본문바로가기

KDDF -재단법인 범부처신약개발사업단

media
범부처신약개발사업단에 대한 뉴스 및
다양한 사업단소식을 알려드립니다

신약개발연구동향

홈 > 미디어룸 > 신약개발연구동향
[전문가기고_조제영] Review of FDA CDER Approved Drugs in 2019(2)
2020년 03월 30일
첨부파일

Review of FDA CDER Approved Drugs in 2019

 

(본 내용은 FDA에서 발간한 New Drug Therapy Approvals in CDER, 2019의 내용 및 FDA 허가 검토자료를 바탕으로 작성되었다.)

본 리뷰에서는 2019 FDA CDER Approved Drugs 중 First-In-Class로 허가 받은 약물을 요약하겠으며, 번역에 따른 제품의 그릇된 이해 방지를 위하여 영문 그대로 발췌, 요약하였다.

 

2019년 Fist-In-Class 로 FDA의 허가를 받은 약물은 Adakveo, Balversa, Cablivi, Evenity, Givlaari, Ibsrela, Nourianz, Oxybryta, Padcev, Polivy, Petomanid, Reblozyl, Reyvow, Scenesse, Turalia, Vyleesi, Vyndaqel, Vakix, Xpovio와 Zulresso가 있다. 이 중 일부의 약물에 대한 치료 적응증과 Pharmacoligical Class에 관하여 Table 형식으로 요약하였으며, FDA 허가를 위한 의약품의 개발 시, 개발 제품이 동 적응증에 있어 기 표준 치료제의 Unmet Medical Needs를 만족해 줄 수 있는지, 유효성 및 안전성 등의 improvement를 꾸준히 확보하고 Benefit 대비 Risk를 꾸준히 검증해 나가는 단계가 제품의 허가 유무를 판단하는 기준임을 재 인식하는데 도움이 되었으면 한다.

 

Summary of 2019 FDA CDER Approved Drugs as First-In-Class

Drug

Name

Indication(s)

Pharmacologic Class/Unmet Medical Needs

 

Adakveo

(Crizanlizumab-tmca)

Adakveo is indicated to reduce the frequency of vasoocclusive crises (VOCs) in adults and pediatric patients aged 16 years and older with sickle cell disease.

 

Sickle cell disease (SCD) is an inherited blood disorder caused by a mutation in the ß-globin gene which progresses into a complex disease characterized by acute and chronic inflammation.

 

Adakveo is a humanized IgG2 kappa monoclonal antibody that binds to P-selectin and blocks interactions with its ligands including P-selectin glycoprotein ligand 1.  Binding P-selectin on the surface of the activated endothelium and platelets blocks interactions between endothelial cells, platelets, red blood cells, and leukocytes.

 

There are limited treatment options and a high unmet medical need. VOCs are typically managed symptomatically with analgesics and other supportive therapies. The FDA-approved therapies to reduce the frequency of OVCs in patients with SCD are hydroxyurea/hydroxycarbamide (HU/HC) Droxia;Bristol Myers Squibb) and L-Glutamine (Endari;Emmaus Medical, Inc.). The use of these agents is complicated by the side effects leading to intolerance or unwillingness to use these therapies, and many patients are unwilling to accept the risks of these pre-approved treatment. Thus a significant unmet medical needs exist for new drugs for the treatment of SCD VOCs.  

Adakveo’s SUSTAIN trial showed a clinically meaningful and statistically significant decrease in annual rates of VOCs compared to placebo. 

Balversa

(Erdafitinib)

Adult patients with locally advanced or metastatic urothelial carcinoma (UC), that has:

-susceptible FGFR2 or FGFR2 genetic alterations

-progressed during or following at least one line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

 

Select patients for therapy based on an FDA-approved companion diagnostic for BALVERSA

Balversa inhibit FGFR phosphorylation and signaling and decrease cell viability in cells expressing FGFR genetic alterations.

 

Patients with locally advanced or metastatic urothelial cancer have a poor prognosis despite the high response rate seen with standard platinum/gemcitabine chemotherapy.

While pembrolizumab has received regular approval in the second-line setting, patients whose tumors harbor FGFR alterations represent a molecularly-defined subset of patients with urothelial carcinoma.

This subset may have a lower response rate to PD-L1/PD-1 inhibitors and represents a population of patients for which an unmet medical need exists.

 

Balversa has demonstrated a good response rate with a median duration of response of approximately half a year and an acceptable safety profile from their BLC2001 trial that enrolled patients with locally advanced or metastatic urothelial cancer who had tumors with FGFR3 point mutations (R248C, S249C, G370C, Y373C) or FGFR fusion (FGFR2-CICC1, FGFR2-CASP7, FGFR3-TACC3, FGFR3-BAIAP2L1). The risk-benefit profile of Balversa is acceptable in the approved patient population. Clinical trial BLC3001 is ongoing and will provide further data on the efficacy and safety of Balversa in locally advanced or metastatic urothelial cancer.

Cablivi (Caplacizumab-yhdp)

Cablivi is indicated for the treatment of adult patients with acquired Thrombotic Thrombocytopenic Purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy.

 

aTPP is a rare blood disorder characterized by clotting in small blood vessels (thromboses), resulting in a low platelet count. This results in a low platelet count, low red bold cells due to their breakdown, and often kidneys, heart, and brain dysfuction. A lack of activity in the ADAMTS13 enzyme (a type of protein in the blood) causes TPP.

