MedNess: bite-size biopharma and medtech news

Novartis’ Kymriah hits roadblock in 2^nd line B-cell aNHL
On 24^th August, Novartis announced that Kymriah (tisagenlecleucel, CD19- targeting CAR-T) failed to meet the primary endpoint of event-free survival (EFS) in the pivotal Phase 3 BELINDA trial patients with aggressive B-cell non-Hodgkin lymphoma (NHL) after relapse or lack of response to frontline therapy. 
Background: HDCT followed by SCT is considered the gold standard for patients with aggressive B-cell NHL. However, the therapy is very intense with considerable side-effects and is not curative. Thus, there is a significant unmet need for newer, better therapies for patients with R/R LBCL. ​
Details: The BELINDA trial evaluated Kymriah as second line therapy, against SoC (salvage platimun-based chemotherapy followed by high dose chemotherapy and autologous HSCT in responding patients), in patients with either primary refractory aggressive B-cell NHL or relapse within 12 months of frontline treatment (rituximab and anthracycline containing regimen).
The trial did not show clinically meaningful benefit in the primary endpoint of EFS versus the SoC. Although, the safety profile of Kymriah remained consistent with previous findings.
Novartis and trial investigators will complete a detailed assessment of results and present data at an upcoming meeting.
Kymriah was the first CAR-T to be approved in 2017; its current approved indications included R/R ALL and 3L+ DLBCL where it has demonstrated significant efficacy and favourable safety profile based on RCTs and RWE in over 5,300 patients.
Implications: Kymriah’s failure to show significant improvements in EFS in 2L aNHL flails Novartis’ aspirations of market expansion in this therapy area. Earlier, the company had reported positive results in R/R follicular lymphoma from the registrational Phase 2 ELARA trial; submissions are expected in H2 2021. 
In June, Gilead and BMS reported statistically significant improvements in EFS (primary endpoint) in 2^nd line in similar settings for their CAR-T therapies. Gilead’s Yescarta demonstrated 40% improvement in EFS in the ZUMA-7 trial with potential sBLA/MAA filings in 2H21. BMS’ Breyanzi also met the primary endpoint of EFS in TRANSFORM trial. All three CAR-Ts are approved for 3L+ DLBCL, although Breyanzi in the new entrant in this space.
Laurent Flamme, an analyst with ZKB, noted, “With a positive outcome, the consensus for peak sales would probably have gone above $2 billion from currently a little over $1 billion. With the approved indications, however, $1 billion in peak sales is still possible.”

FDA Approves TIBSOVO® (ivosidenib tablets) in IDH1-Mutated Cholangiocarcinoma
"Servier has been focused on exploring the significant potential of inhibiting mutant IDH enzymes as a novel approach to treating cancers with high unmet needs, including cholangiocarcinoma," said David K. Lee, CEO, Servier Pharmaceuticals. "We are proud to bring to patients the first and only targeted therapy for previously treated IDH1-mutated cholangiocarcinoma. We are grateful to the patients, caregivers, investigators and study teams who made this achievement possible through their participation in the ClarIDHy clinical trial."

US accelerated approval for Tecentriq® + Abraxane® in PD-L1+ve mTNBC withdrawn
“TNBC remains the most challenging type of breast cancer to treat, which makes the decision to withdraw so difficult for us, as patients have had this medicine as an important option for more than two years,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We appreciate the opportunity to have been able to help people with mTNBC in the US with Tecentriq through the accelerated approval process, which has brought many significant and novel therapies to patients. We remain dedicated to finding meaningful treatments for people living with this aggressive disease and will continue to study Tecentriq in mTNBC.”

Shape Therapeutics collaborate with Roche to advance RNA technologies in gene therapy
On 24th August, Shape Therapeutics announced that it has entered into strategic research collaboration with Roche to advance the gene therapy space.  Shape Therapeutics will utilize its proprietary RNA editing platform RNAfix™ and potentially leverage its AAV (adeno-associated viruses)-based RNA editing technology platform, AAVid™ for next-generation tissue-specific AAVs for the development of gene therapy for certain targets in the areas of Alzheimer’s disease, Parkinson’s disease, and rare diseases.

Lung cancer screening made non-invasive using AI
Lung cancer happens to be one of the subtypes of malignant diseases where an early detection is rare, but can tremendously improve patient survival. Only less than 6 percent pf high risk individuals go through the low-dose computed tomography screening that has the potential to save thousands of lives. Exposure to radiation, cases of false positive, and aversion towards invasive techniques remain as the main reason for the lower level of screening. A novel artificial intelligence blood testing technology developed by Johns Hopkins Kimmel Cancer Center shows a new avenue to detect lung cancer at an early stage. The technique called DELFI (DNA evaluation of fragments for early interception) is designed to identify unique patterns in the fragmentation of DNA shed from cancer cells within the bloodstream. In a study that utilized 796 individual blood samples from Denmark, the Netherlands, and the United States, the AI program was successful in differentiating between presence or absence of lung cancer.  According to the lead author of the study Dimitrios Mathios  “It is clear that there is an urgent, unmet clinical need for development of alternative, noninvasive approaches to improve cancer screening for high-risk individuals and, ultimately, the general population.” According to him, “We believe that a blood test, or ‘liquid biopsy,’ for lung cancer could be a good way to enhance screening efforts, because it would be easy to do, broadly accessible and cost-effective.” By using machine learning tools, the study identified abnormal patterns in DNA sequence within the cell-free DNA released in the blood stream by dead or dying cells. This study of “fragmentome” is a low-cost technology that reliably differentiated between cancer developing population by identifying a wide variation in their fragmentome profiles, while those who didn’t have cancer had consistent fragmentome profiles.