MedNess: bite-size biopharma and medtech news

MacroGenics’ Margenza failed to show OS benefit in the Phase 3 trial for HER2+ mBC
On 7^th September, MacroGenics announced that the final analysis of Phase III SOPHIA trial investigating Margenza + chemotherapy did not show statistically significant improvement in overall survival over trastuzumab + chemotherapy in overall patient population with HER2+ metastatic breast cancer (mBC).
Background: In December 2020, Margenza was approved by the US FDA for the treatment of patients with HER2+ mBC after progression on two or more anti-HER2 regimens, including at least one regimen for metastatic disease. The drug was approved, primarily based on 24% risk reduction is disease progression or death compared to trastuzumab + chemotherapy (mPFS: 5.8 vs. 4.9 months, p=0.033) and confirmed ORR of 22% vs. 16%.
Details: The SOPHIA trial evaluated Margenza + chemotherapy vs. trastuzumab + chemotherapy in 536 HER2+ mBC patients with 2 prior lines of anti-HER2 treatment including a systemic treatment. The final OS analysis, one of the co-primary endpoints of the trial, included 385 events in the ITT population and did not demonstrate statistical significance (mOS: 21.6 vs. 21.9 months, p=0.62) versus the comparator arm.
However, in a subgroup of patients homozygous for F-allele at CD16A 158F, consisting nearly 40% of study population, Margenza arm showed 28% improvement in OS over trastuzumab arm (mOS: 23.6 vs. 19.2 months, p=0.05). While, in subgroups of CD16A F/V and CD16A V/V patients, treatment with trastuzumab resulted in better overall survival. The safety profile was consistent with the one previously reported for Margenza and consistent with the FDA label.
MacroGenics will submit these data to the FDA and present at a future congress.
Implications: Additional studies will be needed to evaluate the impact of Margenza in HER2+ BC with different CD16A allelic variants. It remains to be seen if the FDA will now restrict the all-comers label of Margenza to a specified patient population, especially since trastuzumab overperformed in certain patient subgroups. As per Stifel analysts, genotype-directed prescribing was already happening for Margenza. According to the SVB Leerink analyst, projected Margenza 2028 sales in the currently approved indication would be a mere $94 million.

KEYTRUDA® + chemotherapy Approved in China in 1L Locally Advanced Unresectable or Metastatic Esophageal or GEJ Carcinoma patients
 “In China, esophageal and gastroesophageal junction cancers are leading causes of death, and there have been few treatment advances for patients over the past several decades,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “With this approval of KEYTRUDA plus chemotherapy – the first for an anti-PD-1 regimen in the first-line setting – we can now provide patients with an immunotherapy treatment option earlier in the course of treatment that has been shown to significantly improve survival.”

FDA Grants Breakthrough Device Designation to the NovoTTF-200T™ System for Advanced Liver Cancer
“We are very pleased that the FDA has granted breakthrough designation for Tumor Treating Fields together with atezolizumab and bevacizumab to treat advanced liver cancer,” said Asaf Danziger, Novocure’s CEO. “Our data suggest that TTFields have the potential to extend survival in this particularly aggressive disease. We are working closely with trial investigators and intend to initiate a randomized controlled trial studying TTFields in combination with atezolizumab and bevacizumab as soon as possible.”

Enrollment Completed in Ph 3 Trial of CAN-2409 + Valacyclovir for the Treatment of Intermediate-High Risk Localized Prostate Cancer
“The combination of CAN-2409 with radiation therapy has been shown to create an immune stimulatory environment and is designed to activate the body's immune system to recognize and destroy cancer cells,” said Paul Peter Tak, M.D., Ph.D., FMedSci, President and Chief Executive Officer of Candel Therapeutics. “There is a significant need in patients with localized, non-metastatic prostate cancer for novel therapies that will improve outcomes, while reducing the need for long-term androgen deprivation therapy with its associated side effects. We believe CAN-2409 could improve disease outcome in patients with prostate cancer, and we look forward to the results of this potentially registrational clinical trial in 2024.”

Astellas Pharma voluntarily halts clinical trial for X-linked Myotubular Myopathy
On 1^st September, Astellas Pharma announced that it has voluntarily paused the screening and dosing of additional participants in its ASPIRO clinical trial evaluating AT132 in patients with X-linked Myotubular Myopathy. This is following a serious adverse event in a study participant due to abnormal liver function tests observed in the weeks following dosing of the AT132 investigational gene therapy. AT132 is an AAV8 vector containing a functional copy of the human MTM1 (myotubularin) gene. Earlier in December 2020, the ASPIRO clinical trial was put on hold when three children died after receiving a high dose of AT132, with each experiencing liver problems.
On 14th September, Astellas provided an update that the patient passed away on 9th September and the cause of death is yet to be known. Any serious outcomes of the trial will be taken into consideration to proceed safely with the ASPIRO trial.

GeneQuine and Exothera enter gene therapy development partnership
GeneQuine Biotherapeutics has entered into collaboration with Exothera, a full-service Contract Development and Manufacturing Organization. This is to conduct a feasibility study for the development of a large-scale manufacturing process for GeneQuine’s osteoarthritis gene therapy product candidate GQ-303, in the highly scalable scale-X™ fixed-bed bioreactor. GQ-303 is an intra-articular gene therapy candidate, which turns joint cells into factories for production of the therapeutic protein proteoglycan 4. Exothera will perform a feasibility study with the small-scale version of the scale-X bioreactor to assess the suitability of the platform for production of GQ-303 and GeneQuine’s other product candidates.

Airway Therapeutics Doses First Patient with Novel COVID-19 Treatment
Airway Therapeutics, a start-up spun out from Cincinnati Children’s Hospital in 2011 is developing a treatment of lung disease for patients critically ill with COVID-19. The company has started clinical trials for its novel treatment AT-100.
In August, Airway dosed its first patient with AT-100 - an engineered protein that reduces inflammation and infection in the body as a part of a phase 1b trial to determine the safety and tolerability of the treatment. The company says that AT-100 has the potential to reduce injuries resulting from being ventilated in COVID-19 patients and also help prevent secondary infection; inhibit viral replication; and promote viral elimination in severely ill, ventilated COVID-19 patients.
According to the company, the patient is much improved and has been extubated since the protein was administered. Airway plans to enroll eight other patients in the trial.
Airway had initially developed AT-100 for the prevention of bronchopulmonary dysplasia (BPD) in preterm infants. When the pandemic hit, the start-up realized the protein’s anti-inflammatory and anti-infective properties made it potentially effective against COVID-19.
 

Immatics Biotechnologies Gets 4 Patent for T cell receptors and Combination of Peptides for Use in Immunotherapy Against Small Cell Lung Cancer, PRAME positive cancer and Other Cancers
On Sept 10, 2021; Immatics Biotechnologies has received a patent for peptides and a combination of peptides for use in immunotherapy against small cell lung cancer and other cancers. patient’s own T cells are genetically modified to express a novel proprietary TCR cognate to one of Immatics’ cancer targets and are then reinfused. This approach is also known as TCR-T (T cell receptor T cell). The product class ACTallo® is advancing the ACT concept beyond individualized manufacturing and is being developed to generate “off-the-shelf” cellular therapy. This invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.
Immatics Biotechnologies is a Tubingen-based midsize Biotech company with 300 team members and 200+ targets covering solid and liquid tumors. They have 2 proprietary technology Platforms and 7 programs.