Reduced Comparator High Cost for Biosimilars

PROJECT  An executive at a pharmaceutical company asked BBCR to review its biosimilar pre-clinical data, prepare the IND package, and evaluate the innovator approved indications to identify the fastest and safest path to NDA approval.

PROPOSAL  BBCR suggested engaging the FDA in a pre-IND meeting to gain feedback on the preclinical data. BBCR prioritized therapeutic indications in oncology and autoimmune diseases, per the criteria including recruitment of target patients, trial duration, number of patients and cost of trial.

RESULTS  After evaluating the different indications, the BBCR team suggested a phase 3 trial for adjuvant treatment and adoption of a surrogate endpoint that world reduce the number of patients to recruit, length of study, and study cost.

Fast Value Growth for Start-up in Ultra-rare Diseases

PROJECT  A start-up biotech asked Dr. Fratazzi to act as a CMO and for BBCR to provide support with pre-IND clinical strategy for three compounds for ultra rare disease treatment.

PROPOSAL  Dr. Fratazzi and the BBCR team suggested engaging with the FDA in pre-IND meetings to discuss pre-clinical data needed prior to FIM study and adoption of Real World Evidence (RWE) as a comparator arm for Phase III pivotal studies.

RESULTS  The FDA approved the use of RWE to define the individual ultra rare disease Natural History to be adopted as comparator arm in the Phase 3 pivotal study. The start-up was sold, within 9 months from work start, for $ 26.6M plus.

505(b)(2) NDA Path and Improved Safety

PROJECT  A Pharma company, that had invested on developing liposome deliver systems for some specific oncology small molecules, contacted BBCR requesting support to:

  1. identify the regulatory path to approval
  2. evaluate if the new formulation would solve the safety concerns that limited the chemo-therapy market penetration
  3. prioritize the indications for which the originator molecule was approved both as first and second line therapy
  4. explore additional oncology indications
  5. evaluate study feasibility based on patient access and physician interest
  6. run a KOL advisory meeting

PROPOSAL  BBCR reviewed the internal product development plan involving an innovator NDA and clinical trials in one of the indications in which the innovator product was approved. We investigated concern arising from feedback on patient recruitment, the uncertainty of the market share and the complexity of the regulatory path. We analyzed multiple indications compatible with the small molecule’s MOA and performed market analysis.

RESULTS  the opportunity for the liposome pro-drug to satisfy repurposing conditions 505(b)(2) NDA was identified. The pharma team recognized the benefit of a 505(b)(2) filing compared to a regular NDA. BBCR team identified two indications in which the liposome product had an opportunity to succeed in a head to head study design versus approved comparators. During the KOL meeting, patient availability, physician interest, an opportunity for market penetration, and the ability to test the improved safety profile were confirmed.

Granted Orphan Status for a NSCLC Subpopulation

A start-up that was developing a combination product preventing recurrences in resected NSCLC patients contracted BBCR to support replying to the OOPD questions and its third resubmission. The OOPD previously rejected the orphan petition twice due to a lack of incidence and prevalence data for the targeted population.

CHALLENGE  The task was challenging and the BBCR team reviewed the petition with caution. The OOPD asked several questions targeted at circumscribing and limiting the use of the therapeutic device outside the population included in the orphan petition.

SOLUTION  Available data on the incidence and prevalence of the NSCLC was analyzed to address OOPD concerns, and questions were answered with extensive literature support.

RESULTS  The BBCR team organized a call with OOPD to clarify the sponsor’s intention and rationale. The Orphan petition was submitted for the third time and was approved with no additional questions.

Strategy to Avoid Market “Me Too” in Rare Disease

PROJECT  Develop the product avoiding a “me too” treatment in an orphan population when a very similar product had a market monopoly for 15 years.

PROPOSAL  Create a clinical innovative strategy and trial designs that avoid the obvious head to head design, which would require an unfeasible number of patients, and be at high risk to prove efficacy and safety in the rare disease population. The FDA at the IND approved the proposed clinical plan with no modification.

RESULTS  The proposed clinical plan was successful, and the product approved in many countries.

Carla Epps, M.D., MPH, FAAP, Medical Officer FDA/CDER/ONDon May 2011 summarized the clinical strategy stating:

  • Well planned
  • Clinically meaningful endpoints
  • Each trial had a distinct purpose


Biomarker Signature in Rheumatoid Arthritis MTX Responders

PROJECT  One of the most important questions in treating physician’s mind is how to know which patient will respond to which drug in a given disease.

PROPOSAL  Retrospective study in patients with early rheumatoid arthritis to identify a signature able to differentiate responder from no responder to methotrexate. Such a signature would allow for early treatment with biologics in patients not able to respond to first line treatment.

RESULTS  identified the first signature able to predict responders from no-responders RA patients. This is a milestone in precision medicine for RA. Results were published in J Transl Med. 2018; 16: 18. Published online 2018 Jan 29. doi: [10.1186/s12967-018-1387-9]

Address Slow Enrollment in a Rare Disease Trial

PROJECT  A large phase 3 in a rare disease was started to be an USA study only. The peculiarity was that the treating physicians were pulmonologists and study drug indication was pancreatic insufficiency. Quite a number of competing studies were present at the USA sites. Patient enrollment was slow.

PROPOSAL  Opening new sites outside the USA. Evaluate sites interest in the EU and the rest of the world (ROW), patients’ availability and study feasibility based on regional diet. The EU sites had a smaller number of competitive trials, treating both adult and adolescent patients and had less diet variability compared to the USA sites and ROW sites.

RESULTS  Additional EU sites were identified and opened. These sites enrolled about  50% of the total number of patients. Enrollment was completed about one week earlier than originally planned.

Salvage Rare Disease Trial

PROJECT  A Phase 3 study in a rare infectious disease enrolled only 10% of patients in twelve months. The Sponsor had to decide to either change the CRO or close the trial.

PROPOSAL  A gap analysis of the multiple recruitment tools and the numerous opened sites was conducted. The website base recruitment tool showed an inability to connect patients with sites on time. Site interviews indicated that two third of the opened sites either had no direct access to patients or referral networks.

RESULTS  A decision was made to keep the CRO. The website-based recruitment tool was closed as too expensive and inefficient.

Many sites were closed due to cost inefficiency. Sites identified with flawed recruitment systems were closed. The remaining sites were motivated and supported via active and ongoing interactions. During the pandemic year of 2022, Patient recruitment was completed. The study drug showed efficacy and safety in the study and patients will have access to effective therapy

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