Darvadstrocel

Last updated

Darvadstrocel
Clinical data
Trade names Alofisel
Other namesCX-601
License data
Routes of
administration
Injection
ATC code
Legal status
Legal status
  • UK: POM (Prescription only) [1]
  • EU:Rx-only [2]
Identifiers
DrugBank
UNII
KEGG

Darvadstrocel, sold under the brand name Alofisel, is a medication used to treat complex perianal fistulas in adults with non-active/mildly active luminal Crohn's disease when fistulas have shown an inadequate response to at least one conventional or biologic therapy. [1] It contains mesenchymal stem cells from fat tissue of adult donors. [2]

Contents

It was approved for use in the European Union in March 2018. [2] The approval was spearheaded by data published in the ADMIRE-CD trial. [2] [3]

It was approved for use in Japan by Japan's Ministry of Health, Labour and Welfare (MHLW) in September 2021. [4]

Medical use

Darvadstrocel has been approved by the European Union for the treatment of adults with complex Crohn's perianal fistulas after conventional or biological medications have not worked. [2]

Mechanism of action

Darvadstrocel works by reducing inflammation and facilitating the growth of tissue in the fistula tract. [2] [3]

History

ADMIRE-CD

The ADMIRE-CD trial was a phase III trial that assessed the safety and efficacy of darvadstrocel vs. placebo in adults with complex perianal fistulas with Crohn's disease. [3] [5] The study randomized a total of 212 patients. [3] 107 patients were given darvadstrocel and 105 patients were given placebo. [3]

After one year, the study found darvadstrocel to be effective in closing external fistula openings, compared to placebo. [3] Patients taking darvadstrocel had a combined remission of 56.3% and clinical remission of 59.2%. [3] The placebo controls had a combined remission of 38.6% and clinical remission of 41.6%. [3]

INSPECT

Published in 2022, the INSPECT study is a retrospective study that evaluated the long-term effectiveness and safety of darvadstrocel in patients with perianal fistulas in Crohn's disease that were treated in the ADMIRE-CD trial. [6] The study data showed that darvadstrocel or the maintenance treatment used can have long term clinical remission in patients. [6]

Related Research Articles

<span class="mw-page-title-main">Ulcerative colitis</span> Inflammatory bowel disease that causes ulcers in the colon

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD). It is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and anemia may also occur. Often, symptoms come on slowly and can range from mild to severe. Symptoms typically occur intermittently with periods of no symptoms between flares. Complications may include abnormal dilation of the colon (megacolon), inflammation of the eye, joints, or liver, and colon cancer.

<span class="mw-page-title-main">Infliximab</span> Biopharmaceutical drug for autommune disorders

Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases. This includes Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, and Behçet's disease. It is given by slow injection into a vein, typically at six- to eight-week intervals.

<span class="mw-page-title-main">Inflammatory bowel disease</span> Medical condition

Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, Crohn's disease and ulcerative colitis (UC) being the principal types. Crohn's disease affects the small intestine and large intestine, as well as the mouth, esophagus, stomach and the anus, whereas ulcerative colitis primarily affects the colon and the rectum.

<span class="mw-page-title-main">Colitis</span> Inflammation of the colon (large intestine)

Colitis is swelling or inflammation of the large intestine (colon). Colitis may be acute and self-limited or long-term. It broadly fits into the category of digestive diseases.

<span class="mw-page-title-main">Natalizumab</span> Medication used to treat multiple sclerosis and Crohns disease

Natalizumab, sold under the brand name Tysabri among others, is a medication used to treat multiple sclerosis and Crohn's disease. It is a humanized monoclonal antibody against the cell adhesion molecule α4-integrin. It is given by intravenous infusion. The drug is believed to work by reducing the ability of inflammatory immune cells to attach to and pass through the cell layers lining the intestines and blood–brain barrier.

<span class="mw-page-title-main">Cladribine</span> Pharmaceutical drug

Cladribine, sold under the brand name Leustatin, among others, is a medication used to treat hairy cell leukemia and B-cell chronic lymphocytic leukemia. Cladribine, sold under the brand name Mavenclad, is used for the treatment of adults with highly active forms of relapsing-remitting multiple sclerosis.

Management of Crohn's disease involves first treating the acute symptoms of the disease, then maintaining remission. Since Crohn's disease is an immune system condition, it cannot be cured by medication or surgery. Treatment initially involves the use of medications to eliminate infections and reduce inflammation. Surgery may be required for complications such as obstructions, fistulae, abscesses, or if the disease does not respond to drugs within a reasonable time. However, surgery cannot cure Crohn's disease. It involves removing the diseased part of the intestine and rejoining the healthy ends, but the disease tends to recur after surgery.

<span class="mw-page-title-main">Certolizumab pegol</span> Pharmaceutical drug

Certolizumab pegol, sold under the brand name Cimzia, is a biopharmaceutical medication for the treatment of Crohn's disease, rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. It is a fragment of a monoclonal antibody specific to tumor necrosis factor alpha (TNF-α) and is manufactured by UCB.

<span class="mw-page-title-main">Biological therapy for inflammatory bowel disease</span>

Biological therapy, the use of medications called biopharmaceuticals or biologics that are tailored to specifically target an immune or genetic mediator of disease, plays a major role in the treatment of inflammatory bowel disease. Even for diseases of unknown cause, molecules that are involved in the disease process have been identified, and can be targeted for biological therapy. Many of these molecules, which are mainly cytokines, are directly involved in the immune system. Biological therapy has found a niche in the management of cancer, autoimmune diseases, and diseases of unknown cause that result in symptoms due to immune related mechanisms.

