Insights+: Breakthrough Therapy Designation by the US FDA in 2019

 Insights+: Breakthrough Therapy Designation by the US FDA in 2019

Breakthrough Therapy (BT) Designation is an expedited review program introduced in Section 902 of the Food and Drug Safety and Innovation Act of 2012. The Breakthrough Designation is granted to the drug candidates as monotherapy or in combination with other drugs intended to treat serious or life-threatening diseases and has shown substantial improvement over available therapies for the disease.  PharmaShots has compiled a list of Breakthrough Therapies granted by the US FDA in 2019.

1. Beigene’s Zanubrutinib (BGB-3111) Received the US FDA’s Breakthrough Therapy Designation for Mantle Cell Lymphoma (MCL)

Date – Jan 16, 2019

Product – Zanubrutinib

  • The BT designation follows the P-II trial assessing Zanubrutinib in patients with 1L mantle cell lymphoma
  • Beigene’s Zanubrutinib is being evaluated globally in seven P-III trials in multiple areas including one for patients with WM with zanubrutinib vs ibrutinib and P-II for r/r follicular lymphoma in combination with Gazyva (obinutuzumab)
  • Zanubrutinib is a BTK inhibitor and has also received NMPA’s (CMPA) priority review for r/r MCL and r/ r CLL/SLL in China

2. Merck’s V114 Received FDA’s Breakthrough Therapy Designation to Prevent Invasive Pneumococcal Disease  

Date – Jan 31, 2019

Product – V114

  • The BT designation is based on P-I/II and P-II results assessing four lots of V114 in healthy adults and infants, demonstrating non-inferiority data on patients
  • FDA’s BT designation is granted to the drugs showing clinical improvement over currently available therapy on at least one clinically significant endpoint with benefits of Priority Review and Accelerated Approval
  • V114 is a 15-valent pneumococcal conjugate vaccine targeted for two disease-causing (22F and 33F), evaluated in P-III for the prevention of IPD in adults

3. AstraZeneca’s MEDI8897 Received FDA’s Breakthrough Therapy Designation and EMA’s PRIME Designation for Lower Respiratory Tract Infection (LRTI) in Infants

 Date – Feb 05, 2019

Product – MEDI8897

  • The FDA’s BT & EMA’s PRIME designation is based on P-IIb trial results assessing MEDI8897 in patients with LTRI caused by RSV in premature infants @150days
  • The P-IIb study resulted in meeting its 1EPs with a reduction in the incidence of medically attended LRTI
  • MEDI8897 is an extended half-life RSV F mAb, used for prevention of LRTI administered as a single dose within 5months and has received FDA’s FT designation in Mar’2015. In Mar’2017, AstraZeneca and Sanofi Pasteur collaborated to jointly commercialize MEDI8897

4. Finch Therapeutics’ CP101 Received FDA’s Breakthrough Therapy Designation for Recurrent Clostridium Difficile (C. difficile) Infection

Date – Feb 11, 2019

Product – CP101

  • The FDA’s BT designation follows P-II PRISM3 study results assessing CP101 vs PBO in patients with recurrent C. difficile
  • FDA’s BT designation is granted to the drugs showing clinical improvement over currently available therapy in serious or life-threatening conditions on at least one clinically significant endpoint with benefits of Priority Review and accelerated approval
  • CP101 is an oral, qd, drug developed using Finch’s Full-Spectrum Microbiota (FSM) platform, targeted for prevention of recurrent C. difficile infections

5. AstraZeneca’s Selumetinib Received the US FDA’s Breakthrough Therapy Designation for Neurofibromatosis Type 1

Date – Apr 01, 2019

Product – Selumetinib

  • The BT Designation follows the P-II SPRINT trial assessing selumetinib as a monothx. (PO) in pediatric patients, aged three years or older with inoperable NF1-related PN
  • The ninth BT designation is granted to the AstraZeneca for the MEK 1/2 inhibitor and the results will further lead to expedited regulatory review
  • Selumetinib is a MEK 1/2 inhibitor, received the US FDA’s ODD to treat NF1 in Feb’2018 and the EMA’s ODD in Aug’2018. In 2017, AstraZeneca and MSD signed a co-development and co-commercialization agreement for selumetinib

6.  Bayer’s Aliqopa (copanlisib) Received the US FDA’s Breakthrough Therapy Designation to Treat Marginal Zone Lymphoma in Adults 

