Dendreon

Last updated
Dendreon
Type Private
Industry Biomedicine
Founder William A. Haseltine
Edgar Engleman
Samuel Strober
Headquarters
Seal Beach, California
,
US
ProductsProvenge
ServicesProvenge
Number of employees
650
Parent Sanpower Group, Nanjing, CN
Website dendreon.com

Dendreon is a biotechnology company. Its lead product, Provenge (known generically as sipuleucel-T), is an immunotherapy for prostate cancer. It consists of a mixture of the patient's own blood cells (autologous, with dendritic cells thought to be the most important) that have been incubated with the Dendreon PAP-GM-CSF fusion protein. Phase III clinical trial results demonstrating a survival benefit for prostate cancer patients receiving the drug were presented at the AUA meeting on April 28, 2009. [1] After going through the approval process, Provenge was given full approval by the FDA on April 29, 2010. [2] Dendreon's stock value fell 66% on August 4, 2011, after abandoning its forecast for its debut drug Provenge. [3]

Contents

In November 2014, Dendreon filed for Chapter 11 bankruptcy protection and shortly afterwards announced that it had reached agreements on the terms of a financial restructuring with certain bond holders. [4]

On February 20, 2015, Valeant Pharmaceuticals received approval to purchase all Dendreon assets. On January 9, 2017 Sanpower Group agrees to acquire Dendreon from Valeant for $819.9 million [5] In June 2017, Sanpower Group, a Chinese conglomerate, purchased Dendreon from Valeant for $820 million. [6]

Technology overview and pipeline

Antigen delivery cassette and antigen presenting cells

Dendreon's name derives from the "Dendritic Cell" which forms a major component of the company's product candidates that use the "Dendreon Cassette Technology" to insert a disease-specific target protein into a general platform. Their lead product, Provenge, is an example of their "rationally designed therapeutic process" intended to break immune tolerance to certain disease specific proteins. It is hypothesized that receptor mediated uptake of antigen by dendritic cells occurs when they are exposed to the Dendreon fusion protein which links the disease specific protein to a recognition protein. This approach is in contrast to other dendritic cell vaccines that use methods such as electroporation to get the DC's to present antigen related epitopes. In the case of Provenge, this disease related protein is prostatic acid phosphatase and the signalling component is GM-CSF.

Antigen selection

Dendreon believes its process can be optimized and generalized to other diseases by exchanging the PAP component of Provenge with better targets specific to different diseased cells. [7] Antigen selection is a significant issue with cancer vaccines in general. Presumably, therapeutic effect can be obtained by provoking a selective response against the diseased cells only. Dendreon has explored approaches to obtaining tumour-specific antigen targets under the theory that the immune system may be able to mount a more effective response than is otherwise possible against tumor associated antigens. Unaltered human PAP is expressed by normal prostate cells but recent discoveries suggest that cancer cells produce many more unique targets as well as proteins that are more highly expressed than in normal tissue. [8] It has also been recently discovered that other enzymes expressed in nerves are identical to PAP [9] [10] and there is ongoing work to examine post-translational modifications to PAP and its correlation to disease state by Dendreon collaborators. [11] PAP also appears to be expressed in breast cysts. [12]

Prior work in this area has also included that of A. Sette at Epimmune and the Altered Peptide Ligand approach typified by Neurocrine Biotech's failed MS drug.

Nuvelo and patents acquired from Corvas

Dendreon acquired the nematode anticoagulant Nuvelo. [13] Selected Corvas patents include technologies for peptide analog synthesis and drugs that target coagulation and immune processes.

Early history

Drs. Haseltine, Engleman, and Strober established the company, initially named Activated Cell Therapy, in Mountain View, California, after securing funding from Health Care Ventures in Edison, New Jersey. The company successfully brought to market the first approved cell-based immune therapy, Provenge, for the treatment of metastatic prostate cancer [14] After several years the company changed its name to Dendreon and moved to Seattle, Washington, under Christopher Henney.

