Do Drug Regulatory Body Advices or help Pharmaceutical Companies in regulatory process or product approval process

Yes, Almost all Regulatory bodies offer pharmaceutical companies opportunities for early discussions about their products’ development and regulatory pathway. Many time they provide assistance and and critical paths which companies should follow for approving their product.

The European Medicines Agency (EMA) offers SMEs access to administrative and procedural assistance, as well as fee reductions and waivers for scientific advice. The agency believes that providing these incentives to SMEs can support the development of innovative new products.

Some HTA bodies have recently begun to offer advice to companies. However, the survey found few instances of HTA bodies providing scientific advice, and even fewer instances of advice being provided to SMEs.

One of the main issues the report seeks to address is the fact that some drugs are not authorized—not because of their effectiveness, but because they failed to meet regulators’ data requirements. To address this issue, regulators offer scientific advice to companies to aid them in designing their clinical programs.

Let us look into the recent case where pharmaceutical companies received specific advice from regulator!

Molecule: Tecarfarin

Tecarfarin is being investigated for use as an oral, once-daily anticoagulant that inhibits Vitamin K epoxide reductase (VKOR), an important enzyme in the coagulation system, and avoids CYP450 metabolism and renal elimination. In Phase 2 and Phase 2/3 (EMBRACE-AC) clinical testing, tecarfarin improved time in therapeutic range (TTR) in chronically anticoagulated patients. The effect of tecarfarin on TTR will be further investigated in the Company’s upcoming pivotal clinical trial, TACT (Tecarfarin for AntiCoagulation Trial), which will be conducted under a Special Protocol Assessment agreed upon with the FDA. TACT is an open-label trial expected to enroll 1,000 patients with any indication for anticoagulation, including prosthetic heart valve (PHV) patients. TTR was chosen as the primary endpoint for TACT on the basis of evidence suggesting that better anticoagulation control (as measured by higher TTR) can protect patients from severe or even fatal adverse events. Tecarfarin is monitored using INR (International Normalized Ratio) and is being investigated for use without the need for CYP2C9 genotyping since tecarfarin is not metabolized via the CYP450 system. In preclinical and early clinical studies, the anticoagulant effect of tecarfarin was reversed by existing and readily available antidotes for Vitamin K Antagonists.

Armetheon, Inc., a specialty pharmaceutical company developing novel small molecule drugs for cardiovascular diseases, received advice from the European Medicines Agency (EMA) Scientific Advice Working Group (SAWG) for the development of its novel oral anticoagulant tecarfarin. The SAWG advised that Armetheon can conduct a single 1000 patient pivotal study prior to filing the Market Authorization Application (MAA) for tecarfarin. If approved, tecarfarin is positioned to potentially be the oral anticoagulant (OAC) therapy of choice for patients who require anticoagulation with a vitamin K antagonist (VKA), such as warfarin. This includes patients with prosthetic heart valves (PHV), repeat deep vein thrombosis or patients with chronic kidney disease (CKD) which complicates anticoagulant therapy. This pivotal trial will enroll patients with all indications for anticoagulation, thereby supporting a potential broad label if the product is approved. 

“The advice received from the EMA-SAWG for the conduct of a single 1000 patient final Phase 3 study prior to a potential MAA filing allows for a global harmonization of our development plan for tecarfarin,” said Armetheon’s President & interim CEO, M. (Ken) Kengatharan, PhD. “The primary end point for approval is time in therapeutic range (TTR) of the international normalized ratio (or INR), an outcome measure, which indicates how effectively anticoagulation is managed in a particular patient receiving a VKA and has now been accepted by the EMA, FDA and the PMDA.”