Clinical trials

Orphazyme is developing arimoclomol in four indications. Orphazyme has reported positive results from a Phase II/III clinical trial in NPC and expects to submit for marketing approval in H1 2020, with potential approval in H2 2020. A Phase II/III trial in sIBM, a Phase III trial in ALS , and a Phase II Proof-of-Concept trial in Gaucher disease are all fully enrolled. Positive Phase II/III trials are intended to form the basis for a single-study filing in each indication.

Arimoclomol Program


Amyotrophic Lateral Sclerosis (ALS)

Orphazyme initiated a Phase III trial in August 2018 to support the application for a marketing authorization in Amyotrophic Lateral Sclerosis (ALS). As previously communicated, the Phase III ALS trial design has been agreed upon with the regulatory authorities: 18-month, placebo-controlled trial including 212 patients. Headline results are expected in H1 2021. The trial design and trial patient baseline characteristics were defined based on systemic analysis of data from the largest publicly available repository of ALS clinical trial data (PROACT) in conjunction with arimoclomol ALS trial data. The primary endpoint is determined as a combined assessment of function and survival.

Sporadic Inclusion Body Myositis (sIBM)

A Phase II/III arimoclomol trial for sporadic Inclusion Body Myositis (sIBM) was initiated in August 2017 in the USA. The trial is intended to support a registration of arimoclomol for the treatment of sIBM. All clinical sites in both the USA and EU are expected to be enrolling patients by Q4 2018. The trial is a 20-month trial with a 12-month interim analysis. Interim results are expected in H1 2020. If positive, the trial may be deemed completed at this point in time for efficacy. In case the trial continues, final study results are expected in H1 2021. The 20-month primary analysis timepoint was made to maximize chances of success, allowing for greater separation between treatment groups at 20 months, while maintaining the possibility to terminate the trial for efficacy after a 12-month interim readout.

Niemann-Pick disease Type C (NPC)

Data from the observational trial, NPC-001, showed a disease progression rate, which confirms the assumptions used to design the Phase II/III trial and candidate biomarkers were analyzed, confirming their potential use as disease biomarkers. Positive full data set announced in Q1 2019. Following EMA and FDA feedback mid-2019, Orphazyme expects to submit for filing in H1 2020, with potential approval in H2 2020.

Gaucher disease

A Phase II clinical trial of arimoclomol for Gaucher disease was initiated in June 2018. The trial takes place at clinical sites in India and will include approximately 40 patients. Patients will be randomized 1:1:1:1 into four treatment arms – active treatment at three different doses and placebo. The patients will receive arimoclomol or placebo-controlled treatment for six months. Following the placebo-controlled period, the placebo group will be re-randomized into one of the three active treatment groups for a six-month extension. Results are expected in H1 2020.

New Molecular Entities

Orphazyme is developing a new series of heat-shock protein (HSP) amplifying drugs based on our expertise and know-how about the convergence of HSPs, protein aggregation, and cellular recycling systems and how these can be targeted for therapeutic benefit. As of the date hereof, Orphazyme has several leads that constitute potentially new intellectual property opportunities.  


About ALS

Amyotrophic Lateral Sclerosis (ALS), also called Lou Gehrig’s disease, is a rapidly progressive and invariably fatal neurological disease. It attacks neurons responsible for controlling voluntary muscles. ALS results in muscle weakness, progressive disability, and eventually death, typically from respiratory failure. Time from onset to mortality is typically short in the range of two to five years. However, ALS is a distinctly heterogeneous disease and the clinical course is variable, with some patients dying within one year from symptom onset and others living for more than a decade.

Muscle weakness results from progressive degeneration of motor neurons in different parts of the central nervous system, where upper and lower neurons selectively die. The cause of damage to the neurons is unknown, but several theories have been proposed, including glutamate toxicity, protein misfolding, and oxidative stress.

Prevalence for ALS
The incidence of ALS is estimated at between 1-3 per 100,000 individuals per year globally. The patient population in the USA and Europe is estimated to be approximately 50,000 patients. In Japan, it is estimated that there are between 8,000-14,000 patients with ALS.



