Who is Daval International?
DAVAL INTERNATIONAL LIMITED is an emerging life sciences company focused on the development and delivery of a novel treatment for serious unmet medical needs through a combination of innovation, dedication, entrepreneurship, skilled science and partnership. From its inception in 2000, the founder and management team of Daval have had a vision of bringing effective treatments that noticeably improve the quality of life of patients suffering from the most serious debilitating neuro-degenerative, inflammatory and autoimmune diseases and to offer a choice over and above some of the disease modifying treatments currently available.
What is AIMSPRO?
AIMSPRO is the trade name of an investigational drug being studied by Daval. It is derived from a manufacturing and product development process that raises hyperimmune caprine serum against an inactivated HIV IIIB viral lysate in goats. The goats are from a special closed herd located in Tasmania, Australia, where the serum is collected. This location has been selected because both Australia and New Zealand are designated as low risk BSE/TSE regions. The collected serum passes to Daval’s production-processor, where the extract is purified in a unique GMP process and then frozen on vialing. The product is then shipped to Daval’s appointed (and MHRA inspected) product holding and handling company - Biotec Distribution (Wales) Limited. Prior to being dispensed to a patient, AIMSPRO is thawed and then administered by subcutaneous injection.
How does AIMSPRO work?
Although the exact mechanism of action of AIMSPRO remains under investigation, initial laboratory studies of the drug observed an anti HLA class II activity. This led to the open label treatment of patients with Primary and Secondary Progressive Multiple Sclerosis and the completion of a pilot study in the latter indication. These studies demonstrated an effect of hyper-acute lowering of sodium channel triggering thresholds in damaged nerve fibres (thus enhancing security of conduction) and led to the expansion of the recipient population to include patients with Charcot-Marie-Tooth disease, Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and a number of Leukodystrophies. The demonstration that an injection with AIMSPRO leads, via a modification of the HPA axis, to a substantial Th-1 to Th-2 cytokine shift (with suppression of TNF-alpha generation) led to AIMSPRO’s use in several rheumatological disorders. Positive “low dose” and “fatal dose” LPS studies in various animal species have underpinned the clinical observations. In addition, studies demonstrating the ability of AIMSPRO to augment the neuroendocrine response and inhibit the mixed lymphocyte response, together with the generation of anti-HLA antibodies, point towards a dampening down of the pro-inflammatory response, which is readily seen as being instrumental in the cause and propagation of pathological processes in many disease states. Because AIMSPRO appears to function through these several mechanisms of action, one of which includes significant anti-inflammatory properties, this is what allows the medication to be considered for use in the treatment of various severe forms of acute and chronic neuro-degenerative, rheumatologic and cutaneous diseases. Daval’s scientists are working to secure further mechanisms of action in the anti-inflammatory and protein kinase regulatory realm.
What is the development status of AIMSPRO?
AIMSPRO has been studied over several years in a number of Daval sponsored and Investigator Initiated clinical trials as well as open label observational studies. These include a long-term six-year study on a patient with Amyotrophic Lateral Sclerosis (ALS - the most common form of Motor Neuron Disease – also known as Lou Gehrig’s Disease), studies in Primary and Secondary Progressive Multiple Sclerosis (including Optic Neuropathy) and established Diffuse Cutaneous Systemic Sclerosis.
Currently, there are two major “proof of concept” clinical studies that have completed enrolment. The first is a Phase II double-blind, placebo controlled human therapeutic clinical study of AIMSPRO in Established Diffuse Cutaneous Systemic Sclerosis, which was conducted at a leading European Scleroderma Unit at the Royal Free NHS Foundation Trust, London, UK. The study has enrolled all the required patients according to strict inclusion/exclusion criteria. Preliminary findings should be available in the summer of 2011, together with secondary and tertiary outcomes (biomarker data) being made available shortly thereafter.
A second randomised, placebo controlled, double blind human Phase II clinical trial focusing on the therapeutic study of bladder instability, a common problem in Secondary Progressive Multiple Sclerosis, has also been completed at the Royal Free Hospital. It was observed in previous open label studies that bladder function in Secondary Progressive Multiple Sclerosis has been improved by treatment with AIMSPRO. The trial design included a double-blind cross-over, so as to increase sensitivity and specificity when determining bladder stability. Enrollment of the subjects in this trial is also complete and preliminary findings are expected to be available in the summer of 2011, with additional secondary and tertiary outcomes being due shortly thereafter.
