Letter from the Editor: new modalities to decorate your wall

A downloadable chart of approved new modalities for general use

It’s easy, when buried in the books or the balance sheets, to lose sight of the accelerating pace of progress taking place in the biopharma industry.

We’re all aware of the explosion in new technologies, but how many of these make it to market, and what shape is the learning curve?

BioCentury documented the approval of new modality therapies in 2021, charting the first global approvals for drugs based on platforms outside of the now traditional modalities — small molecules, mAbs and standard protein therapeutics.

With the resounding interest that followed, and that resumes each time the graphic is presented, we are making available a version of the chart updated as of July 31, 2022, in downloadable format suitable for printing and display, or incorporation into a presentation. 

The chart contains hyperlinks for each therapy to the product profile in BioCentury’s BCIQ database, which provides information on each product’s development pipeline in the marketed and follow-on indications, its target, and its originator plus any partners. 

The chart shows first approvals globally. Most represent FDA approvals, with those approved first in Europe, China and Japan denoted by asterisks, as indicated. Products in registration are shown with open circles. Products that have been withdrawn, discontinued or given a complete response letter are not shown. Stock tickers or company names represent companies that now market the drug in the territory where first approved.

Download the chart HERE for a printable version with hyperlinks. 

In the 17 months since the first article posted, 11 new modalities have been approved, and eight more are in registration, with bispecifics leading the surge at four new approvals in that time. Gene therapies are arguably poised for the next wave, with four in registration.

Across the technologies, a pattern emerges — antibody-drug conjugates (ADCs) and bispecifics are clear cases in point — that reflects the maturation of a field as it solves the issues still on the path paved by the breakthrough products.

A first approval is often followed by a lag, a second breaks through, and the gaps between the next products generally shorten. For ADCs, the field had to solve issues of toxicity with improvements to linker, payload and antibody technologies that better restrict chemotherapy effects to the tumor. Bispecifics faced delivery and administration challenges, as the original complex biologics required burdensome continuous infusion.

Beyond the technology problems lie commercialization ones, in particular for new modality therapies such as gene therapies and CAR Ts that could be “one and done” treatments. Those dictate the pace of progress as well.

While the number of products is one measure of robustness for a new modality, another indicator of maturity is the number of players. ADCs, pioneered by  Seagen Inc. (NASDAQ:SGEN), have many competitors, though Seagen remains a dominant force. 

Bispecifics and gene therapies likewise have many parents, and in both cases the next few years should see more products reach the market. Next-generation bispecifics were plentiful at the American Society of Clinical Oncology (ASCO) meeting in 2021.

Gene therapies have a slew of candidates under review from multiple sponsors, and that field is grappling with a year of setbacks, addressing translational challenges, and building the next generation of the technology. 

Antisense has fewer players, with pioneer Ionis Pharmaceuticals Inc. (NASDAQ:IONS) still a heavyweight, and for RNAi, Alnylam Pharmaceuticals Inc. (NASDAQ:ALNY) dominates — although Leqvio inclisiran is marketed by Novartis AG (SIX:NOVN; NYSE:NVS), it originated at Alnylam. Both Alnylam and Ionis locked down the IP early, so it’s interesting to note that these modalities don’t follow the same lag pattern. Licensing deals put the technologies in the hands of others who could help advance them, but those innovator companies commanded the march to the market.

CAR Ts have, arguably, made the biggest splash of all, yet struggle with technology limitations to make them widely accessible and deployable in solid tumors. The patient-specific, autologous cell therapies raise CMC and market access issues that could be addressed with allogeneic formats, once allogeneic durability issues are solved. But CAR Ts are making the move into earlier lines of treatment despite access barriers, and preclinical advances are expanding the toolbox. 

In several cases, new modalities vie over specific targets, such as CD19 and TIGIT in cancer, transthyretin (TTR) for treatment of the rare disease TTR-mediated amyloidosis (ATTR), SMN2 to treat spinal muscular atrophy and dystrophin to treat Duchenne muscular dystrophy.

More new modalities will likely reach the market in the next few years — NK and TCR-based cell therapies are in Phase II, and are likely next in line. Cell therapies created with ex vivo editing aren’t far behind, with several programs reporting promising Phase I results. mRNA’s success in vaccines awaits extension to therapeutics, and the gene editing faithful will hope that in vivo version of the technology can reach patients before too long, with all eyes on the Phase I ATTR program from  Intellia Therapeutics Inc. (NASDAQ:NTLA).

The longer-view hope is that in vivo editing will displace ex vivo edited cell therapies for sickle cell disease, β thalassemia and even CAR T cells to cut out dangerous conditioning regimens.