Biogen’s Aduhelm Marketing and Approval are Under Scrutiny in New FTC and SEC Investigations

Biogen can’t seem to get a break when it comes to the Alzheimer’s disease drug Aduhelm. Along with limited sales and a constraining Medicare coverage plan, the medicine is now facing additional scrutiny as part of a pair of US government investigations.

The Federal Trade Commission (FTC) and the Securities and Exchange Commission (SEC) have opened separate inquiries into Biogen and its troublesome Alzheimer’s drug.

The Federal Trade Commission has issued a civil investigative demand, which is similar to an administrative subpoena, for records connected to Aduhelm’s marketing and approval and healthcare sites. Meanwhile, the SEC has opened a separate investigation into the anti-amyloid antibody’s marketing and clearance.

Last August, Biogen received accelerated approval for Aduhelm, but the FDA decided on a surrogate endpoint removing amyloid plaques rather than slowing cognitive deterioration. The FDA’s decision came despite a resounding “no” from the FDA’s advisory group on Aduhelm’s clearance.

This isn’t the first time Aduhelm has been investigated. In June, the House Committee on Oversight and Reform said that it would investigate the drug’s contentious approval and cost. The drug was initially priced at USD 56,000, but Biogen later reduced the price to USD 28,200 for a patient of average weight.

Aduhelm’s shaky launch has also resulted in low sales. The drug only made USD 1 million in the fourth quarter of 2021 and USD 3 million for the whole year. That’s a huge drop when compared to the hundreds of millions of dollars in sales, general, and administrative costs the company has paid thus far on the same medication.

Sanofi’s Enjaymo has Finally Received FDA Approval for a Rare Blood Disorder

Patients with Cold Agglutinin Disease, a rare blood disorder, now have a medication that can help them reduce the number of blood transfusions they need. Sanofi’s Enjaymo (sutimlimab) was authorized by the FDA on February 04 for hemolysis, or the disintegration of red blood cells, which is a symptom of the condition. Enjaymo is the first authorized medication for CAD.

Winning approval for sutimlimab will allow Sanofi to repay part of the USD 11.6 billion (€10.5 billion) it paid for Bioverativ in 2018. Bioverativ bought Sutimlimab in 2017 for more than USD 400 million from True North Therapeutics.

Sutimlimab, a monoclonal antibody, was scheduled for FDA approval in 2020. However, in November of that year, the agency sent a comprehensive response letter to Sanofi, citing problems found during an inspection of a contract manufacturer’s facility. The rejection was free of any clinical or safety flaws.

Enjaymo is administered intravenously in weekly dosages for the first two weeks, then every two weeks after that. It costs USD 1,800 per vial before discounts, and the dose is determined on body weight. The annual cost for a patient weighing between 39 kg (85 pounds) and 75 kg (165 pounds) would be USD 280,000 after the treatment was established. Enjaymo is also awaiting clearance in Europe and Japan.

NHS Agreed to a Deal With Orchard For the Costly Libmeldy Gene Therapy

The National Health Service England (NHS England), one of the pillars of four National Health Service systems in the United Kingdom has agreed to a confidential deal with Orchard Therapeutics. This deal will allow access to Libmeldy that is a gene therapy for a rare childhood disease considered to be the most expensive drug in the world. In December 2020, it was approved by the European Commission for Metachromatic Leukodystrophy treatment. In last year’s July, Libmeldy was rejected for NHS use by NICE because it was too expensive. But after a second confidential price reduction, it will be available for children in Wales and England for Metachromatic Leukodystrophy (MLD) treatment.

Libmeldy will be available as a one-shot therapy with pricing of nearly 2.8 to 2.9 million euros per patient treatment. MLD is a hereditary neurodegenerative disorder which is caused due to deficiency in the ARSA gene. This gene encodes for enzyme arylsulfatase-A because of which sulphatide compounds build up in the body. Metachromatic Leukodystrophy symptoms include loss of ability to detect sensations, such as pain, touch, sound, and heat, loss of motor skills, loss of memory skills, intellectual thinking, etc. Libmeldy treatment will allow stem cell harvest from bone marrow or blood of patients, and replace defective ARSA gene with a more functional version, afterward reintroduce them again inside the body by a single intravenous infusion.

So, now the deal between NHS and Orchard will lead the treatment for some of the children who are born with Metachromatic Leukodystrophy in England.