All these clinical trials undertaken by Daval as sponsor, have been granted local Ethics Committee approvals. Daval were inspected by the MHRA in December 2009 and have demonstrated to the agency’s satisfaction that the company complies with Good Clinical Practice (GCP). In addition, all production and sourcing are fully GMP and GDP compliant.
What is Orphan Drug Designation and how does it help?
AIMSPRO has been granted Orphan Drug designation for the treatment of ALS in the U.S. and Australia. It has also been granted an initial Orphan Drug designation the Therapeutic Goods Administration (TGA) in Canberra, Australia for the treatment of Krabbe disease (also known as globoid cell leukodystrophy) in infants. An orphan disease is one with low prevalence (defined by the FDA as existing in less than one in 200,000 people in the U.S. and by the European Commission as existing in fewer than five of 10,000 people). Orphan designation is granted to programmes demonstrating promise for the diagnosis and/or or treatment of a rare disease. This designation provides regulatory and financial incentives to facilitate the drug development process, but does not allow a drug candidate to bypass the rigorous regulatory pathways required for approval.
Can I participate in clinical trials?
Both of the current Phase II clinical trials for the treatment of Established Diffuse Cutaneous Systemic Sclerosis (Scleroderma) and for Secondary Progressive Multiple Sclerosis (SPMS) are fully enrolled and all the patients have completed their treatment period. The results of both these trials should be available in the summer of 2011. Daval then expects to commence Phase III studies as soon as possible after having had the pivotal trial designs reviewed by the regulatory authorities in the U.S. and Europe. When the next trial is ready to begin enrollment, a full list of participating study sites will be posted at the www.clintrials.gov website, along with contact information for each site. The study summary will also list eligibility criteria for study participants. The selection of patients for these trials will be the responsibility of the Principal Investigator at each participating site in accordance with the clinical trial protocol.
Is AIMSPRO available now through an Early Access/Named Patient/Compassionate Use programme?
AIMSPRO has been granted permission, by the UK’s MHRA, to import AIMSPRO as a “Special”. This allows the drug to be prescribed by UK doctors on a named patient basis to treat patients for “unmet medical needs”. It is also available in Australia under Categories A and B of the TGA’s Special Access Scheme. Daval has recorded that AIMSPRO has been used to treat patients with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Parkinson’s disease, neuropathic pain, Adhesive Arachnoiditis, Myasthenia Gravis, Inflammatory Bowel Disease (Crohn’s Disease and Ulcerative Colitis), Psoriatic Arthritis, Osteoporosis, Ankylosing Spondylitis, Juvenile Arthritis, Dercum’s Disease, chronic venous ulceration, HIV and Hepatitis C. In support of its “named patient programme” Daval has signed a global access pre-approval distribution contract with UK-based Idis Limited, a specialist in named patient programmes. Idis is expert at meeting the import requirements of a vast range of jurisdictions and will manage all non-UK requests for the supply of AIMSPRO to physicians, hospitals and pharmacies until Marketing Authorisation is achieved.
For health care professionals seeking further information about being able to participate in the named patient programme in the UK please contact Daval at: npp@davalinternational.com
For all enquiries about being able to participate in the named patient programme outside of the UK please contact Idis directly via telephone at +44(01)1952 824 100, fax +44 (0)1932 824 300, or via email at customerservices@idispharma.com.
It should be noted that despite the apparent promise of AIMSPRO, it is still under investigation and its long-term safety in a large population of patients has not been fully established and the potential risks of the drug have not yet been totally identified. However, in all the years of continuous administration of AIMSPRO to patients, with well over 500 having received the drug, no medication related serious adverse events have ever been reported and no “Yellow Cards” (the mechanism for enabling the halting of the provision or administration of a drug due to a reported serious adverse event or serious side effect) have ever been recorded by the MHRA.
There has been no event, regulatory intervention or clinical observation which might present an impediment to further commercialisation of AIMSPRO or Ceremben.