Novo Nordisk discontinued two Phase III studies and one Phase II trial in March 2020 after three patients developed non-fatal blood clots. The FDA also put the initiative on hold for clinical trials. However, Novo restarted development in August 2020 after discovering a “new way forward.”
The company plans to file for approval of concizumab in the United States and Japan before the end of this year and in Europe in 2023. Concizumab, according to the company, has the potential to be a USD 1 billion-plus drug.
AbbVie Pulls its Alliance with Alector For Alzheimer’s Disease Candidate AL003
AbbVie has ended its collaboration with Alector on the development of Alzheimer’s disease candidate AL003, which attempts to treat the neurodegenerative disease by restoring decreased immune system activation in the brain.
In 2017, AbbVie began a partnership with Alector, paying USD 205 million upfront for exclusive rights to two therapeutic concepts. The agreement represents a departure from the prevalent amyloid hypothesis, which has been the target of numerous Alzheimer’s drug candidates who have attempted and failed to combat the disease over the previous 25 years but remains the primary focus of drug development for the condition.
Late last year, Alector presented Phase I data on one of the candidates, AL003, in healthy volunteers, demonstrating that the candidate is well tolerated up to once-monthly intravenous doses of 15 mg/kg and engages the transmembrane receptor CD33 in both blood and central nervous system compartments. SIGLEC 3 is an inhibitory receptor found largely on myeloid lineage cells such as microglia, which are part of the brain’s immune system. Based on the data, Alector, which is in charge of developing and carrying out Phase I and II studies, has planned to advance to the next stage of development in the second half of 2022.
Now that the study is complete, AL003 has been discarded, dealing a blow to one of the few alternative avenues for Alzheimer’s therapy that drug developers are pursuing. It will also sever Alector’s possible future revenue stream from the alliance, which includes up to USD 986 million in option and milestone payments.
ADC Therapeutics and Sobi Enters in Exclusive Licensing Deal to Develop and Commercialize Zynlonta
ADC Therapeutics announced that it took up an exclusive license agreement with Swedish Orphan Biovitrum AB for the development and commercialization of Zynlonta for all hematologic and solid tumor indications outside of the United States, greater China, Singapore and Japan. The Marketing Authorization Application for Zynlonta was validated by the European Medicines Agency at the end of October 2021, and orphan drug designation was granted for Zynlonta for the diffuse large B-cell lymphoma treatment in Europe. ADC Therapeutics and Sobi intend to make Zynlonta available following a regulatory decision that is expected by the first quarter of 2023. In the agreement clause, ADC Therapeutics is liable to receive an upfront payment of USD 55 million, and is also eligible to receive USD 50 million upon regulatory approval of Zynlonta in third-line DLBCL by the European Commission and up to approximately USD 330 million in additional regulatory and sales milestones.
On April 2021, an accelerated approval was granted to Zynlonta by the US FDA as the first and only CD19-targeted ADC as a single-agent treatment for adult patients with relapsed or refractory DLBCL after two or more lines of systemic therapy. ADC Therapeutics also dealt with Mitsubishi Tanabe Pharma Corporation and signed an exclusive license agreement for the development and commercialization of Zynlonta for all hematologic and solid tumor indications in Japan.
BMS’ Opdivo Gets NHS Use as Adjuvant Bladder Cancer Treatment
NICE recommended routine use of Bristol-Myers Squibb’s Opdivo for the adjuvant treatment of patients with urothelial carcinoma considered to be the most common form of bladder cancer. The guidance allows Opdivo (nivolumab) to be used after surgery in patients with muscle-invasive UC who are at high risk of the cancer coming back, and whose tumours express PD-L1 at a level of 1% or more. It is only recommended for patients who cannot be treated with adjuvant platinum-based chemotherapy. Currently, more than 50% of patients with bladder cancer will experience recurrence after surgery, and the disease kills nearly 200,000 patients worldwide every year.
The green flag makes Opdivo a second immunotherapy option for NHS patients with this form of cancer after Roche’s Tecentriq (atezolizumab), which can currently be used as an alternative to chemo in untreated locally advanced or metastatic UC expressing PD-L1 at a level of 5% or more. NICE based its decision on the results of the Phase 3 CheckMate-274 study, which showed that almost 68% of patients treated with Opdivo after surgical resection of their tumour were still alive and disease-free 12 months later, compared to 46% of those receiving placebo.
Opdivo was approved in Europe for use as an adjuvant therapy for urothelial carcinoma earlier this year, its third post-surgery indication after melanoma and oesophageal/gastroesophageal junction cancer. Securing approvals in the adjuvant or neoadjuvant setting is a key strategy for BMS and other checkpoint inhibitor developers, as it allows them to position their immunotherapies as early as possible in the treatment pathway.
AstraZeneca Signs USD 1.3 Billion Deal to Acquire TeneoTwo
AstraZeneca declared that the company had acquired TeneoTwo, including the phase I clinical-stage CD19/CD3 T-cell engager, TNB-486, which is presently under evaluation in relapsed/refractory B-cell non-Hodgkin lymphoma.
The acquisition of TNB-486 aims to advance the development of the potential new medicine for B-cell hematologic malignancies, which includes diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. Building on the success of Calquence, TNB-486 additionally expands into AstraZeneca’s hematology pipeline that spans various therapeutic modalities and mechanisms to address a broad category of blood cancers.
