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MedNess: bite-size biopharma and medtech news

15th January, 2020
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MedNess This Week

HIGHLIGHTS
Our Sponsors
MedNess wishes it's readers

**A very happy and productive 2020!!**
 
We are very grateful for your support in 2019 and look forward to more MedNess-ing in 2020 and beyond.
Drug Approval
Enhertu (trastuzumab deruxtecan) approved in the US for 3L+ HER2-positive unresectable or metastatic breast cancer patients based on Ph II DESTINY-Breast01 trial data
José Baselga, Executive Vice President, Oncology R&D, said: “Enhertu has shown impressive results in women with HER2-positive metastatic breast cancer, with the majority of women benefiting from treatment and the median duration of the response exceeding 14 months. With this first approval, we are proud to bring Enhertu to patients with high unmet need and we look forward to further exploring its potential in additional settings.”
FDA grants accelerated approval to PADCEV™ (enfortumab vedotin-ejfv) in locally Advanced or metastatic urothelial cancer patients
“The FDA approval of PADCEV is welcome news for patients with bladder cancer,” said Andrea Maddox-Smith, Chief Executive Officer, Bladder Cancer Advocacy Network. “Though new medicines for bladder cancer have been approved in recent years, most people living with advanced stages of this disease face a difficult journey with few treatment options.”
Lynparza approved in the US in 1L maintenance treatment of gBRCA-mutated metastatic pancreatic cancer based on Ph III POLO trial results
Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: “Patients with advanced pancreatic cancer historically have faced poor outcomes due to the aggressive nature of the disease and limited treatment advances over the last few decades. Lynparza is now the only approved targeted medicine in biomarker-selected patients with advanced pancreatic cancer.”
Click Here for more Drug Approvals
Regulatory News
FDA accepts NDA, grants Priority Review to UGN-101, potentially the first non-surgical therapy for the treatment of Low-Grade Upper Tract Urothelial Cancer (LG UTUC)
“The FDA filing acceptance and granting of priority review for UGN-101 is an important milestone in our mission to pioneer new treatments to improve patient care in specialty cancers and urologic diseases,” said Liz Barrett, President and Chief Executive Officer of UroGen. “There is a significant unmet need for a better treatment option for patients with LG UTUC, as the current standard of care involves surgical removal of the kidney or repetitive endoscopic tumor removal.”
FDA accepts sNDA and grants priority review to BRAFTOVI® (encorafenib) + ERBITUX® (cetuximab) (BRAFTOVI Doublet) based on results from the Ph III BEACON CRC trial
“The FDA’s acceptance of our application for the BRAFTOVI Doublet is highly encouraging news for patients with mCRC harboring a BRAFV600E mutation,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. “Currently, there are no FDA-approved treatments specifically for patients with BRAF-mutant mCRC who have received prior treatment. If approved, the BRAFTOVI Doublet would become the first targeted regimen for this patient population, who typically have a poor prognosis. We also look forward to continuing to explore this targeted Doublet regimen with or without MEKTOVI in earlier lines of BRAF-mutant mCRC, including in the ongoing, Phase 2 ANCHOR study in previously untreated patients.”
BCMA CAR-T Therapy JNJ-4528 granted U.S. FDA Breakthrough Therapy Designation for the treatment of Relapsed or Refractory Multiple Myeloma
"The granting of Breakthrough Therapy Designation for JNJ-4528 is a significant milestone as we continue to accelerate the global development of this innovative CAR-T therapy in collaboration with Legend Biotech," said Sen Zhuang, M.D., Ph.D., Vice President, Oncology Clinical Development, Janssen Research & Development, LLC. "We look forward to continuing to work closely with the U.S. Food and Drug Administration to advance the clinical development program for JNJ-4528 and ultimately bring this BCMA-targeted immunotherapy to patients living with multiple myeloma who are in need of a new therapeutic option."
FDA grants Breakthrough Therapy Designation for Tucatinib in locally advanced or metastatic HER2-positive Breast Cancer based on HER2CLIMB trial results
“The addition of tucatinib to the commonly used combination of trastuzumab and capecitabine demonstrated superior activity compared to trastuzumab and capecitabine alone in patients with unresectable locally advanced or metastatic HER2-positive breast cancer, including those with and without brain metastases,” said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. “The decision by the FDA to grant Breakthrough Therapy designation to tucatinib recognizes the urgent need for new medicines that can impact the lives of those with HER2-positive metastatic breast cancer. We intend to submit a New Drug Application to the FDA and an MAA to the EMA by the first quarter 2020, with the goal of making tucatinib available to patients in this setting as soon as possible.”
Click Here for more Regulatory News
Trial Results
Ph III IMspire150 trial of Tecentriq® (atezolizumab) + Cotellic® (cobimetinib) and Zelboraf® (vemurafenib) met primary endpoint of PFS improvement in 1L BRAF V600 mutation-positive advanced melanoma patients
