25 Nov 5 Companies Developing Innovative Therapeutics for the Treatment of Gout
Gout is a form of inflammatory Arthritis caused by high levels of uric acid in the blood, and is characterised by the formation of needle-like crystals in the joints that cause pain, tenderness and swelling. The disease manifests in four stages namely Asymptomatic hyperuricemia in which crystals are in the formation stage; Acute Gout in which fluctuations in uric acid levels trigger a gout attack and is usually marked by inflammation and pain; Interval Gout is the time period between two subsequent attacks, and finally Chronic Gout, in which uncontrolled uric acid levels lead to damage to joints and loss of mobility.
According to an estimate Gout occurs in 4 percent of Americans Adults and affects over 6 million men and 2 million women in the U.S alone. Blood tests, joint fluid analysis, X-ray, ultrasound, CT or MRI to examine soft tissue and bone are some of the diagnostic methods used to detect the condition. Undetected and untreated Gout can lead to complications such as kidney stones, permanent joint damage or the formation of Tophi under the skin. The severe pain associated with Gout can also have psychological and emotional affects and lead to depression or anxiety.
Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin IB, others) and naproxen sodium (Aleve), are the first recommended course of treatment to help manage the pain and other symptoms associated with the condition. Doctors can also recommend the use of colchicines or Corticosteroids to control the pain and inflammation. However these drugs can cause abdominal pain, bleeding and ulcers nausea, vomiting diarrhea, mood changes, increased blood sugar levels and elevated blood pressure to name a few.
The Global market for Gout Therapeutics will be worth over 9.81 Billion by 2026, growing at a CAGR of 15.2% according to an estimate by Market Study Report. We take a look at some of the emerging treatment paradigms in this area.
Horizon Pharma Public Limited (NASDAQ: HZNP)
Market Cap: $5.91B; Current Share Price: 31.55 USD
Data by YCharts
The Company’s lead candidate for the treatment of adults with chronic gout KRYSTEXXA® (pegloticase injection), is being evaluated in a multicenter, open-label study named PROspective sTudy of pEglotiCase in Transplant patients (PROTECT), in 20 patients with uncontrolled gout who have received a kidney transplant. The study is being conducted at 15 centres across the U.S in collaboration with the American Association of Kidney Patients.
KRYSTEXXA® is a PEGylated uric acid specific enzyme and is used for the treatment of chronic gout in adult patients refractory to conventional therapy. In addition, the Company is also developing HZN-003, a genetically engineered uricase derivative, which is touted to be the next generation gout biologic with optimized uricase and optimized PEGylation technology and HZN-007, an Optimized uricase and PASylation for uncontrolled gout, which is being developed in collaboration with XL-protein GmbH. As per the terms of the agreement the Company will have the right to license the candidates, in case a clinical stage candidate is successfully identified for further development.
Furthermore Horizon has signed a collaboration agreement with HemoShear Therapeutics, LLC for identifying biological targets and treating them using HemoShear’s proprietary REVEAL-Tx™.platform. The Company holds the right to commercialize any successful candidates identified through the collaboration.
The other candidates under development in the Company’s pipeline are Teprotumumab, a fully human monoclonal antibody, insulin-like growth factor-1 receptor (IGF-1R) inhibitor being evaluated for the treatment of active thyroid eye disease (TED) and PROCYSBI Delayed-Release Oral Granules in Packets, for children one year of age and older and adults living with nephropathic cystinosis. The FDA has accepted a New Drug Application for PROCYSBI.
Avion Pharmaceuticals ( Private)
Avion Pharmaceuticals recently entered into a licensing and commercialization agreement with ROMEG Therapeutics, LLC, for exclusive rights to Gloperba, a novel liquid oral dosage form of colchicine indicated for the prophylaxis of gout flares in adults in the U.S market. The drug is helpful in cases where patients may face difficulty in swallowing pills and also enables adjustable dosing, titration and dose reduction options for Gout patients with special needs such as renal or hepatic impairment, resulting in better patient adherence and disease management.
The companies aim to leverage Avion’s expertise in the commercialization process and its extensive sales network along with ROMEG’s aptitude for drug development. The companies plan to extend the partnership to potential joint development of other therapeutics in the future. GLOPERBA® enjoys extensive patent protection covering the formulation, methods of use and administration of ROMEG’s proprietary colchicine oral solution.
Avion is primarily a women and dermatology focused Company, which markets and distributes over six drugs related to prescription prenatal dietary supplements, iron supplements, dermatology and oral contraception in the U.S, such as Chromagen ( multivitamin with iron), FeRiva 21/7, Nicomide ( multivitamin with minerals) and Prenate ( Prenatal multivitamin).