Provenge

Initial clinical results for Provenge in 2000 showed immune responses supporting the expected mode-of-action, as well as a PSA reduction which was thought to relate to clinical improvement. [15] In 2006, Dendreon built a manufacturing facility in Morris Plains, New Jersey to accommodate production for a Phase III trial and possible 2007 drug approval by the U.S. Food and Drug Administration (FDA). [16] In January 2007, the FDA accepted Dendreon's Biologic License Application (BLA) filing for Provenge. [17]

On March 29, 2007, the FDA Office of Cellular, Tissue and Gene Therapies Advisory Committee voted 17-0 that Provenge is reasonably safe and 13-4 that the trial data showed substantial evidence that it is effective. [18] However, on May 9, 2007, Dendreon received a letter from the FDA demanding more results and information before approval. [19]

On April 14, 2009, Dendreon announced that the results for the Phase III trial of Provenge were positive, saying there had been a reduction in the odds of death compared to the use of a placebo. [20] On April 28, 2009, the full details of the study were released. The trial found that patients treated with Provenge lived an average of 4.1 months longer than patients treated with the control (autologous cells without the GM-CSF / PAP fusion protein). [21]

On April 29, 2010, the FDA approved Provenge for use in the treatment of advanced prostate cancer.

On June 7, 2010, the head of Medicare's Coverage and Analysis Group, Dr. Louis Jacques, sent three colleagues an email telling them that they should be sure not to leak the fact that his Group was considering a cap on Medicare coverage of this treatment. News of that caution itself did inevitably leak, and the price of Dendreon's stock fell 10% later that day.

Dendreonites

Some journalists have referred to Provenge supporters as "Dendreonites" and the name is in routine usage in colloquial forums. [22] Concerns for personal safety were raised among some doctors who were thought responsible for the delay of Provenge approval. [23] Dendreonites have questioned these doctors' objectivity; one of them, Dr. Howard Scher, was the lead clinical trial investigator for a rival prostate cancer drug from the biotech company Novacea. [22] Their concerns motivated organized protests at the FDA and American Society of Clinical Oncology (ASCO) meeting by various patient and investor advocacy groups which also filed a lawsuit alleging that the FDA's decision was influenced by conflicts of interest. [24]

Related Research Articles

Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies. Immunotherapy is under preliminary research for its potential to treat various forms of cancer.

A cancer vaccine is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as therapeutic cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", being prepared from samples taken from the patient, and are specific to that patient.

<span class="mw-page-title-main">Cancer immunotherapy</span> Artificial stimulation of the immune system to treat cancer

Cancer immunotherapy is the stimulation of the immune system to treat cancer, improving on the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology and a growing subspecialty of oncology.

Virotherapy is a treatment using biotechnology to convert viruses into therapeutic agents by reprogramming viruses to treat diseases. There are three main branches of virotherapy: anti-cancer oncolytic viruses, viral vectors for gene therapy and viral immunotherapy. These branches use three different types of treatment methods: gene overexpression, gene knockout, and suicide gene delivery. Gene overexpression adds genetic sequences that compensate for low to zero levels of needed gene expression. Gene knockout uses RNA methods to silence or reduce expression of disease-causing genes. Suicide gene delivery introduces genetic sequences that induce an apoptotic response in cells, usually to kill cancerous growths. In a slightly different context, virotherapy can also refer more broadly to the use of viruses to treat certain medical conditions by killing pathogens.

<span class="mw-page-title-main">Prostatic acid phosphatase</span> Human protein

Prostatic acid phosphatase (PAP), also prostatic specific acid phosphatase (PSAP), is an enzyme produced by the prostate. It may be found in increased amounts in men who have prostate cancer or other diseases.

<span class="mw-page-title-main">RANKL</span> Mammalian protein found in Homo sapiens

Receptor activator of nuclear factor kappa-Β ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiation factor (ODF), is a protein that in humans is encoded by the TNFSF11 gene.

<span class="mw-page-title-main">Monoclonal antibody therapy</span> Form of immunotherapy

Monoclonal antibody therapy is a form of immunotherapy that uses monoclonal antibodies (mAbs) to bind monospecifically to certain cells or proteins. The objective is that this treatment will stimulate the patient's immune system to attack those cells. Alternatively, in radioimmunotherapy a radioactive dose localizes a target cell line, delivering lethal chemical doses. Antibodies have been used to bind to molecules involved in T-cell regulation to remove inhibitory pathways that block T-cell responses. This is known as immune checkpoint therapy.

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

Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.

<span class="mw-page-title-main">CD33</span> Mammalian protein found in Homo sapiens

CD33 or Siglec-3 is a transmembrane receptor expressed on cells of myeloid lineage. It is usually considered myeloid-specific, but it can also be found on some lymphoid cells.

Northwest Biotherapeutics is a development-stage American pharmaceutical company headquartered in Maryland that focuses on developing immunotherapies against different types of cancer. It was founded in 1996 by Alton L. Boynton.