Date – May 29, 2019

Product – Aliqopa

  • The BT designation is based on the P-II CHRONOS-1 study, which involves assessing of 25 patients with r/r MZL who have received at least two prior therapies
  • The study resulted in ORR of overall iNHL population (n=142) was 59.2%, while the MZL patients (23%), @18mos. ORR (60.6% and 78.3%) in FAS population and MZL histology
  • Aliqopa is a PI3K inhibitor with inhibitory activity against PI3K-α and PI3K-δ isoforms expressed in malignant B cells. Additionally, Bayer is conducting two P-III studies CHRONOS-3 and CHRONOS-4 evaluating the safety and efficacy of Aliqopa

7. Merck and Eisai’s Dual Regimen Received the US FDA’s Breakthrough Therapy Designation as 1L Treatment for Advanced Unresectable Hepatocellular Carcinoma

Date – July 23, 2019

Products – Keytruda, Lenvima

  • The BT designation is based on P-Ib KEYNOTE-524/Study 116 trial assessing Keytruda (200mg, IV, q3w) + Lenvima (12mg/day for patients weighing ≥60kg, and 8mg/day for patients weighing <60kg) in patients with unresectable HCC not amenable to locoregional treatment
  • The FDA’s BT designation intended to expedite development and review of medicines for serious or life-threatening conditions
  • This marks the third BT designation for the combination therapy. The first two BT designation for dual regimen was in advanced/m-RCC & advanced/ m-non- MSI-H/ pMMR endometrial carcinoma, received in Jan’2018 & July’2018 respectively

8. Nektar and BMS Received the US FDA’s Breakthrough Designation for Bempegaldesleukin (NKTR-214) + Opdivo (nivolumab) to Treat Advanced Melanoma

Date – Aug 02, 2019

Products Bempegaldesleukin, Opdivo

  • The FDA’s BT designation is based on ongoing P-I/II PIVOT-02 study assessing the doublet therapy in patients with metastatic melanoma. FDA’s BT designation is to expedite the development of medicine targeting life-threatening diseases
  • In Feb 2018, BMS signed a WW development and commercialization agreement with Nektar for its Bempegaldesleukin
  • Bempegaldesleukin is a therapy targeting CD122 receptors, activating CD8+ effector T cells and NK cells and is being evaluated in P-III study in combination with Opdivo Opdivo in patients with 1L advanced melanoma. Opdivo is a PD-1 immune checkpoint inhibitor harnessing the body’s immune system by restoring anti-tumor response

9. AstraZeneca’s Calquence (acalabrutinib) Received the US FDA’s Breakthrough Therapy Designation to Treat Chronic Lymphocytic Leukaemia (CLL) in Adults

Date – Aug 14, 2019

Product – Calquence

  • The FDA’s BT designation is based on the P-III ELEVATE-TN assessing Calquence (100 mg, bid) as monothx. or in combination with obinutuzumab vs chlorambucil + obinutuzumab and in 535 patients in a ratio (1:1:1) in previously untreated patients with CLL and in another P-III ASCEND Trial (ACE-CL-309) involves assessing of Calquence (310 mg) vs rituximab + idelalisib/ bendamustine in 310 patients in a ratio (1:1) with previously untreated patients with CLL
  • The two P-III trials ELEVATE-TN and ASCEND trials resulted in positive data showed increased the time patients lived without disease progression or death, with safety and tolerability that was consistent with its established profile and will serve as the foundation for regulatory submissions later this year
  •  Calquence (acalabrutinib) is a BTK inhibitor and is developed for the treatment of multiple B-cell blood cancers, including CLL, MCL, DLBCL, WM, FL, and MM and other hematologic malignancies

10. Janssen’s Investigational Prophylactic Vaccine Received the US FDA’s Breakthrough Therapy Designation to Prevent Respiratory Syncytial Virus

Date – Sept 04, 2019

Product – Prophylactic Vaccine

  • The US FDA’s breakthrough therapy designation is based on the clinical study assessing the prophylactic vaccine in RSV patients aged ≥60yrs. vs SOC demonstrating substantial improvement in the clinically significant endpoints
  • Following BT designation, Janssen’s vaccine is eligible for all associated FDA features and is currently being evaluated in P-IIb proof of concept study evaluating the safety and efficacy of the vaccine against RSV in adults aged ≥65yrs.
  • The prophylactic RSV senior vaccine comprises the genes encoding for the fusion protein of the RSV virus as an antigen and utilizes Janssen’s adenovector platform (AdVac)

11. Merck KGaA’s Tepotinib Received FDA’s Breakthrough Therapy Designation for Metastatic NSCLC with METex14 Skipping Alterations

