Name of firm/applicant

Transcription

1 Recommendation:- The 18 th Subject Expert Committee (Oncology & Hematology) deliberated the proposals on and recommended the following:- Agenda no. Drug name Name of firm/applicant Recommendations 1. Decitabine(psc) M/s. J &J The firm presented the safety data on Decitabine in Indian subjects vis-à-vis the global data and summarized that safety of Decitabine used in Indian patients is The committee noted that the drug was launched in India for marketing in November 2010 and so far around 290 subjects have been exposed to the drug in the country. The standard of care is supportive and the drug Decitabine is an innovative agent and the committee opined that there is an unmet need of this drug in the country. At present, another new drug Azacitidine which is of the same class is also being granted marketing authorization in India recently. The risk Vs benefit ratio appears favorable. 2. Trabectedine (PSC) M/s. J &J The firm presented the safety data on Trabectidine in Indian subjects vis-à-vis the global data and summarized that safety of Trabectidine used in Indian patients is The committee noted that the drug was launched in India for marketing in 2011 and so far around 427 subjects have been exposed to The drug Trabectidine is an innovative agent for a subset of sarcoma patients and no other comparable drug is available in the country at present. The Committee opined that there is an unmet need of this drug in the country and no safety signals specifically for the Indian population have been identified. The risk Vs benefit ratio appears favorable. 3. Pemetrexete (PSC) M/s. Eli Lilly The firm presented the safety data on Pemetrexate in Indian subjects vis-à-vis

2 the global data and summarized that safety of Pemetrexate used in Indian patients is The committee noted that the drug Pemetrexate is an innovative agent and is now used as standard of care. Since launching of Pemetrexate in the year 2006, so far around 3500 subjects have been exposed to the drug in the country with no evidence of increased risk. This drug fulfills the unmet need in the India. The risk Vs benefit ratio appears favorable. 4. Bendamustine(PSC) M/s. NATCO The firm presented the safety data on Bendamustine in Indian subjects vis-à-vis the global data and summarized that safety of Bendamustine used in Indian patients is The committee noted that the drug was launched in India for marketing in the year Further, the committee opined that the drug Bendamustine is an innovative agent and is now being widely used in Indian population. Also, the safety data is comparable with global data not generating any safety signal. There are more reports of rash and pruritus in Indian population but fewer reports of myelosuppression and other infections. The risk Vs benefit ratio appears favorable. 5. Nexavar M/s. Bayer The committee noted that the firm has proposed to conduct a phase IV observational study with Nexavar to evaluate its safety and efficacy in Indian subjects. Although the inclusion criteria mentions that the patients on Nexavar will be recruited it is not clear how inducement by the Investigator will be avoided as the patient will be paying for the drug and this would be only observational study. did not recommend the proposed study in the present form. 6. Bendamustine HCL for M/s Natco The firm presented rationale for

3 injection 25mg/vial requirement of lower strength Bendamustine HCL for injection 25mg/vial and stated that the dose for Chronic lymphocytic leukemia (CLL) is 100 mg/m 2. Based on their body surface area, patients usually require 140 to 175 mg of drug hence, they need to buy 2 vials of 100mg The committee noted that there is rationale for a lower concentration as it will reduces wastage of the medicine which would make it economically viable. The indication for the lower strength Bendamustine HCL for injection 25mg/vial is same i.e for the treatment of Chronic lymphocytic leukemia (CLL), after deliberation the committee recommended for the approval of Bendamustine HCL for injection 25mg/vial (lower strength) for the already approved indication. 7. Sorafenib M/s Bayer The committee noted that the drug is marketed in India since 2007 for the treatment of patients with advanced renal cell carcinoma and since 2008 for the treatment of hepatocellular Carcinoma. Approximate 1700 patients have been exposed. Two more generic drugs are also approved. No safety signals have been generated so far. This drug is approved in 49 countries for Treatment of patients with locally advanced or metastatic differentiated thyroid carcinoma refractory to radioactive iodine including USA, UK, Europe etc. USFDA and EMA granted the Orphan drug status for this drug. It also shows the favorable risk benefit ratio. After deliberation the committee recommended for the approval additional indication i.e for Treatment of patients with locally advanced or metastatic differentiated thyroid carcinoma refractory to radioactive iodine. 8. Paclitaxel M/s Intas Firm did not present the revised protocol as recommended by NDAC on However they presented statistical analysis by statistician. This post hoc statistical analysis indicated that the sample size of the phase II study was adequate to give a power of 90%; non-inferiority limit of 10%; and an alfa error of 5%.

