Daria G. Husni

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On Oct. 20, 2023 Pfizer announced that PENBRAYA, its vaccine for meningococcal groups A, B, C, W, and Y, has been approved by FDA. According to Pfizer, PENBRAYA is the first and only vaccine to protect against the five most common serogroups that cause meningococcal disease in patients aged 10 through 25. PENBRAYA combines components from two meningococcal vaccines, Trumenba (meningococcal group B vaccine) and Nimenrix (meningococcal groups A, C, W-135, and Y conjugate vaccine). It is administered as a two-dose series given six months apart.

Meningococcal disease is an uncommon but serious illness that can be fatal within 24 hours or cause significant long-term disabilities for survivors. PENBRAYA reduces the number of doses to fully vaccinate individuals against the five most common serotypes of the disease, which Pfizer hopes can increase the number of adolescents and young adults vaccinated. This is substantiated by a report from the US Centers for Disease Control and Prevention (CDC), which stated that combining vaccines into fewer shots could mean a higher rate of adolescents and young adults getting vaccinated on time.

The FDA approval was based on data from Phase II and Phase III trials, which included a randomized, actively controlled, and observer-blinded Phase III trial. The trials assessed the safety and efficacy of PENBRAYA in comparison to current US-licensed meningococcal vaccines, with the goal of determining immunologic noninferiority. The Phase III trial evaluated more than 2400 patients from the United States and Europe.

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PENBRAYA combines components from two meningococcal vaccines, Trumenba and Nimenrix.

FDA Approves Vaccine for Prevention of the Five Most Common Serogroups Causing Meningococcal Disease in Adolescents

On Oct 24, 2023 FDA approved Servier Pharmaceuticals’ Tibsovo (ivosidenib) for the treatment of adults with “relapsed or refractory (R/R) myelodysplastic syndromes (MDS) with an isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.” Ivosidenib is the first targeted therapy approved for this indication. Abbott Laboratories’ RealTime IDH1 was also approved as a companion diagnostic for the selection of R/R MDS patients with an IDH1 mutation.

MDS are a rare form of blood cancers that develop when mutations in bone marrow progenitor cells (cells that form blood) cause inadequate numbers of healthy blood cells. Approximately 60,000 to 170,000 people in the United States suffer from MDS, and about 87,000 new cases are reported each year worldwide. Around 3.6% of MDS patients have an IDH1 mutation.

This new indication is based on an open-label, single-arm, multicenter study of 18 adult patients with relapsed or refractory MDS with an IDH1 mutation. The mutations were found in peripheral blood or bone marrow via a local or central diagnostic test and were later confirmed with the Abbott RealTime IDH1 Assay. The complete or partial remission rate was 39% (7/18), and of the patients who achieved a complete remission, the average time to complete remission was 1.9 months. Of the nine patients who relied on blood or platelet transfusions, six no longer required transfusions after treatment with ivosidenib.

Ivosidenib was previously approved for select adults with freshly diagnosed acute myeloid leukemia (AML), relapsed or refractory AML, and locally advanced or metastatic cholangiocarcinoma. The Abbott RealTime IDH1 was also approved as a companion diagnostic to identify AML patients with an IDH1 mutation for treatment with ivosidenib or Rezlidhia (olutasidenib). Ivosidenib was granted Priority Review designation, under which FDA is prepared to act on an application within six months of the agency determining that the drug would substantially improve the safety or efficacy of treating, diagnosing, or preventing a serious condition. Ivosidenib also received FDA Breakthrough Therapy designation and Orphan Drug designation.

The treatment has received Priority Review designation, as well as FDA Breakthrough Therapy designation and Orphan Drug designation.