About sIBM

Sporadic Inclusion Body Myositis (sIBM) is an acquired, rare, and slowly progressing muscle disorder which becomes apparent during adulthood. Among individuals older than 50 years it is the most common muscle-wasting disorder. The disease is generally characterized by progressive weakness and degeneration (atrophy) of the muscles, especially those of the arms and legs, particularly in the quadriceps. sIBM typically affects the ability to grab or manipulate objects, causes trouble walking or rising, and can progress to cause severe disability. In addition, difficulty swallowing (dysphagia) due to weakness of throat muscles may occur. sIBM typically presents itself later in life with 87% of patients experiencing onset of symptoms at 50 years of age or more, and earlier symptoms usually only being recognized retrospectively. In most cases, the progression is slow and progresses over the next 10 to 15 years until the affected patient has lost mobility entirely. 

Prevalence for sIBM
The size of the patient population in the USA and Europe is not fully elucidated, but a 2017 publication estimated a patient population of approximately 24.8 and 45.6 per million or at least 30,000 individuals in the USA and the major European countries



About NPC

Niemann-Pick disease Type C (NPC) is a rare, genetic, and progressive disease that impairs the ability of the body to move cholesterol and other fatty substances (lipids) inside the cells. The result is an accumulation of lipids within the body’s tissue, including the brain tissue, causing damage to the affected areas. The symptoms upon onset of NPC vary from fatality during the first months after birth to a progressive disorder not diagnosed until adulthood. The disease affects neurologic and psychiatric functions as well as various internal organs. NPC is usually fatal and the majority of individuals with the disease die before the age of 20. Adults diagnosed with NPC are more likely to present with dementia or psychiatric symptoms. 

Prevalence for NPC
NPC often presents in childhood but can present at any age. The incidence of the disease is estimated to be 1 in 120,000 births and it is estimated that the NPC patient population is between 1,000-2,000 in the USA and Europe.



About Gaucher DISEASE

Gaucher disease is a rare, inherited metabolic disorder causing certain sugar (glucose) containing fat (lipids and especially glycolipids) to abnormally accumulate in the lysosomes of cells, especially within the bone marrow, spleen, and liver, due to the lack of a certain enzyme (glucocerebrosidase). The symptoms vary greatly from patient to patient with some patients having few or no symptoms while others may experience significant complications. The usual symptoms of Gaucher disease include an abnormally enlarged liver and/or spleen (hepatosplenomegaly), low levels of circulating red blood cells (anemia), and blood cells promoting clotting (thrombocytopenia) and skeletal abnormalities. Like NPC, Gaucher disease is an autosomal recessive disorder. 

Prevalence for Gaucher disease
The total number of Gaucher patients in the USA and Europe is conservatively estimated at 10,000-15,000 individuals. Of the total market, Orphazyme focuses on the 10-30% with neuropathic Gaucher disease, where no treatments are available today.


Arimoclomol’s MECHANISM of Action

The production of HSPs is regulated by a transcription factor, heat shock factor 1 (“HSF1”). A transcription factor is a protein that regulates production of other proteins in the cell. In the case of HSF1, the proteins being regulated are HSPs. Activation of HSF1 starts the production of the major stress-inducible HSP70-chaperone along with other HSP-chaperones, which help reshape the cells’ misfolded proteins and take care of the recycling systems. Under normal cellular conditions, HSF1 is inactive. However, the transcription factor can be activated by an initial cellular stress, such as protein misfolding, and becomes fully activated under a sustained stress signal.

Arimoclomol amplifies and prolongs the activated, HSP-producing state of HSF1. This leads to an amplification in the production of cell protective HSPs, but only in physiologically stressed cells. 

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Clinical profile and uses of arimoclomol

The clinical experience with arimoclomol supports its continued development. 


As of the date hereof, no safety risks from taking arimoclomol have been identified in seven Phase I trials and three Phase II trials, and, overall, tolerability of arimoclomol (i.e. the degree to which an overt adverse effect can be tolerated by the subject/patient) was comparable to a placebo. 


Arimoclomol is orally administered and has a bioavailability of 80-90%. High bioavailability reduces the amount of drug administered while achieving the desired pharmacological effect.

In addition, arimoclomol readily crosses the blood-brain barrier. The blood-brain barrier is a selectively permeable membrane which prevents large compounds from entering the cerebrospinal fluid (“CSF”) (liquid surrounding the brain and spinal column). Arimoclomol reaches CSF drug concentrations comparable to the concentration found in circulating blood. Good brain penetrance is key to treatment of many central neurological diseases.


Arimoclomol has achieved a clinical proof-of-concept in treating patients with SOD1 ALS and sIBM. Phase II trials in both indications have shown encouraging and consistent trends of clinically relevant effects in pre-defined analyses that, along with safety data, support moving on to a Phase II/III trial in sIBM patients and a Phase III trial in all patients with ALS both at higher doses.