Bristol is Busily Raising the Supply of Breyanzi and Abecma as the Big Revlimid Patent Cliff Looms

Bristol Myers Squibb has launched two very successful CAR-T products, Breyanzi and Abecma, and now scaling up for the manufacturing front to meet early demand as Abecma’s supply shortfall was experienced last year. Breyanzi main focus currently is vector supply as they had a short supply as well.

In addition to fully scaling up Breyanzi and Abecma production BMS is also gearing up for three new drug debuts in 2023 to combat the loss of exclusivity faced by their megablockbuster drug Revlimid for Multiple Myeloma. These three planned 2023 launches are novel combinations for oncology – Relatlimab plus Opdivo, Mavacamten for obstructive hypertrophic cardiomyopathy treatment, and Deucravacitinib for Plaque Psoriasis treatment. Opdivo is a very successful immuno-oncology drug launched by Bristol Myers Squibb.

Lastly, BMS’ chief financial officer David Elkins stated that even after potential expense cuts due to the Revlimid loss of exclusivity, BMS is fortunate to be able to reallocate resources to new launches.

Pharming is Preparing to File for Leniolisib, a Rare Disease Medicine

The European Commission has granted orphan drug status to Leniolisib to treat Activated Phosphoinositide 3-Kinase Delta Syndrome (APDS), based on a positive assessment from the European Medicine Agency’s Committee for Orphan Medicinal Products (COMP). The US Food and Drug Administration (FDA) approved Leniolisib Orphan Drug Designation in January 2018 for “the treatment of Activated PI3K Syndrome or p110-activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency.” Following regulatory clearance, the European Commission’s orphan medicine classification gives specific regulatory procedural and financial incentives, including, but not limited to, ten years of product-market exclusivity in the EU.

An investigational drug must be intended to treat a life-threatening or chronically debilitating condition that affects fewer than five out of every 10,000 people in the EU. The treatment must significantly benefit those affected by the condition, or there must be no satisfactory treatment available.

Activated phosphoinositide 3-kinase-delta (PI3K) syndrome (APDS) is caused by PI3K activating mutations in the PIK3CD (Type 1 APDS) or PIK3R1 (Type 2 APDS) genes. PASLI-CD and PASLI-R1 are synonyms for Type 1 and Type 2 APDS. The p110-activating mutation that causes senescent T cells, lymphadenopathy, and immunodeficiency are known as PASLI. APDS is a hereditary primary immunodeficiency illness that causes recurrent and/or severe bacterial and viral infections, chronic benign lymphoproliferation, and/or autoimmune disease. The global incidence rate of APDS is now estimated to be between 1-2 per million. In individuals with a compatible phenotype, such as immunodeficiency and lymphoproliferation of unclear origin, the diagnosis of APDS is achieved by sequencing the genes PIK3CD and/or PIK3R1.

Leniolisib is a small molecule inhibitor of phosphoinositide 3-kinase delta (PI3K) with immunomodulatory and anti-neoplastic properties. Phosphatidylinositol-3-4-5-trisphosphate production is inhibited by leniolisib (PIP3). PIP3 is an essential cellular messenger that affects various cell processes, including proliferation, differentiation, cytokine secretion, cell survival, angiogenesis, and metabolism by activating Akt (through PDK1).

During the first-in-human experiment and the continuing open-label extension phase, leniolisib was found to be safe and well-tolerated in healthy participants and APDS patients.

Verzenio’s Phase 3 HER2-Positive Early Breast Cancer Trial Has Been Canceled by Eli Lilly

Eli Lilly and Company released updated data from the Phase 3 monarchE study, which looked at the investigational use of Verzenio (abemaciclib) in combination with standard adjuvant endocrine therapy (ET) for the treatment of HR+, HER2-, node-positive, high-risk early breast cancer (EBC). These findings were presented at today’s ESMO Virtual Plenary and published in the Annals of Oncology at the same time.

monarchE met its first endpoint of a statistically significant improvement in invasive disease-free survival in the intent-to-treat population for patients treated with adjuvant Verzenio plus endocrine therapy compared to those treated with ET alone, according to findings published in the Journal of Clinical Oncology. According to professional criteria, invasive disease-free survival (IDFS) was defined as the time between breast cancer recurrence, the development of new malignancy, and death.