Simon J. Hall, M.D., is the Associate Professor and Kyung Hyun Kim, M.D. Chair of Urology and Assistant Professor, Department of Gene and Cell Medicine at The Mount Sinai School of Medicine, as well as the Director of the Barbara and Maurice Deane Prostate Health and Research Center at The Mount Sinai Medical Center, both in New York City.

Biovest International, Inc was a Minneapolis-based biotechnology company. Their active immunotherapy, BiovaxID, is a cancer vaccine whose first indication was intended to be consolidation/adjuvant therapy of follicular Non-Hodgkin's Lymphoma. Biovest filed to reorganize under chapter 11 bankruptcy in 2014, BiovaxID was refused European marketing authorization in 2015, and Biovest's stock listing was revoked in 2017.

Sipuleucel-T, sold under the brand name Provenge, developed by Dendreon Pharmaceuticals, LLC, is a cell-based cancer immunotherapy for prostate cancer (CaP). It is an autologous cellular immunotherapy.

Neuvenge, Lapuleucel-T, is a therapeutic cancer vaccine (TCV) in development by Dendreon (DNDN). It uses the "immunotherapy platform approach" first successfully demonstrated on the U.S. Food and Drug Administration (FDA)-approved TCV Provenge. It was first tested on breast cancer patients with tumors expressing HER2/neu, and is now scheduled to be tested on bladder cancer patients.

<span class="mw-page-title-main">Talimogene laherparepvec</span>

Talimogene laherparepvec, sold under the brand name Imlygic, is a biopharmaceutical medication used to treat melanoma that cannot be operated on; it is injected directly into a subset of lesions which generates a systemic immune response against the recipient's cancer. The final four year analysis from the pivotal phase 3 study upon which TVEC was approved by the FDA showed a 31.5% response rate with a 16.9% complete response (CR) rate. There was also a substantial and statistically significant survival benefit in patients with earlier metastatic disease and in patients who hadn't received prior systemic treatment for melanoma. The earlier stage group had a reduction in the risk of death of approximately 50% with one in four patients appearing to have met, or be close to be reaching, the medical definition of cure. Real world use of talimogene laherparepvec have shown response rates of up to 88.5% with CR rates of up to 61.5%.

Tolerogenic therapy aims to induce immune tolerance where there is pathological or undesirable activation of the normal immune response. This can occur, for example, when an allogeneic transplantation patient develops an immune reaction to donor antigens, or when the body responds inappropriately to self antigens implicated in autoimmune diseases. It must provide absence of specific antibodies for exactly that antigenes.

The dendritic cell-based cancer vaccine is an innovation in therapeutic strategy for cancer patients.

The Immune Response Corporation (IRC) pioneered immunotherapeutic products. The firm was founded by Jonas Salk and Kevin Kimberlin when Kimberlin, "asked Salk to become lead scientific advisor for a new biotech company specializing in 'anti-idiotypes,' a novel vaccine technology," Salk called the proposal "liberating."

A therapeutic vaccine is a vaccine which is administered after a disease or infection has already occurred. A therapeutic vaccine works by activating the immune system of a patient to fight an infection. A therapeutic vaccine differs from a prophylactic vaccine in that prophylactic vaccines are administered to individuals as a precautionary measure to avoid the infection or disease while therapeutic vaccines are administered after the individual is already affected by the disease or infection. A therapeutic vaccine fights an existing infection in the body rather than immunizing the body for protection against future diseases and infections. Therapeutic vaccines are mostly used against viral infections. Patients affected with chronic viral infections are administered with therapeutic vaccines, as their immune system is not able to produce enough efficient antibodies.

mRNA vaccine Type of vaccine

An mRNAvaccine is a type of vaccine that uses a copy of a molecule called messenger RNA (mRNA) to produce an immune response. The vaccine delivers molecules of antigen-encoding mRNA into immune cells, which use the designed mRNA as a blueprint to build foreign protein that would normally be produced by a pathogen or by a cancer cell. These protein molecules stimulate an adaptive immune response that teaches the body to identify and destroy the corresponding pathogen or cancer cells. The mRNA is delivered by a co-formulation of the RNA encapsulated in lipid nanoparticles that protect the RNA strands and help their absorption into the cells.