Cablivi is a humanized bivalent anti-von Willebrand Factos (vWF) antibody fragment that consists of two identical building blocks, genetically linked by a three alanine linker. Caplacizumab blocks the A-domain of vWF and inhibits the interaction vWF and platelets, therby reducing vWF mediated platelet adhesion.

 

Current treatment for aTPP includes daily plasma exchange. A high proportion of patients (15-20%) have an exacerbation of the disease when plasma exchange is stopped. Additional therapy includes corticosteroid, rituximab (off-label), and/or other immunosuppressive drugs such as cyclophosphamide, vincristine, or cyclosporine.

 

The benefit of Cablivi when added to daily plasma exchange and corticosteroid therapy was demonstrated in HERCULES trial. Overall, the proportion of patients with aTTP-related death, recurrence of a TTP or at least one treatment-emergent major thromboembolic event was significantly lower among in the Cablivi treatment arm compared to the placebo treatment arm. However, generally, bleeding adverse events were reported more frequently among patients treated with Cablivi compared to patients treated with placebo due to the MOA of the drug. Risk-benefit analysis favors approval.

Evenity (Romosozumab)

EVENITY is indicated for the treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy.

EVENITY is an IgG humanized monoclonal antibody that binds and inhibits the action of sclerostin, a regulatory factor in bone metabolism.

Sclerostin is thought to act by binding to low-density lipoprotein receptor-related proteins 4,5, and 8 (LRP4, LRP5, and LRP6), inhibiting Wingless-related integration (Wnt) signaling and reducing osteoblast-mediated bone formation. EVENITY increases bone formation and decreases bone resorption.

EVENITY increases the bone formation marker procollagen type 1 N-telopeptide (P1NP) with a peak increase from baseline of approximately 145% compared to placebo 2 weeks after initiating treatment.

Multiple therapies (Bisphosphate, RANK ligand inhibitors, Estrogen agonist/antagonists, Calcitonin, Denosumab, Teriparatide and Raloxifene) are available for the treatment of osteoporosis in postmenopausal women. Rare but serious side effects have decreased the usage of some of the currently available therapies and many patients with osteoporosis who would benefit from therapy remain untreated. Additional therapies in a new class. Evenity, will expand the treatment option.

Givlaari (Givosiran)

Givlaari is indicated for the treatment of adults with acute hepatic porphysia (AHP).

 

AHP is a rare disease that is the result of increased levels of toxic heme intermediate molecules (ALA and Porphobilinogen (PBG)) in the body. These heme intermediates results in acute painful attacks and increase the risk of neurovisceral damage systemically.

Givlaari is an Aminolevulinic Acid (ALA) synthase 1-directed small interfering RNA.

 

Hemin (approved in 1983) is the only approved drug available for treatment of AHP and has an indication that is limited to female patients with acute intermittent porphyria attacks related to the menstrual cycle after initial carbohydrate therapy is known or suspected to be inadequate.

ENVISION clinical study for 6month double blind study showed that 2 attacks per patient in the Givlaari compared to 14 attacks per patients in the placebo arm. In safety evaluations, treatment with Givlaari appears to be tolerable.

The benefit-risk analysis favors approval of Givlaari for the treatment of adult patients with AHP.

Ibsrela (Tenapanor)

Ibsrela is indicated for treatment of irritable bowel syndrome with constipation (IBS-C) in adults.

Ibsrela is small molecule which inhibit the sodium-hydrogen exchanger 3 (NHE3). NH3 is also known as SLC9A3 and Na+/H+ exchanger. It regulates sodium and water absorption and pH by exchanging extracellular sodium for intracellular hydrogen ions. Inhibition of NHE3 results in increased secretion of water into the intestinal lumen and looser bowel movements.

 

IBS-C affects a large population and there is a significant unmet medical need for the patients. There are currently four drugs approved in the United States for the treatment of IBS-C. Lubiprostone (Amitiza) activates type-2 chloride channels in gastrointestinal tract epithelial cells to increase secretion of fluid in the intestine but is limited to use in women. Two of the other approved treatments for IBS-C are guanylate cyclase-C agonists, including linaclotide (Linzess) and Plecanatide (Trulance). Additionally, tegaserod (Zelnorm), a serotonin receptor 4 (5-HT4) agnists was withdrawn from the market secondary to cardiovascular risks, was re-introduced to the market with a revised indication restrickted to women less than 65 years of age. All the available alternative therapies demonstrate a modest treatment effects, so there remains a need for additional therapeutic options for patients with IBS-C.

Ibsrela was demonstrated to be effective for the treatment of adults with IBS-C in two adequate and well controlled trials (Study 301 and Study 302). Ibsrela achieved at least a 30% reduction from baseline in average of the worst daily abdominal pain score. The safety profile of Ibsrela supports approval.

 

다음 호에서는 나머지 FIC 제품에 대하여 같은 형식으로 요약하고자 한다.

목록으로
열람하신 정보에 대해 만족하십니까?
평점주기
확인

이메일무단수집거부 개인정보 취급방침 서울시 마포구 마포대로 137 KPX빌딩 9층 대표전화 02-6379-3050

© Korea Drug Development Fund. All Rights Reserved.