Women and men with HR+ HER2-, node-positive early-stage breast cancer with a high probability of disease recurrence based on clinical and pathological characteristics were included in the study. The patients were divided into two groups. Patients in Cohort 1 had 4 or 1-3 positive axillary lymph nodes (ALN) with either Grade 3 illness or a tumor size of less than 5 cm. Patients in Cohort 2 had 1-3 positive ALN and a centrally confirmed Ki-67 score of less than 20%. (defined in the study as “Ki-67 high”). Ki-67 is a cellular proliferation marker. In Cohort 1 patients with a sufficient sample, the Ki-67 score was also assessed centrally, but it was not needed for enrollment in this cohort. Both Cohort 1 and Cohort 2 were represented in the ITT population.

“The results from monarchE are truly remarkable, and we are encouraged by the consistency of the treatment benefit and rising magnitude of effect observed over time in reducing the exposure of recurrence & development of metastatic disease,” said Joyce A. O’Shaughnessy, M.D., monarchE investigator and presenter at today’s ESMO Virtual Plenary. “These findings show that adding adjuvant Verzenio to endocrine therapy in high-risk early breast cancer patients could change the way we treat them and could fill a large unmet need for those with clinical and pathological risk factors which need additional treatment options.”

The HR+ HER2- subtype accounts for almost 70% of all breast malignancies. Verzenio abemaciclib is a CDK4/6 inhibitor that is used to treat cancer. Verzenio is an oral tablet that is not used for chemotherapy. Verzenio works inside the cell to prevent CDK4/6 activity, and aids cancer cells to stop growing so they can die (based on preclinical studies). Binding to D-cyclins activates cyclin-dependent kinases (CDK)4/6. Cyclin D1 and CDK4/6 enhance retinoblastoma protein (Rb) phosphorylation, cell cycle progression, and cell proliferation in estrogen receptor-positive (ER+) breast cancer cell lines.

Verzenio is Lilly’s first solid oral dosage form created using continuous production, a speedier, more efficient method. Lilly is one of the first firms to adopt continuous production, a novel and advanced form of manufacturing in the pharmaceutical sector.

UCB Preparing to File Another challenger to AZ’s Soliris

In another latest developments in the clinical trials segment, the Belgian-based global biopharmaceutical company UCB announces the positive data in RAISE (NCT04115293) trial for its investigational treatment zilucoplan for Myasthenia Gravis.

Zilucoplan is a self-administered, subcutaneous (SC) peptide inhibitor of complement component 5 (C5 inhibitor), and it met the primary & secondary endpoints with statistical significance in adults with generalized Myasthenia Gravis (gMG). The UCB announce that the  zilucoplan was well-tolerated & no major unexpected safety findings were identified compared to earlier zilucoplan studies. The incidence of serious treatment-emergent adverse events (TEAEs) in the zilucoplan and placebo treatment arms were similar. UCB is expected to present the detailed Phase 3 trials results at forthcoming medical meetings later this year. With the success of the result, the UCB is planning to file for the approval of the zilucoplan in the United States (US), European Union (EU), and Japan, later this year. 

Earlier, last year in November 2021, UCB announces positive Phase 3 trials results for rozanolixizumab in patients with generalized Myasthenia Gravis (gMG). UCB  is the only company in the segment with two potential treatments with different mechanisms of action. Currently, AstraZeneca with its’ gMG therapy Soliris (eculizumab), is leading the gMG Therapeutic market. The approval of the UCB’s emerging therapies is expected to give a tough competition to AstraZeneca in the gMG treatment landscape.

Eli Lilly Delays Alzheimer’s Drug (Donanemab) Filing in Response to CMS’s Latest Decision

Eli Lilly has dropped the decision to file accelerated approval of its Alzheimer’s drug donanemab in the first quarter of this year. As per the earlier update, Lilly was supposed to complete the application for speedy approval of donanemab, based on the results of its TRAILBLZAR-ALZ study. In Trailblazer-Alz trial, donanemab decreased beta-amyloid levels on average by almost 80%. Now, Lilly is hope to complete the filing of the application for accelerated approval to the Food and Drug Administration (FDA) by the end of this year.
In January 2021, the U.S. Centers for Medicaid and Medicare Services (CMS), as per its draft National Coverage Determination (NCD), has limited the coverage for Alzheimer’s drugs, including Biogen’s controversial drug Aduhelm (aducanumab), only to patients taking part in approved clinical trials. The CMS decision is anticipated to have a significant impact on the market success of Alzheimer’s pipeline therapies. Apart from Lilly, other companies in the Alzheimer’s therapeutics segment, are keenly observing the segment and are likely to take further action with their pipeline therapies till the final decision is expected from CMS in April. Roche and Eisai are other major companies in the Alzheimer’s market with their therapies in different stage of clinical trials.