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FDA Accepts Bristol Myers Squibb’s Supplemental New Drug Application for CAMZYOS
Bristol Myers Squibb declared that the U.S. FDA had accepted its supplemental new drug application for CAMZYOS for an expanded indication to reduce the need for septal reduction therapy. CAMYZOS is currently FDA-approved for treating adults with symptomatic New York Heart Association class II-III obstructive hypertrophic cardiomyopathy to improve functional capacity and symptoms.
“Currently, it is suggested that many patients suffering with severe symptomatic obstructive hypertrophic cardiomyopathy undergo septal reduction therapy. This often requires either an open-heart surgical procedure or septal ablation procedure, both are specialized care options,” added Roland Chen, MD, senior vice president and head of cardiovascular development, Global Drug Development at Bristol Myers Squibb. “For patients, the approval of CAMZYOS earlier this year was a crucial turning point. If the FDA approves the application for this additional indication, it might boost CAMZYOS’s reputation while also reaffirming our commitment to providing patients with transforming cardiovascular treatments.”
The sNDA submission was based on the results of Phase III VALOR-HCM study which is a randomized, double-blind, placebo-controlled study, which accessed CAMZYOS in patients with symptomatic, obstructive HCM who met the 2011 ACC/AHA guideline criteria for septal reduction therapy and who have been referred for an invasive procedure. VALOR-HCM met its primary and secondary endpoints with a high degree of statistical significance and no new safety signals observed.
VALOR-HCM is a randomized, double-blind, placebo-controlled, multicenter Phase III study of patients with symptomatic, obstructive HCM. They meet the guideline criteria for septal reduction therapy and have been referred for an invasive procedure. The study enrolled around 112 patients randomized on a 1:1 basis to receive mavacamten or a placebo. VALOR-HCM includes three treatment periods over a time duration of 128 weeks: a 16-week placebo-controlled period. During this 16-week active treatment period, all patients received mavacamten, and a 96-week long-term extension period where all patients received mavacamten.
Jazz and Zymeworks Sign Exclusive Licencing Agreement for Zanidatamab
Jazz Pharmaceuticals and Zymeworks declared that Jazz and Zymeworks’ subsidiary, Zymeworks BC, has entered into an exclusive licensing agreement under which Jazz will acquire development and commercialization rights to Zymeworks’ zanidatamab across all indications in the United States, Europe, Japan, and all other territories except for Asia-Pacific territories which are previously licensed by Zymeworks.
In various HER2-expressing tumors, zanidatamab, a HER2-targeted bispecific antibody with unique mechanisms of action, has demonstrated potent anticancer effect when used alone or in combination with other therapies. Current pivotal trials are testing zanidatamab as the first-line therapy for HER2-positive gastroesophageal adenocarcinoma and the second-line therapy for HER2-expressing biliary tract cancer. The U.S. Food and Drug Administration has given zanidatamab the Breakthrough Therapy designation for biliary tract cancer, a disease for which no HER2-targeted treatments are currently approved and establishing it as a potential first-in-class treatment. Based on Phase II data, zanidatamab combined with chemotherapy may be a best-in-class treatment.
Based on Zymeworks’ Azymetric technology, zanidatamab has the ability to attach to two HER2 non-overlapping epitopes simultaneously. A number of unique modes of action, including dual HER2 signal blocking, improved binding and removal of the HER2 protein from the cell surface, and potent effector function are produced by this creative design, which promotes anticancer activity in patients.
The FDA has given zanidatamab two Fast Track designations—one as a single drug for refractory biliary tract cancer and the other in combination with standard-of-care chemotherapy—for first-line GEA patients with HER2 gene-amplified biliary tract cancer who have previously received treatment. Due to these classifications, zanidatamab is qualified for Priority Review, Rolling Review, and Accelerated Approval, as well as FDA recommendations for a successful drug development program. Additionally, Zanidatamab has earned Orphan Drug designations from the European Medicines Agency for the treatment of gastric cancer and from the FDA for the treatment of biliary tract and gastric tumours.
Sumitomo Unit Agrees to Purchase Myovant After Raising Bid
After its initial offer was rejected, Sumitomo Pharma’s sweetened offer persuaded endocrinology specialist Myovant to agree to a takeover. Sumitomo and its subsidiary Sumitovant Biopharma initially offered USD 22.75 per share for Myovant, which develops hormonal therapies for conditions such as uterine fibroids, endometriosis, and prostate cancer, but this was deemed insufficient and was rejected earlier this month.
Now, a USD 27 per share offer has persuaded Myovant’s board to accept the offer, which comes nearly three years after Sumitomo purchased a 46% stake in Myovant as part of a strategic-level, USD 3 billion deal that formed Sumitovant from five Roivant group companies.
Sumitomo already owned approximately 52% of the company prior to the new offer, which values Myovant at approximately USD 2.9 billion, and is spending USD 1.7 billion to acquire 100% ownership of its shares. Myovant stated in a market update that the purchase price represents a 50% premium over its closing share price on September 30, the last day of trading prior to Sumitovant’s first offer.