Date – Sept 11, 2019

Product – Tepotinib

  • The BT designation is based on an ongoing VISION study (NCT02864992) assessing Tepotinib in 73 patients with m-NSCLC harboring MET exon 14 skipping alterations detected by liquid biopsy (LBx) or tissue biopsy (TBx) across different lines of treatment
  • The VISION study results: ORR and DOR for LBx identified patients assessed by IRC & investigator (50% & 55.30% and 12.4 & 17.1 mos.); ORR and DOR for TBx identified patients (45.1% & 54.9% and 15.7 & 14.3) respectively
  • Tepotinib is an investigational oral MET inhibitor, also being investigated in the INSIGHT 2 study (NCT03940703) in combination with Osimertinib in EGFR mutated, MET amplified, LA/m-NSCLC having acquired resistance to prior EGFR TKI and has received MHLW’s Sakigake designation in Mar’2018

12. Novartis’s Capmatinib (INC280) Received the US FDA’s Breakthrough Therapy Designation for MET-Mutated Advanced Non-Small Cell Lung Cancer

 Date – Sept 16, 2019

Product – Capmatinib

  • The US FDA’s BT designation is based on GEOMETRY mono-1 study involves assessing of Capmatinib and the results were also updated in American Society of Clinical Oncology
  • The BT designation is granted to serious or life-threatening disease therapies demonstrate a substantial improvement over existing therapies on one or more significant preliminary research endpoints
  • Capmatinib is an oral potent and selective MET inhibitor with its expected regulatory submission in Q4’19. In 2009, Novartis signed an exclusive development and commercialization agreement with Incyte for Capmatinib

13. Roche’s Gazyva (obinutuzumab) Received FDA’s Breakthrough Therapy Designation for Lupus Nephritis

Date – Sept 18, 2019

Product – Gazyva

  • The FDA’s BT designation is based on P-II NOBILITY (NCT02550652) study assessing Gazyva in combination with mycophenolate mofetil/mycophenolic acid and corticosteroids vs PBO + MMF/MPO and corticosteroids in 126 patients with ISN/RPS 2003 class III or IV proliferative lupus nephritis
  • The P-II NOBILITY study resulted in meetings its 1EPs & 2EPs i.e, complete renal response (CRR) @52wks. & improvement in overall renal responses and serologic markers of disease activity with no new safety signals respectively
  • Gazyva is mAb targeting CD20, act by attacking target cells, both directly and together with the body’s immune system with its anticipated onset of P-III study in 2020

14.  Achillion’s Danicopan (ACH-4471) Received FDA’s Breakthrough Therapy Designation for Paroxysmal Nocturnal Hemoglobinuria

Date – Sept 25, 2019

Product – Danicopan

  • The FDA’s BT designation is based on safety & efficacy data ongoing P-II study assessing Danicopan in combination with C5 for patients with paroxysmal nocturnal hemoglobinuria (PNH) who are suboptimal responders to C5 inhibitor with its expected results in Q4’19
  •  The US FDA’s BT designation expedite the development and review of drugs for serious or life-threatening conditions
  • The Danicopan is an orally active Factor D inhibitor, act limiting both intravascular and extravascular hemolysis and has received FDA’s ODD in 2017 with its expected onset of P-III study in H1’2020

15.  Janssen’s Niraparib Received the US FDA’s Breakthrough Therapy Designation for Metastatic Castration-Resistant Prostate Cancer

Date – Oct 04, 2019

Product – Niraparib

  • The BT designation is based on P-II GALAHAD study assessing niraparib in adult patients with BRCA1/2 gene-mCRPC and DNA-repair gene defects (DRD) prior treated with androgen-receptor targeting therapies and docetaxel
  • The FDA’s BT designation is granted to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition
  • Niraparib (PO) is a selective PARP inhibitor, currently being evaluated in P-III MAGNITUDE study assessing niraparib + Zytiga (abiraterone acetate) and prednisone in patients with mPC. Additionally, it is being evaluated in P-Ib/II study of niraparib combination therapies for the treatment of mCRPC

16. Usona Institute’s Psilocybin Received the US FDA Breakthrough Therapy Designation for Major Depressive Disorder

Date – Nov 22, 2019

Product – Psilocybin

  • The US FDA has granted the BT designation to psilocybin for promoting the efficient development of programs for psilocybin in MDD
  • The BT designation follows the launch of Usona’s P-II PSIL201 which includes ~80 patients at 7 sites across the US. 2/7 study sites are recruiting while others are expected to be active by Q1’20
  • The BT designation to psilocybin targets the unmet medical need and the potential for improvement over existing therapies and foster Usona’s goal to advance the treatment paradigm toward new drug approval