Ustekinumab, sold under the brand name Stelara, is a monoclonal antibody medication developed by Janssen Pharmaceuticals, for the treatment of Crohn's disease, ulcerative colitis, plaque psoriasis and psoriatic arthritis, targeting both IL-12 and IL-23.

<i>Trichuris suis</i> Species of roundworm

Trichuris suis is a whipworm; the variations in thickness of the anterior and posterior segments give the parasite the characteristic "whip-like" appearance. Adult females measure 6 to 8 cm and adult males 3 to 4 cm. T. suis eggs are oval and yellow-brown with bipolar plugs. T. suis is also used in helminthic therapy studies.

TiGenix is a European cell therapy company with a proprietary validated allogeneic expanded adipose-derived stem cell (eASC) platform technology for the treatment of autoimmune and inflammatory diseases, and a commercialized product. Its corporate headquarters are in Leuven, Belgium, and it has operations in Madrid, Spain. TiGenix was founded in 2000 by Prof. Dr. Frank P. Luyten and Gil Beyen as a spin-off from the Katholieke Universiteit Leuven and the Ghent University.

Vedolizumab, sold under the brand name Entyvio, is a monoclonal antibody medication developed by Millennium Pharmaceuticals, Inc. for the treatment of ulcerative colitis and Crohn's disease. It binds to integrin α4β7, blocking the α4β7 integrin results in gut-selective anti-inflammatory activity.

<span class="mw-page-title-main">Ruxolitinib</span> Medication

Ruxolitinib, sold under the brand name Jakafi among others, is a medication used for the treatment of intermediate or high-risk myelofibrosis, a type of myeloproliferative neoplasm that affects the bone marrow; polycythemia vera, when there has been an inadequate response to or intolerance of hydroxyurea; and steroid-refractory acute graft-versus-host disease. Ruxolitinib is a Janus kinase inhibitor. It was developed and marketed by Incyte Corp in the US under the brand name Jakafi, and by Novartis elsewhere in the world, under the brand name Jakavi.

<span class="mw-page-title-main">Nintedanib</span> Chemical compound

Nintedanib, sold under the brand names Ofev and Vargatef, is an oral medication used for the treatment of idiopathic pulmonary fibrosis and along with other medications for some types of non-small-cell lung cancer.

Teprotumumab, sold under the brand name Tepezza, is a medication used to treat adults with thyroid eye disease, a rare condition where the muscles and fatty tissues behind the eye become inflamed, causing the eyes to bulge outwards.

<span class="mw-page-title-main">Brexpiprazole</span> Atypical antipsychotic

Brexpiprazole, sold under the brand name Rexulti among others, is a medication used for the treatment of major depressive disorder, schizophrenia, and agitation associated with dementia due to Alzheimer's disease. It is an atypical antipsychotic.

<span class="mw-page-title-main">Alicaforsen</span> Chemical compound

Alicaforsen is an antisense oligonucleotide therapeutic that targets the messenger RNA for the production of human ICAM-1 receptor and is being developed for the treatment of acute disease flares in moderate to severe Inflammatory Bowel Disease (IBD).

<span class="mw-page-title-main">Filgotinib</span> Chemical compound

Filgotinib, sold under the brand name Jyseleca, is a medication used for the treatment of rheumatoid arthritis (RA). It was developed by the Belgian-Dutch biotech company Galapagos NV.

<span class="mw-page-title-main">Upadacitinib</span> Chemical compound (medication)

Upadacitinib, sold under the brand name Rinvoq, is a medication used for the treatment of rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, Crohn's disease, ankylosing spondylitis, and axial spondyloarthritis. Upadacitinib is a Janus kinase (JAK) inhibitor that works by blocking the action of enzymes called Janus kinases. These enzymes are involved in setting up processes that lead to inflammation, and blocking their effect brings inflammation in the joints under control.

References

  1. 1 2 "Alofisel 5 million cells/mL suspension for injection - Summary of Product Characteristics (SmPC)". (emc). 12 February 2020. Retrieved 27 February 2020.
  2. 1 2 3 4 5 6 "Alofisel EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 27 February 2020.
  3. 1 2 3 4 5 6 7 8 Panés J, García-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, et al. (April 2018). "Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease". Gastroenterology. 154 (5): 1334–1342.e4. doi: 10.1053/j.gastro.2017.12.020 . PMID   29277560.
  4. NS Healthcare Staff Writer (28 September 2021). "Takeda's Alofisel approved in Japan to treat fistulas in patients with Crohn's disease". NS Healthcare.
  5. "Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn's Disease (ADMIRE-CD)". Clinicaltrials.gov. Archived from the original on 15 June 2012.
  6. 1 2 Panés, Julian; Bouma, Gerd; Ferrante, Marc; Kucharzik, Torsten; Nachury, Maria; de la Portilla de Juan, Fernando; Reinisch, Walter; Selvaggi, Francesco; Tschmelitsch, Jörg; Brett, Neil R.; Ladouceur, Martin (31 January 2022). "INSPECT: A Retrospective Study to Evaluate Long-term Effectiveness and Safety of Darvadstrocel in Patients With Perianal Fistulizing Crohn's Disease Treated in the ADMIRE-CD Trial". Inflammatory Bowel Diseases. 28 (11): 1737–1745. doi:10.1093/ibd/izab361. ISSN   1536-4844. PMC   9629463 . PMID   35099555.

Further reading