June 20, 2012
Statement to an FDA Advisory Committee Concerning the Approval of Semuloparin for the Prophylaxis of DVT in Chemotherapy Patients
Good morning. Thank you for the opportunity to testify on behalf of the Cancer Prevention and Treatment Fund. My name is Sonia Nagda. I am a physician, and I received my training in public health at Harvard University. Our organization is dedicated to improving the health of adults and children, and we do that by scrutinizing scientific research. We do not accept contributions from companies that make medical products, so I have no conflicts of interest.
The data that evaluate the use of semuloparin for thromboprophylaxis in chemotherapy patients is based on 1 study of 1,600 patients on the study drug. However, 36% of these patients did not complete three months on the therapy. Of these, 255 patients discontinued treatment due to adverse side effects.
Semuloparin reduced the absolute risk of DVT and fatal and nonfatal pulmonary embolism by 2.2% compared to placebo, but there are serious side effects. There were 19 instances of major bleeding in the semuloparin group, and of these 5 were in a critical location, including pericardial, intracranial, splenic, and intraocular events, compared with no critical bleeds in the placebo group. The drug was tested in patients with colon or rectal, stomach, bladder, ovarian, lung, and pancreatic cancer, but was only found to reduce the risk of thromboembolism in patients with lung and pancreatic cancer. Because there were so few patients with each type of cancer, it would be necessary to include more patients to shed light on the impact that semuloparin has on the development of blood clots.
Many of you have already commented on the questionable heterogeneity of the patient population in the study, and it appears that the sponsor has flung a number of arrows with the hope that one of these would hit the target.
Patients in the study were most commonly on fluoururacil, cisplatin, or carboplatin, and some were on a chemotherapy regimen of more than one agent. The sponsor just provided the analysis based on this factor, and found a statistically significant reduction in the risk of thromboembolism in only 1 chemotherapy subgroup. Further evaluation is necessary to determine which patients, if any, would derive the most benefit from semuloparin.
The secondary outcome of this study was 1-year survival, and there was no difference between the 2 groups, with 40% mortality in semuloparin patients and 41.5% mortality in placebo. This high mortality rate demonstrates the severity of illness facing these patients, and the importance of determining which patients are most likely to benefit without being subjected to additional harm.
With minimal gains in efficacy over the currently accepted treatment regimen, and with risks that should not be overlooked, particularly noting that the number needed to treat is greater than the number needed to harm, we recommend that semuloparin be studied more extensively prior to approval. Making it available prior to determining whether there are some types of patients who are more likely to benefit could be harmful to many patients, and helpful to few.