“By combining a cancer immunotherapy with targeted therapies, we hope to offer a new approach that improves outcomes for people with advanced, BRAF-mutant melanoma." said Levi Garraway, M.D., Ph.D., Chief Medical Officer and Head of Global Product Development. "We look forward to discussing the results with health authorities around the world.”
FAILED TRIAL: Ph II trial of poziotinib fails to meet pre-specified primary endpoint in Cohort 1 in 2L+ EGFR exon 20 insertion mutations positive NSCLC patients
Joe Turgeon, President and CEO of Spectrum Pharmaceuticals said, “While the response rate of Cohort 1 in this trial was lower than we expected, the positive signals observed for this cohort provide support for the continued clinical evaluation of poziotinib in this patient population with significant unmet medical need. We look forward to providing read outs from Cohorts 2 and 3 in 2020, and plan to provide an update on the overall program strategy during the first quarter of 2020 after a full evaluation of the data from Cohort 1 is completed.”
FAILED TRIAL: Ph III ASPEN trial of Zanubrutinib compared to Ibrutinib fails to meet primary endpoint in Waldenström’s Macroglobulinemia patients
“Our researchers sought to design a BTK inhibitor that would improve efficacy and decrease side effects in patients by maximizing BTK inhibition and minimizing off-target binding. We took a bold approach to our clinical development plan by evaluating zanubrutinib directly against ibrutinib in patients with WM and are encouraged by the improvements in VGPR rates and safety,” said Jane Huang, M.D., Chief Medical Officer, Hematology at BeiGene. “The ASPEN trial, which was the largest prospective trial for patients with WM ever run, showed consistent safety advantages for patients treated with zanubrutinib compared to ibrutinib. While falling short of a statistically significant improvement in CR and VGPR, we believe the trial demonstrated that zanubrutinib is a highly potent BTK inhibitor that has clinical benefit and trends toward increased response quality.”
Click Here for more Trial Results
Trial Status/Progress
Ph III LIBRETTO-431 clinical trial [NCT04194944] for selpercatinib (LOXO-292) initiated in RET fusion-positive NSCLC patients
"Given the remarkable results of the LIBRETTO-001 trial, I am excited to open this important Phase 3 trial of selpercatinib, a highly selective and potent molecule that has previously demonstrated sustained responses with a well-tolerated safety profile," said Professor Ben Solomon, principal investigator at the Peter MacCallum Cancer Centre in Melbourne Australia. "This trial endeavors to generate outcome data that place patients with RET fusions alongside those with EGFR mutations and ALK fusions, as driver-positive populations that should be treated with targeted therapies in the first-line setting, rather than chemoimmunotherapy."
Enrollment completed in pivotal Ph III trial of SGX301 in the treatment of Cutaneous T-cell Lymphoma
"We are pleased to have completed enrollment and look forward to the top-line results in the first quarter of next year, particularly in light of the DMC recommendation at the interim analysis which observed a beneficial drug effect," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix.  "We have invested a significant amount of the Company's resources into the CTCL development program and continue to positively position this fast-tracked program for approval.  We believe SGX301 has the potential to be a valuable therapy in the front-line treatment of early stage CTCL, which is an orphan disease and area of unmet medical need."
Click Here for more Trial Progress/Status
Conference Coverage
61st American Society of Hematology (ASH) Annual Meeting, 2019
  1. AbbVie presented long-term data from a post-hoc analysis from the Ph III MURANO trial further supporting the sustained clinical benefit of fixed duration treatment with VENCLEXTA®/VENCLYXTO® (venetoclax) + rituximab (VenR) in R/R CLL patients
  2. Roche presents updated analysis of Ph III CLL14 trial to demonstrate the continued clinical benefit of fixed-duration, chemotherapy-free Venclexta/Venclyxto-based treatments in 1L CLL patients
  3. AbbVie presented improved PFS from more than 7-year analysis from three clinical trials (Ph II SPARK, Ph III RAY and Ph II PCYC-1104) of early treatment with IMBRUVICA® (ibrutinib) monotherapy in 2L+ MCL patients
  4. AbbVie showed extended follow-up Ph III E1912 trial data underscored sustained efficacy and safety of IMBRUVICA® (ibrutinib) in 1L CLL patients
  5. IMBRUVICA® (ibrutinib) + VENCLEXTA®/VENCLYXTO® (venetoclax) combination data showed high rates of disease clearance in 1L CLL patients from the Ph II CAPTIVATE (PCYC-1142) trial
  6. Autolus Therapeutics announces new data showcasing clinical progress of AUTO3 in B cell malignancies
  7. TG Therapeutics announces oral presentation of Umbralisib, Ublituximab and Venetoclax triple combination Ph I/II data in R/R CLL patients
  8. Karyopharm presents XPOVIO® (Selinexor) and Eltanexor data including updates from Ph Ib/II STOMP trial, STORM trial, and MAMMOTH trial
  9. Data from investigator-sponsored Ph II study of Calithera’s Telaglenastat with Azacitidine in MDS patients to be presented
  10. Stemline Therapeutics highlights three ELZONRIS presentations, including an oral presentation in Myelofibrosis
  11. Sunesis Pharmaceuticals announces data from ongoing Ph Ib/II trial of Vecabrutinib in CL and other B-cell malignancies patients
  12. Data on Rafael Pharmaceuticals’ CPI-613® (devimistat) in patients with relapsed Burkitt Lymphoma presented