Teijin Limited (OTCPINK: TINLY)
Market Cap: $3.59B; Current Share Price: 19.00 USD
Data by YCharts
Teijin Pharmaceuticals is primarily focusing on bone and joint diseases, respiratory diseases and cardiovascular and metabolic diseases. Febuxostat its lead drug for the treatment of Gout can prevent the formation of excess uric acid in the body as it inhibits the enzyme responsible for the metabolism of uric acid. The drug is now sold in twenty countries including US, Canada, fifteen countries in Europe, Korea, Taiwan and Japan, with plans to expand the sales to over 117 countries in the future.
The Company made a foray into the global home healthcare business with the acquisition of Braden Partners in the US in 2008, besides entering into collaboration with ResMed (NYSE: RMD) of Australia in 2000, for import of Sleep Apnea Syndrome (SAS) ventilator imports. The Company has in-licensed drug candidates from Boehringer Ingelheim, Merck & Co (NYSE: MRK), Takeda GmbH (NYSE: TAK), and Sanofi (NASDAQ: SNY) to name a few. The Company has also out-licensed products such as Tacalcitol to Isdin, Esteve, Merck Sante, Abiogen and Almirall Hermal, its nasal formulation technology to Takeda Pharmaceuticals International, whopping cough vaccine technology to GlaxoSmithKline Biologicals and Sanofi Pasteur.
Rigel Pharmaceuticals (NASDAQ: RIGL)
Market Cap: $385.50M; Current Share Price: 2.30 USD
Data by YCharts
The Company’s lead candidate for the treatment of inflammatory conditions such as psoriasis, rheumatoid arthritis, lupus, multiple sclerosis, inflammatory bowel disease and gout is an investigational drug candidate named R835. The candidate is a potent and selective inhibitor of IRAK1 and IRAK4 that blocks inflammatory cytokine production in response to toll-like receptor (TLR) and the interleukin-1 family receptor (IL-1R) signalling as per a Company statement.
R835 inhibits the production of cytokine in response to TLR and IL-1R activation in vitro and is being tested in a phase 1 clinical study in healthy subjects. The study aims to prove the safety, tolerability and efficacy of R835 in inhibiting both the IRAK1 and IRAK4 signalling pathways, which play a crucial role in inflammation and immune responses to tissue damage.
Rigel also manufactures TAVALISSE®* (fostamatinib disodium hexahydrate) an oral spleen tyrosine kinase (SYK) inhibitor intended for patients with chronic immune thrombocytopenia (ITP) . The Company is expecting a potential EMA approval in ITP in 2019 and is looking at receiving royalties beginning in 2020.
In addition the Company’s pipeline consists clinical candidates being developed in strategic collaborations with BerGenBio (BGBIO.OL) (BGB324 for cancer), Aclaris (NASDAQ: ACRS) ( ATI-501&502 for Dermatology), Daiichi Sankya (DS-3032 for cancer) and AstraZeneca (NYSE: AZN) (AZDO449 for Asthma).
Selecta Biosciences (NASDAQ: SELB)
Market Cap: $66.99M; Current Share Price: 1.39 USD
Data by YCharts
Selecta is leveraging its proprietary immune tolerance platform technology (ImmTOR), to create biologic therapies that can offer novel solutions for diseases, with large unmet medical needs. The Company is targeting rare diseases that have a high immunogenicity, to create a pipeline aimed at therapeutic enzyme and gene therapy product candidates such as chronic refractory gout, for which the Company has developed ImmTOR to be coadministered with its proprietary uricase, pegadricase.
The Company’s proprietary ImmTOR therapy stimulates a selective immune tolerance, by prompting the dendritic cells to create T regulatory cells, which in turn make the immune system more responsive to biologic therapies. This mechanism is extremely important for gene therapies that use the adeno-associated virus (AAV) vectors, as neutralizing antibodies (Nabs) are created in response to AAV vector administration, which makes it impossible to repeat the process in patients who need multiple doses.
This technology is ground-breaking, as it allows for determining an optimal dose for patients who require multiple administrations, and also overcomes the problem of non-replicating AAV vectors, that lose their transgene expression as time passes and pediatric patients grow.
The Company has promising results from its preclinical trials that demonstrate the ability of repeated co-administration of Anc80-Mut, a rationally engineered AAV vector encoding the methylmalonic CoA transgene, and ImmTOR™ was well-tolerated and led to complete inhibition of IgG antibodies as per a Company statement. It also showed a sustained reduction of MMA levels, a higher liver cell DNA copy number and a normalized weight gain in mice models. This offers hope to patients with MMA.
In September 2018, the Company entered collaboration with CureCN, a European consortium to develop an ImmTOR+AAV gene therapy combination product for the treatment of Criggler-Najjar Syndrome. CureCN is likely to carry out the preclinical toxicology studies in the first half of 2019, followed by a combination product candidate that will enter the clinic in the second half of the year.
Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.
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