014, the ARAMIS trial evaluated the efficacy and safety of darolutamide in patients with non-metastatic castration-resistant prostate cancer who are currently being treated with androgen deprivation therapy (ADT) as standard of care and are at risk of developing metastatic disease. In the double-blind, placebo-controlled trial, more than 1,500 patients were randomized to receive 600 mg of darolutamide or matching placebo twice a day. The primary endpoint was metastasis-free survival, defined as time between randomization and evidence of metastasis or death from any cause.

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.

More information

 

 

ARAMIS study at ClinicalTrials.gov

 

Scientific publications

     

Darolutamide

Prostate cancer (mHSPC)

I II III        

About darolutamide

Orion and Bayer's ongoing Phase III clinical trial (ARASENS)  evaluates the efficacy and safety of darolutamide  in the treatment of patients with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) who are starting hormone therapy. The treatment is darolutamide in combination with hormonal therapy (androgen deprivation therapy) and docetaxel, a chemotherapy drug. The trial, which commenced at the end of 2016, is on track, and patient recruitment was finalized in the review period. The trial is estimated to be completed in 2022.

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.

 

 

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.)

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

More information

Scientific publications

     

ODM-109 (oral levosimendan)

 ALS

I II III        

About ODM-109

In July 2018, Orion recruited the first patients in the Phase III clinical trial (REFALS) in which orally administered levosimendan (ODM-109) is being evaluated for the treatment of symptoms of amyotrophic lateral sclerosis (ALS). The purpose of the trial is to demonstrate that orally administered levosimendan, by enhancing respiratory muscle function, can help maintain breathing capacity and so benefit overall functioning of patients with ALS. Levosimendan does not cure ALS, but it is hoped to maintain the patient’s breathing capacity for longer and thus improve the quality of life by delaying the need for ventilation support. Orion is conducting the trial on its own and investing around EUR 60 million in the study over approximately three years. If the results of the trial are positive, Orion aims is to file for marketing authorisation in the United States and Europe. Orally administered levosimendan has been granted an Orphan Drug Designation both in the United States and in the European Union. Levosimendan is a molecule developed by Orion and launched already in 2000 for the treatment of acute decompensated heart failure.

Orion has on 4 February 2019 announced the intention to start an open label extension study to the ongoing phase 3 trial, REFALS. The extension study, to be known as REFALS-ES, will provide an opportunity for all applicable patients completing the REFALS study to receive oral levosimendan treatment for as long as it is clinically required. The study will provide valuable information on long-term safety and effectiveness of oral levosimendan in patients with ALS.  

About ALS

 
ALS (Amyotrophic lateral sclerosis) is a rare adult-onset neurodegenerative disease of upper and lower motor neurons resulting in progressive weakness, with death occurring from respiratory failure commonly as a result of diaphragmatic weakness typically within three to four years of diagnosis. Poor respiratory function is a major source of disability, fatigue, morbidity and mortality in ALS.

More information


REFALS study at ClinicalTrials.gov

Access Policy for ALS

Scientific publications

     

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.

 

More information


KIDES study at ClinicalTrials.gov

 

Scientific publications

     

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.

 

More information

The study at ClinicalTrials.gov

 

Scientific publications

     

 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.

In the first quarter of 2018, Orion commenced a Phase I clinical trial for the development of a novel selective hormone synthesis inhibitor (CYP11A1 inhibitor) for castration-resistant prostate cancer. In preclinical studies, the molecule (ODM-208) has shown antitumor activity. 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. Orion is the first pharmaceutical company to develop a drug with this mechanism. The trial will investigate the safety and tolerability of the drug candidate in prostate cancer patients, but Orion also plans to study the potential of the molecule for breast cancer treatment.

 

 

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.

More information

The study at ClinicalTrials.gov

Scientific publications

     
 

 

= phase ongoing

     
 

 

= Phase completed

 

 

 

See also:

 Scienfic publications and posters