References

  1. ↑ "AUA IMPACT Trial Presentation Summary" (PDF).
  2. ↑ "UPDATE 3-U.S. FDA OKs Dendreon's prostate cancer vaccine". Reuters. 29 April 2010. Retrieved 2010-05-02.
  3. ↑ Berkrot, Bill (4 August 2011). "Dendreon plunges as Provenge prospects wither". Reuters. Retrieved 2011-08-04.
  4. ↑ "Dendreon files for Chapter 11 bankruptcy" (Press release). Reuters. 10 November 2014.
  5. ↑ "Valeant to sell Dendreon unit to China's Sanpower for $820 million". Reuters. 1 January 2017. Retrieved Mar 19, 2019.
  6. ↑ "Sanpower Group Completes the Acquisition of Dendreon from Valeant". PR Newswire. 29 June 2017.
  7. ↑ "BBC Global News." Interview by Julian King and Otis Brawley. GlobalNews (0400 GMT). BBC UK Podcast. London. 30 April 2010. Podcast.
  8. ↑ Rickman DS, Pflueger D, Moss B, et al. (April 2009). "SLC45A3-ELK4 is a novel and frequent erythroblast transformation-specific fusion transcript in prostate cancer". Cancer Research. 69 (7): 2734–8. doi:10.1158/0008-5472.CAN-08-4926. PMC   4063441 . PMID   19293179.
  9. ↑ Zylka MJ, Sowa NA, Taylor-Blake B, et al. (October 2008). "Prostatic acid phosphatase is an ectonucleotidase and suppresses pain by generating adenosine". Neuron. 60 (1): 111–22. doi:10.1016/j.neuron.2008.08.024. PMC   2629077 . PMID   18940592.
  10. ↑ Zimmermann H (March 2009). "Prostatic acid phosphatase, a neglected ectonucleotidase". Purinergic Signalling. 5 (3): 273–5. doi:10.1007/s11302-009-9157-z. PMC   2717315 . PMID   19322680.
  11. ↑ White KY, Rodemich L, Nyalwidhe JO, et al. (February 2009). "Glycomic Characterization of Prostate Specific Antigen and Prostatic Acid Phosphatase in Prostate Cancer and Benign Disease Seminal Plasma Fluids". Journal of Proteome Research. 8 (2): 620–30. doi:10.1021/pr8007545. PMC   2651839 . PMID   19128049.
  12. ↑ Erbas H, Erten O, Irfanoglu ME (December 2007). "Prostatic acid phosphatase in breast cyst fluid". The Malaysian Journal of Pathology. 29 (2): 95–9. PMID   19108401.
  13. ↑ Mungall D (March 2004). "rNAPc2 from Corvas. Nuvelo". Current Opinion in Investigational Drugs. 5 (3): 327–33. PMID   15083600.
  14. ↑ "Activated Cell Therapy Announces New Executive Management Team" (Press release). Activated Cell Therapy. 30 August 1995. Retrieved 30 June 2009.
  15. ↑ Small EJ, Fratesi P, Reese DM, et al. (1 December 2000). "Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells". Journal of Clinical Oncology. 18 (23): 3894–903. doi:10.1200/JCO.2000.18.23.3894. PMID   11099318.
  16. ↑ Timmerman, Luke (9 August 2006). "Building factory a balancing act for Dendreon". The Seattle Times . Retrieved 29 June 2009.
  17. ↑ Feuerstein, Adam (16 March 2007). "Dendreon's Date with Destiny". TheStreet.com. Archived from the original on 8 March 2008. Retrieved 29 June 2009.
  18. ↑ "US panel: Dendreon cancer therapy appears to work". Reuters. 29 March 2007. Retrieved 30 June 2009.
  19. ↑ Herper, Matthew (9 May 2007). "Dendreon's Dilemma". Forbes.com . Retrieved 9 May 2007.
  20. ↑ Pollack, Andrew (14 April 2009). "Promising Test for Dendreon's Prostate Cancer Drug". The New York Times . Retrieved 30 June 2009.
  21. ↑ "Dendreon Reports PROVENGE Regulatory and Commercialization Progress and Future Pipeline Plans at Analyst Event (NASDAQ:DNDN)". Archived from the original on 2011-07-09. Retrieved 2009-10-26.
  22. 1 2 "CNBC Article on Dendreonite Requests". Archived from the original on 2011-07-08. Retrieved 2009-05-01.
  23. ↑ Stein, Rob. "FDA Delay In Cancer Therapy Is Attacked". The Washington Post. Retrieved 2010-05-01.
  24. ↑ Roan, Shari (December 31, 2007). "Protest Descriptions". The Los Angeles Times.

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