17. F2G’s Olorofim Received the US FDA’s Breakthrough Therapy Designation to Treat Invasive Mold Infections in Patients with Limited or No Treatment Options

Date – Nov 11, 2019

Product – Olorofim

  • The BT designation follows the P-IIb Trial in patients with IFD or probable invasive aspergillosis (IA) and either refractory disease, resistance, or intolerance to available agents
  • The study resulted in well tolerable results across more than 10 years of patient dosing days with a median therapy duration of 12 wks.
  • Olorofim is first antifungal agent targeted to treat invasive fungal mold infections such as azole-resistant aspergillosis, scedosporiosis, lomentosporiosis, and other rare mold infections and is being developed as IV and oral formulation

18. BMS’ Orencia (abatacept) Received the FDA’s Breakthrough Therapy Designation to Prevent Acute Graft-Versus-Host Disease After Stem Cell Transplant

Date – Dec 04, 2019

Product – Orencia

  • The US FDA BT’s designation is based on P-II study assessing the impact of Orencia on the prevention of severe acute GvHD when added to a standard GvHD prophylactic regimen in patients with hematologic malignancies receiving a stem cell transplant from an unrelated, HLA-matched or mismatched donor
  • A BT designation is granted to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition
  • Orencia is an immunomodulator targeting proteins involved in co-stimulation, thus inhibiting T-cell activation and is an approved therapy to treat multiple RA conditions. If approved by FDA, Orencia will be the first approved therapy to prevent acute GvHD

19. Boehringer Ingelheim’s Ofev (nintedanib) Received the US FDA’s Breakthrough Therapy Designation for Chronic Fibrosing ILDs with a Progressive Phenotype

Date – Dec 04, 2019

Product – Ofev

  • The BT designation is based on P-III INBUILD study results assessing OFEV vs PBO in patients with chronic fibrosing interstitial lung disease (ILDs) with signs of progression for 52 wks. resulted in slowed lung function decline by 57% in the overall population
  • The FDA’ BT designation is established to accelerate the development and review of drugs for serious or life-threatening diseases where preliminary clinical evidence indicate that the therapy may demonstrate substantial improvement over existing therapies
  • Ofev (nintedanib) is a tyrosine kinase inhibitor approved in 70+ countries including the US, EU, and Japan for the treatment of patients living with idiopathic pulmonary fibrosis (IPF) and has also received the US FDA’s BT designation for IPF in July 2014  

20. Chugai’s Nemolizumab Received the US FDA’s Breakthrough Therapy Designation to Treat Pruritus Associated with Prurigo Nodularis

Date – Dec 09, 2019

Product – Nemolizumab

  • Nemolizumab is a novel therapy targeting IL-31 receptor A developed utilizing Chugai’s antibody engineering technology ACT-Ig. The 8th BT designation is granted to the Chugai based on P-II clinical study conducted by Galderma and the results were presented at EADV 2019
  • The BT designation is granted to serious or life-threatening disease therapies demonstrate a substantial improvement over existing therapies on one or more significant preliminary research endpoints
  • Galderma is initiating the P-III trial for nemolizumab in adults with prurigo nodularis in 2020. In 2016, Chugai and Galderma signed a global license agreement for nemolizumab (CIM331), a novel biologic for skin diseases

 21. Agios’ Tibsovo (ivosidenib) Received the US FDA’s Breakthrough Therapy Designation for Patients with Relapsed or Refractory Myelodysplastic Syndrome with an IDH1 Mutation

Date – Dec 16, 2019

Product- Tibsovo

  • The FDA’s BT designation is based on MDS arm of P-I dose-escalation and expansion study assessing Tibsovo (500mg) in 12 patients with r/r MDS with a susceptible IDH1 mutation as detected by an FDA-approved test
  • The P-I study results: median treatment duration (11.4mos.); as of Nov 02, 2018, patients showing response (75%); CR (42%); patients who have CR (60% remained relapse-free @12mos.); 75% were transfusion-independent for 56 days or longer
  • Tibsovo is an IDH1 inhibitor, indicated to treat adults with r/r AML with a susceptible IDH1 mutation as detected by an FDA-approved test

Tuba Khan

Tuba Khan is an Editor and Digital Marketing expert at PharmaShots. She is curious, creative, and passionate about recent updates and innovation in Lifesciences industry. She covers Pharma, Medical devices, Diagnostics and Digital health segment. Tuba also has an experience of digital and social media marketing and can run the campaign independently. She is also certified as a Digital marketer and social media marketer. She can be contacted on tuba@pharmashots.com

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