Speaker: Dr. Charles Lynde
*This is not a transcript, but a summary of the Drug Update at the Dermatology Update Fall 2020 in Vancouver, our first hybrid conference.
Dermatology Update is a therapeutics-focused conference and as such we have a tradition of starting off with a drug update, an overview of the most promising drugs that have hit the market or are currently undergoing clinical trials at various stages. As pharmaceutical companies, dermatologists, and GPs, we all need to understand and adapt to the changing market as innovation is rapid in our field. The three therapies we will be looking at are small molecules, biologics, and topicals.
- As of Nov. 2, 2020, there were 1989 Active, Upcoming, and Recruiting trials for vaccines, of which 273 are for COVID-19.
- Vaccines are relevant in dermatology. Dermatologists are likely to advocate for vaccines such as Shingrix.
Pfizer is at the forefront of this push.
- Dupilumab has been a new weapon against atopic dermatitis, improving patient lives. It’s also being investigated for other indications such as chronic hand eczema, bullous pemphigoid, and prurigo nodularis.
- Clinical trials for atopic dermatitis are on the increase as well. There were 855 clinical trials in Nov 2019, compared to 961 clinical trials in 2020.
- Dermatologists are becoming immunologists more and more. Barrier defects, immune defects, the microbiome, and their interplay are being studied.
- IL-33 Inhibitor (ANB 0202) by Anaptysbio, OX40s like GBR 830 (Glenmark) and KHK4083 (Kyowa) are also being studied.
- Tralokinumab IL13 Inhibitor (LEO Pharma) and Lebrikizumab IL13 Inhibitor) (Demira) and Nemolizumab, an IL31 Inhibitor (Galderma), represents the biologics developments for atopic dermatitis.
- Tezepelumab (Amgen), a TSLP inhibitor, did not meet primary endpoints for atopic dermatitis but is still being looked at for other indications like asthma, COPD, Bronchial disease, and chronic spontaneous urticaria.
- JAK inhibitors are also on the rise – Abrocitinib JAK-1 Inhibitor (Pfizer), Baricitinib JAK-1 and 2 (Ellie Lily), Brepocitinib (Pfizer), LPO190 (H4 inhibitor) (LEO Pharma), Upadacitinib (Abbvie), ZPL 389 are all showing promise.
- Topicals are also being developed and studied: Crisaborole (PDE-4 inhibitor), Delgocitinib (JAK inhibitor), INCB18424 (JAK Inhibitor), PF-07038124 (JAK inhibitor).
- Psoriasis has a high burden of disease, but treatment is improving rapidly. Biologics, in particular, has come a long way since Etanercept in 2005 started the path. We’ve moved from PASI 70s to PASI 90s. Our understanding of immunology is getting better, and expectations are growing.
- The market seems to be moving from TNF blockers to IL17s and IL23s. IL23s appear not to have many side effects such as inflammatory bowel and candidiasis.
- Tildrakizumab (SunPharma) 2018 FDA – hoping for 2021 in Canada – tends to be durable for longer.
Mirikizumab (Eli Lilly), an IL-23 inhibitor, is coming soon.
- Bimekizumab, an IL-17A and IL17F inhibitor (UCB), also has high efficacy rates, especially in the PASI 90 range.
- In the small molecules: Apremilast, BMS-98165 (JAK), Brepocitinib (TYK1, TYK2), Tofacitinib, and PF06826647 are interesting.
- For topicals: Tapinarov 1% cream (Dermavant), an AhR modulating agent, Brepocitinib (Pfizer), Halobetasol Propionate, and Tazarotene (Bausch Health) are being studied.
- Palmoplantar pustulosis is a chronic skin condition. Its burden on quality of life is significant. It is not a common disease, but there are unmet needs here.
- IL-36 inhibitor ANB019 (Anaptysbio) is studied for palmoplantar pustulosis and generalized pustular psoriasis.
- Hidradenitis suppurativa causes painful lumps to form under the skin and has a high burden on patients.
Abbvie was the first to take this relatively rare disease on.
There is slow but increasing interest – we’ve gone from 32 active trials in 2019 to 53 active trials in 2020. TYK and JAK are the focus. Ruxolitinib (JAK1 and JAK2) is also being studied.
- Hand dermatitis is another problem that can impact the quality of life and interfere with work in some cases.
JAKs and TYKs are being used for several indications, including hand dermatitis.
- ARQ-252, a JAK-1 inhibitor (Arcutis), is being looked at for hand dermatitis and a number of other indications.
JAKs and TYKs are on the rise and are looking to be the next boom.
- Delgocitinib (LEO Pharma) also targets JAK and is being studied for hand dermatitis cases.
- Safe to say that almost everyone has acne.
- Trifarotene Cream (Galderma), RAR-y (also beneficial for back, shoulders, chest)
- Tretinoin 0.05%+ Benzoyl Peroxide 2.5% (Bausch Health)
- IDP 126 Clindamycin + Adapalene (Bausch Health) may offer a better delivery system
- Tazarotene lotion 0.045%
- Clascoterone (Cassiopea) Androgen receptor inhibitor (also being looked at for androgenic alopecia topical)
- More skin cancer treatments are being developed.
- Methyl aminolevulinate (Galderma) for AKs, BCCs, SCC in situ.
- Sonidegib (Sun Pharma) for BCCs using the hedgehog pathway inhibitor
- Several melanoma products under investigation: Dabrafenib (BRAF Enzyme inhibitor), Vemurafenib (BRAF Enzyme inhibitor), Cobimetinib (MEK-1, MEK-2 inhibitor), Trametinib (MEK-1, MEK-2 inhibitor), LY3022855 (CSF-1R Inhibitor)
- Exciting developments for skin cancer, particularly for melanoma, give patients new hope, and the outlook is much brighter today than it was in the past.
- Vitiligo is another common problem that impacts patients.
- Ruxolitinib is a selective JAK inhibitor. It’s well-tolerated and has produced significant repigmentation.
- Patience is required as it takes time for the melanocytes to respond. No serious adverse events were reported.
- Cerdulatinib Gel DMVT 502 (Dermavant) for segmental vitiligo is also a JAK inhibitor.
- PF-06651600 & PF-06700841 (Pfizer) are also being studied.
- Alopecia was the big success story in 2020.
- Alopecia Universalis – when the hair for the entire scalp is lost, there are a lot of comorbidities, including chronic depression, anxiety, as well as concerns with other autoimmune diseases.
- We haven’t had a lot of great therapies until recently. We’ve tried methotrexate, and steroids with limited success.
- JAKs are being looked at again. CTP-543 Ruxolitinib (Concert) effectively regrows hair, with only minor side-effects (increased CPK levels, some acne in some patients).
- Prurigo nodularis is a common problem related to itching. Itch is a high burden symptom to the patient.
- IL-33 is being looked at for PN (Nemolizumab) and IL-4 and IL-13s as a target.
- For Notalgia Paresthetica, Difelikefalin, a KOR Agonist, is being studied.
- Urticaria is another common patient concern.
- Bilastine (Aralez) is a selective H1 inhibitor for chronic spontaneous urticaria (also for seasonal allergic rhinitis).
- Rupatadine is a PAF inhibitor and a selective H1 inhibitor used for urticaria as well.
- Ligelizumab (Novartis) IgE and Mepolizumab (GSK) IL-5 are being studied, and LY 3454738 (Eli Lilly), CD 200R monoclonal antibody agonists are also being looked at, as well as Remibrutinib (Novartis).
- Lidocaine + Tetracaine 7%/7% (Crescita) for better pain relief is being studied.