Insights+: Breakthrough Therapy Designation by the US FDA in 2018

 Insights+: Breakthrough Therapy Designation by the US FDA in 2018

Breakthrough Therapy Designation by the US FDA in 2018

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 drugs 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. In 2018, the FDA granted eight Breakthrough Therapy Designations including two from Novartis’ portfolio i.e, Kisqali & Promacta for breast cancer & aplastic anemia respectively in addition to INDs including SAGE-217 & PTI-428 . Our team at PharmaShots has compiled a list of eight Breakthrough Therapies granted by the US FDA.

1. Novartis’ Kisqali + Aromatase Inhibitor Received FDA’s Breakthrough Therapy Designation for HR+/HER2- Advanced Breast Cancer

Date – January 03, 2018

Product – Kisqali, Ribociclib, Tamoxifen, Goserelin

The BT designation was based on P-III MONALEESA-7 study results assessing Kisqali + tamoxifen/aromatase inhibitor + goserelin vs tamoxifen/aromatase inhibitor + goserelin in 672 pre/perimenopausal women with HR+/HER2- advanced breast cancer. The P-III MONALEESA-7 study resulted in m-PFS (22.1, 27.5 vs 11.0, 13.8 mos.), AEs- neutropenia (60.6% vs. 3.6%), leukopenia (14.3% vs. 1.2%), no new safety signals observed. Kisqali (ribociclib) is a CDK4/6 (cyclin-dependent kinase) inhibitor, approved in the US for postmenopausal women with HR+/HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor and has received its first BT designation based on P-III MONALEESA-2 study in Aug’16.

2. Novartis’ Promacta Received FDA’s Breakthrough Therapy Designation for Severe Aplastic Anemia (SAA)

Date – January 04, 2018

Product – Promacta, Eltrombopag

The BT designation to Promacta (eltrombopag) + standard immunosuppressive therapy (IST) for patients with 1L severe aplastic anemia (SAA). The BT designation was based on research conducted at NIH demonstrated complete response @6mos. (52%) & ORR (85%). Promacta (eltrombopag) is a TPO receptor agonist and has received FDA’s & EU’s approval for thrombocytopenia in pediatric patients >1yr with insufficient response to corticosteroids and immunoglobulins.

3. Sage Therapeutics’ SAGE-217 Received FDA’s Breakthrough Therapy Designation for CNS Disorders

Date – February 07, 2018

Product – SAGE-217

The BT Designation was based on P-II study results assessing SAGE-217 vs PBO in 89 patients with moderate to severe major depressive disorder (MDD). The P-II study resulted in meeting 1EPs, reduction in the Hamilton Rating Scale for Depression (HAM-D), safe, effective & well tolerated. SAGE-217 (qd, PO) is an allosteric modulator targeting synaptic & extrasynaptic GABA receptors used for regulating CNS function and is currently developed for MDD, Parkinson’s disease and sleep disorders.

4. Proteostasis’ PTI-428 Received FDA’s Breakthrough Therapy Designation for Cystic Fibrosis (CF)

Date – March 12, 2018

Product – PTI-428, Orkambi, PTI-808, PTI-801

The BT designation was based on P-II study results assessing PTI-428 (50 mg, qd) vs PBO in 24 CF with F508del mutation on background treatment with Orkambi for 28 days. The P-II study resulted in the improvement of forced expiratory volume in 1 second (ppFEV1) 5.2%; an increase in nasal mucosal CFTR protein. Proteostasis’ PTI-428 is a part of triple combination therapy including PTI-808 (potentiator) & PTI-801 (corrector) involved in increasing the level of CFTR protein to treat CF patients who are homozygous for the F508del mutation in the CFTR gene.

5. Roche’s Hemlibra Received FDA’s Breakthrough Therapy Designation for Hemophilia A without Factor VIII Inhibitors

Date – April 17, 2018

Product – Hemlibra, Emicizumab

The BT designation was based on P-III HAVEN 3 study results assessing Hemlibra vs no prophylaxis in 152 patients in the ratio (2:2:1) with hemophilia A + prior treated with factor VIII therapy aged >12years. The P-III HAVEN 3 study resulted in a reduction in treated bleeds, superior to prior factor VIII prophylaxis, no thrombotic microangiopathy, no new safety signals observed. Hemlibra (emicizumab) IV is a bispecific factor IXa- and factor X-directed Ab, with recommended dose qw, q2w, developed by Chugai and co-developed by Roche and Genentech. In 2017, Hemlibra received FDA’s approval to treat hemophilia A with factor VIII inhibitors in adults and children.

6. Genentech’s Xolair Received FDA’s Breakthrough Therapy Designation for Food Allergies

Date – August 13, 2018

Product – Xolair, Omalizumab

The BT designation was granted based on seven clinical studies evaluating safety and efficacy for allergens including peanut, milk, egg, and others. The BT designation for Xolair (omalizumab) was to prevent severe allergic reactions following accidental exposure to one or more foods in people with allergies. Genentech and Novartis have worked with NIAID and the Consortium of Food Allergy Research (CoFAR) initiating a pivotal study for evaluating the efficacy and safety of Xolair in multiple food allergies. Additionally, Genentech and Novartis are working to co-develop and co-promote Xolair.

7. Compass Pathways’ Psilocybin Therapy Received FDA’s Breakthrough Therapy Designation for Treatment-Resistant Depression

Date – October 23, 2018

Product – Psilocybin

The BT designation followed a clinical study assessing Psilocybin in 19 patients with treatment-resistant depression, conducted at Imperial College London in 2015. FDA’s BT designation is granted to the drugs that have shown substantial improvement over currently available therapies in serious or life-threatening conditions on at least one clinically significant endpoint with benefits of Priority Review and accelerated approval. Psilocybin is a serotonin 2 receptor agonist, being evaluated in a clinical study for treatment-resistant depression in EU and North America.

8. Seattle Genetics’ Adcetris (brentuximab vedotin) Received FDA’s Breakthrough Therapy Designation for Frontline Peripheral T-Cell Lymphomas

Date – November 15, 2018

Product – Adcetris, Brentuximab Vedotin, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone

The BT designation was based on P-III ECHELON-2 study results assessing Adcetris + CHP vs CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in 450 patients with CD30-expressing peripheral T-cell lymphoma across North America, EU, and Asia. The P-III ECHELON-2 study resulted in meeting its 1EPs & 2EPs, improvement in PFS, superior OS, CRR and ORR were statistically significant in favor of the Adcetris + CHP arm, safe & effective data. Adcetris (brentuximab vedotin, IV) is an ADC with anti-CD30 mAb, co-developed by Seattle Genetics and Takeda and has received FDA’s approval for 5 indications including r/r CD30+ Hodgkin lymphoma following ASCT, r/r sALCL, CD30+ CTCL.

Shiwani Sharma

Shiwani Sharma is a Senior Editor at PharmaShots. She has in-depth knowledge of lifesciences industry including pharma and biotech sectors. She also covers news in field of Digital Health, Medtech and regulatory approvals from the US FDA, EU, and other global regulatory bodies in the industry. Additionally, she also writes Whitepapers, analysis reports, blogs on pharma and biotech industry. She is graduate in Biotechnology. She can be contacted on

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