FDA Approves Novel Therapy for Rare Form of Blood Cancers

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On Oct 26, 2023 a report was released from CPHI Barcelona on the discussion around the growth of contract manufacturing organizations (CMOs) in the biologics sphere. The biologics demand is anticipated to reach 4400KL by 2027 (2500KL more than in 2022), which accounts for a growth rate of 11.5% each year and a capacity increase to 8400KL. Tara Dougal, Content Director–Pharma at Informa said, “we see this first hand at CPHI Barcelona where demand for bio CMDOs [contract development and manufacturing organizations] and outsourced biological services continue to grow, and we expect this to be one of the fastest areas of growth in the next few years.”

A CPHI panel of experts—chiefly Dawn Ecker, managing director of bioTRAK Database Services and Patricia Seymour, managing director, BioProcess Technology Group—provided analysis. The panel predicted that even with surprise blockbuster approvals like Wegovy, CMO capacity should be accessible for most biotechs in the coming year. But with CMO capacity growing from 35% of available reactors to 45% by 2027, demand could become constrained in the future as more and more biologics commercialize. Ecker noted that resources could tighten considerably if approvals pass for large population diseases such as Alzheimer’s and diabetes, or if cancer checkpoint inhibitors receive approval from regulators and reimbursement by most insurers. “In this instance, demand for capacity could be much higher resulting in capacity constraints particularly for smaller and early-stage biotech innovators,” Ecker commented.

As of the publication of this article, the majority of cell culture capacity is in-house, primarily concentrated within just 10 companies. This capacity, at 54% in 2023, is expected to rise to 57% in 2027. But as CMOs Fujifilm Diosynth and Celltrion make substantial capacity investments, they are predicted to displace two Big Pharma companies in that top 10 (Novartis and Sanofi). Future manufacturing equipment is also changing and becoming smaller—nearly three quarters of recombinant products in late-phase development can currently be produced using a single 2000L or 5000L bioreactor.

As CMOs continue to invest in cell culture capacity, some are expected to surpass top in-house companies.

CPHI Barcelona: CMOs Expected to Account for 45% Available Bio Capacity in 2027

 was released during CPHI Barcelona. This report indicates a rise in biotech funding and subsequent growth for pharma contract services. This year’s CPHI Barcelona reportedly sees the largest gathering of contract development and manufacturing organizations (CDMOs).

Analysis on the report was given by CPHI Report expert Brian Scanlan of Edgewater Capital. According to Scanlan, liquidity in the biotech and mid-sized pharma market is typically a proxy of growth for the contract research organization (CRO)/CDMO sector. Over the past two quarters, funding into the sector has seemingly stabilized at levels last seen right before the pandemic. Total funding in 2023 is trending ahead of 2022, with the exception of initial public offerings (IPOs), which remain weak.

Over the past few years, the spike in market saturation combined with decreased funding led to CDMOs slowing development pipelines. But Scanlan predicts that the market is turning. “There are signs of an improving VC [venture capital] funding environment, but this needs to coincide with increasing pharma M&A and a healthier IPO environment,” he wrote. “We believe softer demand, particularly from emerging pharma and in earlier phases of development, will extend for a period of 12–18 months. However, the investment banking community is already signaling a pickup on deal activity starting in late 2023 and accelerating into 2024.”

The noise around onshoring has slowed, as there are now two competing forces at work. The forces that initially ignited the supply chain re-alignment surge such as COVID-19, geopolitical tensions, and risk mitigation have been partially offset by calming geopolitical tensions, decreasing supply chain disruptions, and renewed focus on cash management (prompted by funding challenges).

Scanlan stated that an important (and positive) factor for CDMOs is the workforce shedding in the industry over 2022 and the early part of 2023, which he predicts will bolster demand for CRO/CDMOs in 2024. He concluded that the long-term fundamentals for CRO/CDMOs are very good, especially given the number of compounds in all phases of development and market dynamics that favor increases in outsourced penetration rates.

The report indicates a rise in biotech funding and subsequent growth for pharma contract services.