  13. Regeneron Pharmaceuticals announced initial clinical data for BCMAxCD3 bispecific antibody REGN5458 in RRMM patients
  14. Eli Lilly announced interim clinical data from Ph I/II BRUIN dose escalation trial of LOXO-305
  15. BeiGene announces clinical data on BRUKINSA™ (Zanubrutinib) from two trials in CLL/SLL patients
  16. Oncopeptides presents promising data from the Ph II ANCHOR combination study in RRMM patients
  17. Kura Oncology reports clinical and regulatory updates for Tipifarnib in Angioimmunoblastic T-Cell Lymphoma
  18. Kite presents positive results from pivotal ZUMA-2 trial in R/R MCL patients
  19. Bristol-Myers Squibb announced data from multiple studies evaluating CD19-directed CAR-T theraypy lisocabtagene maraleucel (liso-cel) with a defined composition of purified CD8+ and CD4+ CAR T cells
  20. ArQule announces final Ph I clinical data for reversible BTK inhibitor, ARQ 531
  21. Agios presented translational data to further characterize the role of TIBSOVO® (ivosidenib) treatment in IDH1 mutant AML patients
  22. Efficacy, durability of response and safety of Onvansertib demonstrated in completed Ph Ib trial in AML patients
  23. ImmunoGen presented updated findings from Ph I study of IMGN632
  24. Forty Seven, Inc. announces updated data from Magrolimab trial showing robust, durable activity in MDS/AML patients
  25. BerGenBio ASA provided an update from the Ph II bemcentinib (BGB324) study in combination with low-dose cytarabine (LDAC) in elderly AML patients
  26. ADC Therapeutics SA announced interim efficacy and safety data from Ph II trial of ADCT-402 (loncastuximab tesirine) in R/R DLBCL patients
  27. Constellation Pharmaceuticals provided updated preliminary data from MANIFEST trial with CPI-0610
  28. Atara Biotherapeutics, Inc. presented long-term clinical results from a multicenter Expanded Access Protocol (EAP) study of tab-cel® (tabelecleucel) for EBV+ PTLD
  29. Novartis Kymriah® demonstrates consistent efficacy and safety outcomes in US patients when used in real-world setting
  30.  Janssen presented initial results for BCMA CAR-T Therapy JNJ-4528 showing early, deep and high responses in RRMM patients
  31. Bristol-Myers Squibb announces Liso-Cel met primary and secondary endpoints in TRANSCEND NHL 001 study
  32. Bristol-Myers Squibb and bluebird bio announce positive top-line results from the pivotal Ph II KarMMa study of Ide-cel in RRMM patients
  33. Genentech announced new data on novel CD20-CD3 bispecific cancer immunotherapies in patients with difficult-to-treat lymphomas
  34. Kite announces long-term data From ZUMA-1 showing approximately half of refractory Large B-cell Lymphoma patients were alive three years after Yescarta treatment
  35. Takeda presented results from the Ph III TOURMALINE-AL1 trial of NINLARO in patients with amyloidosis
MedNess Plus
FDA approves Ervebo vaccine for the prevention of Ebola virus disease
“Today’s approval is an important step in our continuing efforts to fight Ebola in close coordination with our partners across the U.S. Department of Health and Human Services, as well as our international partners, such as the World Health Organization. These efforts, including today’s landmark approval, reflect the FDA’s unwavering dedication to leveraging our expertise to facilitate the development and availability of safe and effective medical products to address urgent public health needs and fight infectious diseases, as part of our vital public health mission.”
FDA approves Ubrelvy tablets for the treatment of migraine in adults
“Migraine is an often-disabling condition that affects an estimated 37 million people in the U.S.,” said Billy Dunn, M.D., acting director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research. “Ubrelvy represents an important new option for the acute treatment of migraine in adults, as it is the first drug in its class approved for this indication. The FDA is pleased to approve a novel treatment for patients suffering from migraine and will continue to work with stakeholders to promote the development of new safe and effective migraine therapies.”
FDA grants priority review designation to risdiplam for the treatment of spinal muscular atrophy (SMA)
“The FIREFISH and SUNFISH trials were designed to represent the real-world spectrum of people living with SMA and include many people previously underrepresented in clinical trials,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We look forward to working closely with the FDA to explore broad access to risdiplam for all individuals in the community who might benefit.”
FDA approves Oxbryta for the treatment of sickle cell disease in adults and patients twelve years and older
“Today’s approval provides additional hope to the 100,000 people in the U.S., and the more than 20 million globally, who live with this debilitating blood disorder,” said Acting FDA Commissioner Adm. Brett P. Giroir, M.D. “Our scientific investments have brought us to a point where we have many more tools available in the battle against sickle cell disease, which presents daily challenges for those living with it. We remain committed to raising the profile of this disease as a public health priority and to approving new therapies that are proven to be safe and effective. Together with improved provider education, patient empowerment, and improved care delivery systems, these newly approved drugs have the potential to immediately impact people living with SCD.”
Click Here for more MedNess Plus
MedNess Business
Onco-Updates
WHATS HAUNTING THE KRAS INHIBITORS? 

