Date: 2013-12-17
Type of information: Granting of a Market Authorisation in the US
Product name: Beleodaq™
Compound: belinostat
Therapeutic area: Cancer - Oncology
Action mechanism: histone deacetylase inhibitor. Belinostat is a small molecule HDAC inhibitor being investigated for its role in the treatment of a wide range of solid tumors and hematologic malignancies either as a single agent, or in combination with other active anti-cancer agents, including carboplatin, paclitaxel, doxorubicin, idarubicin, cis-retinoic acid, azacytidine, 5-FU, etoposide and bortezomib for injection. HDAC inhibitors represent a new mechanistic class of anti-cancer therapeutics that target HDAC enzymes, and have been shown to: Arrest growth of cancer cells (including drug-resistant subtypes); induce apoptosis, or programmed cell death; promote differentiation; inhibit angiogenesis; and sensitize cancer cells to overcome drug resistance when used in combination with other anti-cancer agents.
Company: Topotarget (Denmark), now Onxeo (France) - Spectrum Pharmaceuticals (USA - CA)
Disease: peripheral T-cell lymphoma (PTCL)
Latest news: * On July 3, 2014, the FDA approved Beleodaq® (belinostat) for the treatment of patients with peripheral T-cell lymphoma (PTCL), a rare and fast-growing type of non-Hodgkin lymphoma (NHL). The action was taken under the agency’s accelerated approval program. “This is the third drug that has been approved since 2009 for the treatment of peripheral T-cell lymphoma,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. The FDA granted accelerated approval to Folotyn® (pralatrexate - Spectrum Pharmaceuticals) in 2009 for use in patients with relapsed or refractory PTCL and Istodax® (romidepsin - Celgene) in 2011 for the treatment of PTCL in patients who received at least one prior therapy.
The safety and effectiveness of Beleodaq® was evaluated in a clinical study involving 129 participants with relapsed or refractory PTCL. All participants were treated with Beleodaq® until their disease progressed or side effects became unacceptable. Results showed 25.8 percent of participants had their cancer disappear (complete response) or shrink (partial response) after treatment. The most common side effects seen in Beleodaq®-treated participants were nausea, fatigue, fever (pyrexia), low red blood cells (anemia), and vomiting.
This NDA approval triggers a milestone cash payment of $ 25 million from Spectrum Pharmaceuticals. A double-digit royalties as well as sales milestones of the aggregated net sales will be received by the company.
* On February 6, 2014, Topotarget has announced that the FDA has granted acceptance to file and Priority Review for the Beleodaq™ NDA for the treatment of relapsed or refractory PTCL. The FDA decision date based on PDUFA is set for August 9, 2014. In December 2013, Topotarget's US partner, Spectrum Pharmaceuticals, submitted a NDA for belinostat in relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL) to the FDA. The acceptance to file triggers the first of two expected milestone payments related to the study of BeleodaqTM in R/R PTCL patients in the USA: Spectrum Pharmaceuticals is to pay Topotarget $ 10 million and 1 million Spectrum Pharmaceuticals shares. As previously disclosed, an additional milestone cash payment from Spectrum Pharmaceuticals is triggered upon an NDA approval. Upon an approval, Topotarget will moreover be eligible to receive potential royalty payments and sales milestones.
* On December 10, 2013, Topotarget has announced the submission of a New Drug Application (NDA) for belinostat for the treatment of relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL) to the FDA. The NDA has been filed for Accelerated Approval with a request for Priority Review. Response from the FDA regarding acceptance to file is expected within 60 days from the FDA receipt date.The NDA for belinostat for the treatment of R/R PTCL in the USA has been submitted to the FDA by Topotarget US partner Spectrum Pharmaceuticals. The application is filed for Accelerated Approval with a request for Priority Review. Potential acceptance to file and decision of Priority Review grant from the FDA is expected within 60 days from the FDA receipt date. If the FDA grants acceptance to file the NDA for belinostat in this indication, a potential Accelerated Approval of the NDA can take place within 8-12 months from the FDA receipt date. The application is based on the CLN-19 BELIEF study and potentially entails two significant milestones during 2014. The first milestone relates to the acceptance to file from the FDA: Upon acceptance, Topotarget is entitled to receive a cash payment of $ 10 million from Spectrum Pharmaceuticals as well as 1 million Spectrum Pharmaceuticals shares (equal to approximately $ 9.4 million). The second milestone matures upon FDA approval of the NDA upon which Spectrum Pharmaceuticals will make a cash payment of $ 25 million to Topotarget.