T-cell engagers are molecules designed to drive the T-cells of the immune system to identify and eradicate cancer cells. TNB-486 activates and recruits T-cells to CD19-expressing tumors, where they can elicit an immune response by binding to both CD19 and to the CD3 receptor on T-cells.
AstraZeneca will acquire all the outstanding shares of TeneoTwo in exchange for an upfront payment of $100m.
Under the agreement terms, AstraZeneca will make additional contingent R&D-related milestone payments of up to $805m and other contingent commercial-related milestone payments of up to $360m to TeneoTwo’s equity holders.
The transaction will close in the 3rd quarter of 2022, subject to customary closing conditions and regulatory clearances. The transaction does not impact AstraZeneca’s financial guidance for 2022.
FDA Grants Orphan Drug Designation to PBI-200 for NTRK Fusion–Positive Solid Tumors
The FDA granted an orphan drug designation to PBI-200 for the treatment of patients suffering with NTRK fusion-positive solid tumors, comrising primary and metastatic brain tumors.
Preclinical studies in intracranial xenograft models demonstrated that PBI-200 offered high efficiency and a manageable safety profile in comparison to other TRK inhibitors.
PBI-200 will undergo evaluation in the phase I/II PBI-200-101 trial in patients suffering with NTRK fusion-positive advanced/metastatic tumors, comprising primary and metastatic central nervous system (CNS) tumors. The trial is comprised of a dose-escalation phase and multicohort expansion at the recommended phase II dose.
In phase I, patients will be required to have EWSR1 WT1–positive desmoplastic small round cell tumors. Those with NTRK fusion-positive solid tumors other than primary brain tumors are required to have received prior treatment with a TRK inhibitor unless the patient did not have access to treatment with a TRK inhibitor. Patients with NTRK-amplified solid tumors, primary brain tumors, or EWSR1 WT1–positive DSRCTs may have received prior treatment with a TRK inhibitor, although it is not required.
Key exclusion criteria include having received treatment with cytotoxic chemotherapy, a biologic agent, an investigational agent, or radiation therapy within three weeks of the first dose of PBI-200; or having received treatment with small molecule kinase inhibitors or hormonal agents within 14 days and five half-lives prior to the first dose of PBI-200.
Notably, patients with either primary brain tumors or brain metastasis must have completed brain radiation 12 weeks prior to the trial’s baseline brain MRI, which will be performed four weeks before the first dose of PBI-200.
The primary endpoints of the phase I portion of the trial include examining adverse effects and establishing the RP2D of the investigative agent. Secondary endpoints include the area under the plasma drug concentration-time curve after one dose and 28 doses, overall response rate (ORR), duration of response, and progression-free survival.
In phase 2 of the trial, ORR will serve as the primary endpoint in each cohort examined.
Merck to Acquire Seagen for Nearly USD 40 Billion
In one of the latest commercial updates in the healthcare industry, Merck is set to acquire Seagen for nearly USD 40 Billion. Merck will present the second-quarter earnings report on July 28, 2022, and both companies are hoping to finalize the deal before that. Merck is expected to pay above $200 per share. The acquisition talk started in late June and is expected to be completed within the next few weeks.
Both the parties are in the advanced stages of completing the deal, which could be the world’s largest biopharma acquisition since 2020. Earlier in June 2019, AbbVie announced the purchase of Allergan for $63 billion. AstraZeneca bought the rare disease specialist Alexion for a $39 billion deal in 2021.
Seagen, previously known as Seattle Genetics, is one of the largest biotechnology companies in the USA, focussing on developing and commercializing innovative, empowered monoclonal antibody-based therapies for cancer treatment. The company has delivered several transformative cancer therapies.
Merck has several world’s best-selling cancer drugs, including its PD-1 inhibitor Keytrudal. Seagen’s acquisition is expected to further bolster Merck’s presence in the oncology segment. Merck will tap Seagen’s industry-leading ADC technology.
FDA Grants Priority Review to Roche’s T-cell Engager Lunsumio For Follicular Lymphoma Treatment
The FDA has granted a priority review to Roche’s T-cell engager Lunsumio as a treatment for follicular lymphoma (FL). Lunsumio® (mosunetuzumab) could be the first FDA-approved CD20xCD3 T-cell engaging bispecific antibody for the treatment of any type of non-Hodgkin lymphoma. Lunsumio is being studied for other indications, including follicular lymphoma, diffuse large B-cell lymphoma, and other blood cancers.
The phase I/II study result has induced high and durable complete response rates, which has played a pivotal role in granting the Priority Review designation. A robust clinical development program for Lunsumio is ongoing, investigating the molecule as a monotherapy and in combination with other medicines.
Lunsumio (mosunetuzumab) has already been approved in the EU for that indication based on the results of a phase 1/2 study. The Lunsumio has shown an overall response rate of 80% and a median progression-free survival of around 18 months when used as a third-line or later therapy. If approved by the FDA, Lunsumio is expected to offer an off-the-shelf alternative to CAR-T therapies like Gilead Sciences’ Yescarta (axicabtagene ciloleucel) and Novartis’ Kymriah (tisagenlecleucel).
In the United States, nearly 13,000 new cases of FL will be diagnosed in 2022. The launch of the therapy, Lunsumio, is expected to improve the Follicular Lymphoma treatment scenario in the coming years.