It looks like KRAS will dominate most of 2020 too. The FIrst week of 2020 saw Merck investing nearly $2.5 B on Taiho and Astex to access their small molecule library that includes KRAS inhibitors. Amgen. JNJ, BI, Eli Lilly, and Mirati are some of the other players who have drugs in trial. Amgen's clinical data shows a 90% decrease in tumor size in lung cancer patients. Mirati similarly has shown positive data in their Phase II studies. 

However, a recent publication in Nature from Piro Lito's group might be interesting as the field heats of for the players. 
KRAS exists in an active and inactive conformational state. It is the inactive state that gets inhibited by the inhibitors. The group tested the inhibitors in an isogenic cell population and showed that upon adding the inhibitor, some cancer cells are sequestered in a quiescent state with low KRAS activity. Whereas there's a population of cancer cells that chooses to ignore and continues to grow. It appears that this varying response to KRAS inhibition occurs because some quiescent cells produce a new version of KRAS(G12C) in response to MAPK pathway that is inhibited. This new form of KRAS(G12C) is maintained in its active, and thus drug-insensitive state by EGFR and ARK signaling. The group cautions about the "adaptive fitness" mechanism of the cancer cells that allows a particular population of cancer cells to escape the drug. Suppressing this variable pathway is a must for a sustained and complete remission of cancer. 
Collated by : Ananda Ghosh
Bio-Pharma and MedTech
GOOD NEWS OR BAD NEWS FOR AAV BASED GENE THERAPY?
As we celebrate the era of gene therapy, a recent report from Denise Sabatino's group of the Children's Hospital of Philadelphia reported at the ASH meeting seems to bring both positive and negative news.

In a study that used AAV based gene therapy to treat dogs with Haemophilia A, supplementing the missing factor VIII, the transgene, or more often, the fragments of the regulatory sequences were found to be integrated into the genome of the liver cells. Often, the integration happened near growth activating genes, thereby raising a concern that the AAV based therapy can increase the risk of cancer unexpectedly.

The good news is, the integration can result in stable expression of the gene that gets supplemented.

The FDA approved the first AAV based therapy for retinal dystrophy in 2017, followed by Zolgensma for SMA in 2019. In 2020 a treatment for Haemophilia A is expected to get approved by the FDA. Read the full article here
Collated by : Ananda Ghosh
Click Here for more MedNess Business
Editors' Desk
Richa Tewari, PhD
Oncology News
Esha Sehanobish, PhD
MedNess Plus
Mayur Vadhvani, PhD
Business News
Abhi Dey
Consulting Editor
Arundithi Ananthanarayanan
I-cube
Nisha Peter, PhD
Managing Editor
Ananda Ghosh, PhD
Founder
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The editors take care to share authentic information.  In case of any discrepancies please write to medness.newsletter@gmail.com
The sponsors do not have any influence on the nature or kind of the news/analysis reported in MedNess. The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of Medness. Examples of analysis performed within this article are only examples. They should not be utilized in real-world analytic products as they are based only on very limited and dated open source information. Assumptions made within the analysis are not reflective of the position of anyone volunteering or working for Medness. This blog is strictly for news and information. It does not provide medical advice, diagnosis or treatment nor investment suggestions. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
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