* On August 7, 2013, Spectrum Pharmaceuticals announced that the filing of the New Drug Application (NDA) for belinostat in peripheral T-cell lymphoma (PTCL) has been postponed to Q4 2013. This delay causes a postponement of the first milestone payment from Spectrum Pharmaceuticals and hence changes Topotarget’s financial outlook for the year. Topotarget now expects an estimated pre-tax loss in the range of DKK 46-51 million for the full-year financial result for 2013 (compared to the previous outlook which was a pre-tax profit DKK 49-54 million). The expected net cash and cash equivalents will be around DKK 22-27 million at year-end 2013 (compared to the previously estimated DKK 114-119 million). Topotarget is entitled to receive 1 million shares in Spectrum Pharmaceuticals and a $ 10 million milestone upon acceptance to file by the FDA. Topotarget is moreover entitled to receive a milestone cash payment in the form of $ 25 million upon approval of the NDA by the FDA. The first milestone is expected during Q1 2014 and the second during H2 2014.
The reason for this postponement is that a pre-NDA meeting has taken place at which the FDA was specific as to what kind of information and which data format should be included in the belinostat NDA. The pre-NDA meeting was requested as it is essential for Topotarget and Spectrum Pharmaceuticals to submit an NDA of high quality. Our companies have therefore been in continuous dialogue with the FDA in order to align expectations and demands. Topotarget is cooperating with Spectrum Pharmaceuticals in order to facilitate the process as diligently as possible. At this point, the NDA is being fine-tuned in order to ensure a smooth way forward.
* On September 4, 2012, the COMP has adopted a positive opinion recommending belinostat for designation as orphan medicinal products for the treatment of peripheral T-cell lymphoma (nodal, other extranodal and leukaemic/disseminated).
Patents: * On November 21, 2013, Topotarget has announced that the European patent covering Composition of Matter for belinostat (EP01970011) has been granted. This application has claims covering belinostat itself and its use in proliferative diseases including cancer. The ensuing patent will protect the compound until at least 2021, with the possibility of protection up to 2026, from associated Supplementary Protection Certificates. Similar patents have already been granted in other major territories including the US and Japan. The total patent estate covering belinostat compositions, formulations, methods of use, and methods of manufacture cover the clinical use of this drug out to 2030 and beyond.
Submission of marketing authorization application USA : 2013-12-10
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2014-07-03
UE authorization:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA: 2009-09-03 (Spectrum Pharmaceuticals)
Orphan status UE: 2012-10-10
Pediatric exclusivit _USA:
Pediatric exclusivity UE: OTC status: Other news: • On April 24, 2017, Clinigen Group plc’s Idis Managed Access (MA) division and Onxeo have agreed to launch a Managed Access programme for belinostat (Beleodaq®) in Europe. Belinostat is for use in patients with relapsed or refractory peripheral T-cell lymphoma. This form of blood cancer is comprising of a group of rare and aggressive non-Hodgkin lymphomas (NHL), a malignant lymphoproliferative disorder. PTCL accounts for approximately 10%-15% of all NHL cases. There are no approved treatments for PTCL in Europe. The programme will be launched in United Kingdom, Germany, France, Spain, Italy, Denmark, Sweden, Norway, Finland, Belgium, The Netherlands, Luxembourg, and Austria.
The programme allows physicians to request belinostat for individual patients for whom alternative treatment options are not currently available. This enables patients on a named patient basis in Europe to benefit from belinostat treatment ahead of a potential European approval.