Early Access Policy

Clinical Trial Access

At Orphazyme, our aim is to positively impact the lives of patients and their families with rare diseases by developing innovative therapies. With our novel treatments in development we strive to help as many patients as possible as fast as possible.  

Obtaining marketing authorization by regulatory authorities like the FDA in the USA and the EMA in the European Union is essential to providing broadest possible access to our treatments. In order to obtain marketing authorization, research in the form of clinical trials is required to evaluate the risks and benefits of the drug in development. Until approved by the national regulatory authorities, the drug remains investigational and is not available to patients. Thus, whenever and wherever possible, we encourage patients to participate in clinical trials.

For those individuals who participate in our clinical trials, we are committed to providing continued access to the investigational drug through the appropriate pathway until safety and efficacy requirements are met and the drug becomes commercially available or reimbursed in their country; or until the program is terminated due unfavorable benefit-risk.

To learn more about available clinical trials please visit:


Early Access

At this time Orphazyme does not have an active Early Access Program in any country, for any of the conditions in which arimoclomol is being developed (i.e. ALS, sIBM, NPC, Gaucher disease).

Orphazyme is currently assessing the possibility of providing access to arimoclomol outside of clinical trials to patients with NPC. We are consulting with regulatory authorities to understand the best way forward towards making arimoclomol available to patients with NPC. Should an Early Access Program for NPC become available, we will work with patient organizations in the country(s) in which the program will open to communicate this information available.

We understand the urgent unmet medical need of patients with rare diseases that we are developing treatments for. Also, we understand that not all patients may be able to participate in clinical trials for various reasons. Depending on the regulations in the country of the patient and based on specific eligibility criteria, Orphazyme will consider providing Early Access to an investigational drug outside of a clinical trial before the product becomes commercially available.

We want to make sure that any access to an investigational drug is provided in an ethical and fair manner while minimizing the risk of harm to the individual patient and avoiding risk to future broader access to the larger patient community in need. Thus, we will take all important aspects of providing Early Access into account in our evaluation, including the patient’s overall situation and the available supporting medical and scientific information.

™Early Access Programs are also called Compassionate Use, Named Patient, Expanded Access and Managed Access Programs. To gain Early Access to an investigational drug, certain criteria need to be met.


Early Access Criteria

Orphazyme will consider granting access to an investigational drug on a case-by-case basis if an Early Access Program is open in the country of residence of the patient and the following criteria are met:


  • The patient has a serious or life-threatening medical condition within the disease area and the patient population that Orphazyme is investigating and planning to pursue approval by the national regulatory authorities.

  • The patient has no access to a suitable approved treatment for the disease condition or no adequate treatments are available.

  • The patient does not qualify to participate in any ongoing or planned clinical trials in a reasonably accessible geographical location.

  • The patient has a disease for which there is sufficient clinical evidence of benefit from the use of the investigational drug, and the benefits likely outweigh the known or anticipated risks.

  • Providing Early Access does not in any way disrupt the clinical development program and/or the regulatory pathway towards marketing authorization leading to broader access.

  • There is an adequate and sustainable supply of the investigational drug, beyond what is required for all ongoing and planned clinical trials.

  • The request for Early Access is received from a licensed physician with expertise in treating the disease and understands the potential risks and benefits of the investigational drug.

  • The requesting physician agrees to comply with Orphazyme’s Early Access Program specifications as well as with the applicable laws and regulations governing the use of the investigational drug.


    Early Access ends once the investigational drug is commercially available or reimbursed in a country. If Orphazyme decides to discontinue clinical development of the investigational drug for a specific disease area, Early Access will be discontinued.


Procedure to Request Early Access

The treating physician who believes that Early Access may be an option for a patient based upon the above criteria, must contact Orphazyme to make a formal request. This will enable the physician to work with Orphazyme to determine the appropriate course of action for the patient.

The request should be submitted here.

Please note that the initial request shall not contain personally identifiable information of the patient (e.g. name, contact details, personal identifications number).

We will acknowledge receipt of such a request within 5 business days. Information on next steps will be provided and a decision on the Early Access will be made as quickly as possible.

The information Orphazyme receives as part of the request will be held under strict confidentiality and managed in accordance with the EU’s General Data Protection Regulations on the protection of natural persons with regard to the processing of personal data and on the movement of such data.

We encourage you to carefully read the Privacy Statement as it contains practical information about the categories of personal data we handle about you, what purpose we may use and process such data with and how you exercise your legal rights you have in this respect.