CPHI Annual Report: VC Capital Investment and Contract Services Growth in 2024

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On Oct. 17, 2023, Lisata Therapeutics announced that the European Medicines Agency (EMA) granted orphan drug designation to LSTA1, Lisata’s lead product candidate for pancreatic cancer treatment. As of the publication of this article, LSTA1 has several ongoing and planned clinical studies conducted globally. These studies use a variety of solid tumor types, including pancreatic cancer, with a range of anti-cancer regimens.

LSTA1 is an investigational drug intended to aid co-administered or tethered anti-cancer drugs to more effectively penetrate solid tumors by activating a novel uptake pathway. LSTA1 activates the pathway in a tumor-specific way, potentially modifying the tumor microenvironment and making tumors more venerable to immunotherapies. There is significant non-clinical data showing LSTA1 enhancing delivery of a variety of existing and emerging anti-cancer therapies, including immunotherapies, chemotherapeutics, and RNA-based therapeutics.

The orphan drug designation is given to drugs and biologics that treat rare disease, which affect no greater than five in 10,000 people in the European Union. The designation is based on a positive opinion from the EMA Committee for Orphan Medicinal Products. The companies of eligible products receive EU marketing exclusivity for 10 years after approval, possible fee reductions, and protocol assistance from EMA.

“To date, LSTA1 has demonstrated favorable safety, tolerability, and activity to enhance delivery of standard-of-care chemotherapy for patients with metastatic pancreatic cancer,” said Kristen K. Buck, M.D., executive vice president of R&D and Chief Medical Officer of Lisata, in a press release. “Obtaining orphan drug designation from the EMA reinforces our belief that LSTA1 offers major improvement in treating patients with this terrible disease. We are excited by the promise of LSTA1 for the treatment of pancreatic cancer and other solid tumors and are committed to advancing our development programs with the goal of providing a benefit to patients.”

The designation will grant Lisata EU marketing exclusivity for 10 years after approval and protocol assistance from EMA.

Lisata Therapeutics Announces EMA LSTA1 Orphan Drug Designation for Pancreatic Cancer Treatment

Royalty Pharma announced on Oct. 19, 2023 that it has signed an agreement with PTC Therapeutics to acquire additional royalties on Roche’s Evrysdi. Royalty will pay $1.5 billion upfront, with the possibility of purchasing the remaining royalties for up to $500 million at a later date. Evrysdi, which is marketed by Roche, is an “orally administered survival motor neuron-2 (SMN2) splicing modifier for the treatment of spinal muscular atrophy [SMA].” It received FDA approval in 2020 and has since treated more than 11,000 patients internationally. In 2022, Evrysdi generated approximately $1.2 billion in sales, 87% higher than in 2021.

As of the publication of this article, Roche’s royalty payment on Evrysdi is tiered, ranging from 8% to 16%. Following this transaction, Royalty Pharma’s ownership of the Evrysdi royalty is increasing from 43% to 81%. Until Dec. 31, 2025, PTC will have the option to sell its remaining Evrysdi royalties to Royalty Pharma for $500 million in five equal tranches. If PTC uses less than three of these options, Royalty Pharma will have the opportunity until March 31, 2026 to purchase 50% of the remaining royalties for $250 million.

“We are excited to acquire an additional royalty interest in Evrysdi, a convenient, oral therapy that has transformed the lives of SMA patients worldwide,” said Pablo Legorreta, founder and chief executive officer of Royalty Pharma in a Royalty Pharma press release. “This is our second transaction with PTC, which builds on our longstanding partnership, and highlights our ability to structure creative, win-win funding solutions for our partners. Further, our unmatched scale and deep knowledge of SMA positioned us to provide PTC with substantial capital in a timely fashion, another unique aspect of our business model. This transaction is expected to further enhance Royalty Pharma’s long-term growth and diversification. We remain incredibly excited for our future given our robust transaction pipeline.”

The spinal muscular atrophy treatment, currently marketed by Roche, generated $1.2 billion in sales in 2022.