Sumitomo will gain control of Myovant’s Pfizer-partnered oral GnRH antagonist Myfembree (relugolix), which was approved last year to treat uterine fibroids, as well as another formulation of the same drug called Orgovyx, which is used to treat prostate cancer, under the terms of the agreement, which is expected to close in the first quarter of 2023. In Myovant’s fiscal first quarter, which ended on June 30, 2022, sales of the two products were USD 4 million and USD 36 million, respectively.
AstraZeneca’s Tremelimumab Plus Imfinzi Combo Approves in the US
Tremelimumab, a CTLA4 inhibitor developed by AstraZeneca, has received regulatory approval as part of a combination therapy for advanced liver cancer. Tremelimumab was approved by the FDA in the United States for use in combination with AstraZeneca’s PD-L1 inhibitor Imfinzi (durvalumab) to treat adults with unresectable hepatocellular carcinoma (HCC), the most common type of liver tumor.
The CTLA4 inhibitor, now known as Imjudo, is only the second drug in the class to be approved, following Bristol-Myers Squibb’s well-known Yervoy (ipilimumab), which is used alongside BMS’ PD-1 inhibitor Opdivo (nivolumab) in a variety of solid tumors, including HCC and lung, colorectal, skin, and kidney cancers.
In previously untreated HCC patients, the FDA approved a single 300 mg dose of Imjudo given alongside 1,500 mg Imfinzi, followed by Imfinzi every four weeks – known as the STRIDE (single tremelimumab regular interval durvalumab) regimen.
AstraZeneca sees the first-line HCC indication as a significant opportunity for its immuno-oncology franchise, so it used a priority review voucher – typically valued at around USD 100 million – to reduce the FDA review time for the application to six months.
In the HIMALAYA trial, patients treated with the STRIDE regimen had a 22% lower risk of death compared to Nexavar, and nearly one-third of patients (31%) were still alive after three years, compared to 20% in the control group. The study defied the trend of tremelimumab, adding little or nothing to Imfinzi in various cancer types while increasing the side-effect burden of therapy. Yervoy is also known to be difficult to tolerate.
AbbVie Acquires DJS Antibodies for USD 255 Million in Cash
On October 20, 2022, AbbVie announced the acquisition of DJS Antibodies Ltd., a privately-held UK-based biotechnology company dedicated to discovering and developing the next generation of antibody therapeutics products that target difficult-to-drug disease-causing proteins, such as G protein-coupled receptors (GPCRs). As per the agreement, AbbVie will pay DJS shareholders approximately $255 million in cash at closing for the acquisition of DJS. Furthermore, AbbVie is planning to retain all current DJS employees and its facility in Oxford. Oxford Science Enterprises and Johnson & Johnson Innovation Ltd., along with LifeArc, Sedgwick Yard, and Amgen Ventures, are some of the founding investors backed by DJS.
DJS leverages a proprietary HEPTAD platform for the antibody discovery to GPCRs and other intractable targets. DJS-002 is one of the lead candidates of the DJS, the therapy is currently in the investigational preclinical studies. DJS-002 is a potential first-in-class lysophosphatidic acid (LPA) receptor 1 (LPAR1) antagonist antibody for the treatment of Idiopathic Pulmonary Fibrosis (IPF) and other fibrotic diseases. Moreover, upon achieving certain development milestones related to the DJS-002 program, the DJS shareholders remain eligible for potential additional payments.
AbbVie has a remarkable presence across several key therapeutic areas, such as immunology, oncology, neuroscience, eye care, virology, and gastroenterology. The latest acquisition of DJS Antibodies is expected to strengthen AbbVie’s immunology pipeline further. It will provide new capabilities to enhance AbbVie’s current antibody research activities and will expand the research efforts in the immunology segment.
Roche and Hookipa Pharma Signs USD 25 Million Deal for Arenaviral Immunotherapy
On October 20, 2022, HOOKIPA Pharma Inc. announced a strategic collaboration and license agreement with Roche to develop HB-700 for KRAS-mutated cancers and a second undisclosed novel arenaviral immunotherapy. HOOKIPA Pharma is a clinical-stage biopharmaceutical company developing a new class of immunotherapies based on its proprietary arenavirus platform. It is the first oncology licensing collaboration of HOOKIPA.
As per the update by HOOKIPA, through the collaboration, HOOKIPA will conduct research and early clinical development through Phase 1b for HB-700. HB-700 is a novel investigational arenaviral immunotherapy designed to treat KRAS-mutated lung cancer, colorectal cancer, pancreatic cancer, and other cancers. HB-700 is a replicating 2-vector therapy that targets the most common KRAS mutations: (G12D, G12V, G12R, G12C, and G13D) and thereby benefit more patients than single mutation inhibitors. Upon completing the Phase 1b trial, Roche has the right to assume development responsibility and commercialize licensed products across multiple indications after approval. The agreement also includes an option for Roche to license second arenaviral cancer immunotherapy.
Furthermore, HOOKIPA will get a $25 million upfront payment per the contract terms. HOOKIPA will earn an extra $15 million payment upon the option exercise if Roche chooses to extend the first agreement by adding a new product candidate. Including this option payment, HOOKIPA is qualified for research, development, and commercialization milestone-based payments totaling approximately $930 million. Upon commercialization, HOOKIPA is eligible to receive tier-based royalties on the global net sales of HB-700 and the additional product candidate that range from a high single-digit to a mid-teens percentage.