4 NDAC reviewed this data and in view of the fact that the test formulation i.e Nanosomal Paclitaxel lipid suspension for Injection 30mg/vial gives about 40 % less bioavailability than that with reference formulation (Taxol) which is statistically significant difference, it is crucial to get statistical effect in the clinical study (ORR). Since the statistical analysis is post-hoc and also excluded one of the arms in the study, the NDAC recommended that this report therefore should be independently evaluated from independent statistician from AIIMS. 9. BIBW2992(Afatinib) M/s Boehringer The risk vs. benefit profile of the test drug I, II and III clinical trials with afatinib alone or in combination with other drugs justify the conduct of this study.the purpose of the study is to investigate the efficacy and safety of Afatinib alone and in combination with weekly paclitaxel or vinorelbine upon progression on afatinib monotherapy. The firm presented Protocol amendment version 7 to stop inclusion of patients into the treatment armb/partb(combination of afatinib+ vinorelbine).dmc recommended treatment in Exp arm (afatinib 40mg+ vinorelbine25 mg weekly i.v.) should be discontinued. After detailed deliberation the committee recommended the protocol amendments.the committee opined that the subjects who are on-going in the study and clinically benefiting, should be continued in the trial. 10. Axitinib M/s Pfizer The risk vs benefit profile of the test drug I and II clinical trials justify the conduct of this study.the purpose of the study is to compare the progression free survival (PFS) of treatment naïve patients with mrcc receiving Axitinib vs Sorafenib. The firm presented the protocol amendment to update the new safety guidelines and the schedule of activities vis-a vis tests and procedures. The committee after deliberation recommended the protocol amendments.

5 11. Dasatinib M/s BMS The risk vs. benefit profile of the test drug I clinical trials justify the conduct of this study.the purpose of the study is to assess dasatinib therapy in children and adolescents with newly diagnosed chronic Phase CML or with Ph+ Leukaemias Resistant or Intolerant to Imatinib. The firm presented the Protocol amendment versions 13, 15 and 17 to include a subcohort of subjects 0-18yrs of age who will receive PFOS, permanent closure for enrollment to cohort 02 and criteria for WOCBP. The committee after deliberation recommended all the three protocol amendments. 12. LDK378 M/s Novartis The risk vs benefit profile of the test drug from preclinical studies including single dose, repeat dose toxicity and phase I clinical trial etc, justify the conduct of this study.the purpose of the study is to evaluate safety of the test drug (LDK378) when used in patients with ALK positive locally advanced or metastatic NSCLC. ALK-targeted therapy with LDK378 may provide improved anti-cancer activity over standard first-line chemotherapy in treatment-naive patients with ALKrearranged non-squamous NSCLC. 13. Octafibrin M/s Max Neeman The committee reviewed the proposed phase III study protocol and recommended the conduct the study. The risk vs benefit profile of the test drug from preclinical single dose toxicity, reproductive toxicity study justify the conduct of this study.purpose of the study is to assess the efficacy and safety of IMP (octafibrin) in subjects with Congenital Fibrinogen Deficiency.Currently available treatments include large volumes of plasma or cryoprecipitate for serious and emergency bleeds as well as in the management of surgical cases. Fibrinogen concentrates availability may help in decreasing the volumes to be infused in emergency and serious bleeds etc. The committee reviewed the presentation made by the applicant and recommended

6 14. Hercules plus taxone vs. Herceptin plus taxone M/s Inc Research the conduct of the phase III study. The risk vs benefit profile of the test drug from preclinical repeated dose toxicity studies and phase I pharmacokinetics, phase III bioequivalence study justify the conduct of this study.the study drug is a biosimilar of Trastuzumab which is the existing therapeutic option for metastatic her2 positive breast cancer patients. Multi source availability of Trastuzumab may be beneficial to Indian subjects. The committee reviewed the proposed phase III study protocol and recommended the conduct of the study. 15. Trastuzumab emtansine M/s Roche The Risk vs Benefit profile of the test drug I, II and III clinical trials justify the conduct of this study. There is no standard therapy for patients with HER2 Positive mbc who have progressed on both of the approved HER2- Directed therapies (Trastuzumab and Lapatinib). The purpose of the study is to evaluate the efficacy of Trastuzumab emtansine compared with treatment of physician s choice in patients with her2- positive metastatic breast cancer who have received at least two prior regimens of her2-directed therapy. The committee deliberated the proposed protocol amendments (versions B to F)i.e. the inclusion, exclusion criteria, criteria for women of child bearing age etc, and recommends the for the same. 16. Mycobacterium w M/s Cadila Pharmaceutical Ltd. 17. Bevacizumab M/s Reliance Life science Pvt Ltd The firm did not come for presentation. Expert committee reviewed the DSMB report of the Bevacizumab and recommended for the continuation of the study.