Target to $11 from $24
Tuesday, February 1, 2022
Sio Gene accepts reality
Sio Gene Therapies, the biotech famously once known as Axovant, has not had a happy time. Last October it revealed a promising early clinical update from its GM1 gangliosidosis gene therapy, but since then its valuation has halved. With the group now trading at cash drastic action was needed, and yesterday came the defenestration of its chief executive, cancelling of a Parkinson’s disease deal with Oxford Biomedica, and tightened focus on the gangliosidosis projects AXO-AAV-GM1 and AXO-AAV-GM2. At the end of 2021 Sio had $82m of cash, which will now last beyond mid-2023. The Oxford deal, covering AXO-Lenti-PD, had been signed in 2018 when the then-Axovant was worth nearly 20 times more than now and aimed to become a “world-leading innovative neurology company”. With Parkinson’s becoming a competitive area it makes sense to leave the heavy lifting to bigger players, and GM1 and GM2 gangliosidosis look like niches better suited for Sio. AXO-Lenti-PD’s dose-escalation Sunrise-PD trial was to resume this year, but the sham-controlled Explore-PD never got under way in 2021 as planned, and Oxford now needs to find another partner to take it on. The project’s earlier iteration, Prosavin, was canned after generating weak efficacy.
| Selected gangliosidosis gene therapies in the clinic | |||
|---|---|---|---|
| Project | Company | Description | Study |
| GM1 gangliosidosis | |||
| AXO-AAV-GM1 | Sio Gene Therapies | AAV9 vector; IV delivery | NCT03952637 |
| PBGM01 | Passage Bio | AAVhu68 vector; ICM delivery | Imagine-1 |
| LYS-GM101 | Lysogene | AAVrh10 vector; ICM delivery | NCT04273269 |
| GM2 gangliosidosis (Tay-Sachs disease, AB variant & Sandhoff disease) | |||
| TSHA-101 | Taysha Gene Therapies | AAV9 vector; intrathecal delivery | NCT04798235 |
| AXO-AAV-GM2 | Sio Gene Therapies | AAVrh.8 vector; ICM/intrathecal delivery | NCT04669535 |
| Note: ICM=intra-cisterna magna. Source: Evaluate Pharma & clinicaltrials.gov. https://www.evaluate.com/vantage/articles/news/deals-snippets/sio-gene-accepts-reality | |||
Anavex Rett hit says nothing about blarcamesine’s effect size
The white space of Rett syndrome might soon have not one but two approved therapies. At least this is the bull case for Anavex, whose blarcamesine today appeared to score a phase 3 success, just as Acadia did with trofinetide. However, close reading reveals that the Anavex study’s endpoints were changed, likely recently, and it is anyone’s guess what the FDA will say about this. The trial in question, Avatar, previously sought to show blarcamesine’s absolute effects from baseline, versus placebo, on RSBQ and CGI-I scores; but today it was revealed that these took the form of “area under the effect curve” responder analyses that, while ostensibly positive, revealed nothing about the project’s effect size. Sceptical investors, who today sent Anavex down 18%, pointed to Avatar’s clinicaltrials.gov entry, showing that the change had been made just 14 days ago, though Anavex insisted it had done this earlier. The company also claims that “statistical significance alone [is] not sufficient for determining whether an individual patient experienced a meaningful clinical benefit” – a criticism made in December of the relatively small effect sizes seen with Acadia’s trofinetide. Blarcamesine’s paediatric Rett study, Excellence, yet to read out, now apparently also uses AUC measures.
| The changing endpoints of Anavex's pivotal blarcamesine studies | ||||
|---|---|---|---|---|
| Trial | Design | Date | Selected efficacy endpoint | Result |
| Avatar | Adults, quadruple blinded vs placebo | Pre Jan 18, 2022 | RSBQ baseline to 7wk (secondary) | Not disclosed |
| CGI-I baseline to 7wk (secondary) | ||||
| Post Jan 18, 2022 | RSBQ AUC responder analysis (primary) | 72.2% vs 38.5% (p=0.037) | ||
| CGI-I AUC responder analysis (secondary) | 72.2% vs 38.5% (p=0.037) | |||
| Excellence | Paediatrics, quadruple blinded vs placebo | Pre Sep 27, 2021 | RSBQ baseline to 12wk (primary) | Primary completion May 2022 |
| RSBQ AUC responder analysis (primary) | ||||
| Pre Sep 27, 2021 | CGI-I baseline to 12wk (primary) | |||
| CGI-I baseline to 12wk (secondary) | ||||
| Source: clinicaltrials.gov. Note: RSBQ=Rett Syndrome Behaviour Questionnaire; CGI-I=Clinical Global Impression-Improvement; AUC=area under the curve. https://www.evaluate.com/vantage/articles/news/trial-results-snippets/anavex-rett-hit-says-nothing-about-blarcamesines | ||||
FDA approval tracker: January
Roche’s bispecific antibody Vabysmo swayed the regulators last month, but now has to make headway in a competitive space dominated by Regeneron and Bayer’s Eylea. Vabysmo was approved for both wet age-related macular degeneration and diabetic macular oedema, with Roche hoping to exploit the therapy's less frequent dosing. However, Regeneron/Bayer have their defences ready: data on a higher dose version of Eylea are due in the second half of the year. Elsewhere the FDA dished out complete response letters for Pfizer/Opko’s somatrogon and Merck & Co’s gefapixant. The latter is a P2X3 receptor antagonist being tested in chronic cough, and the knockback came as regulators requested further information on efficacy. Bellus Health’s competing project BLU-5937 has had its ups and downs in early trials, but phase 3 will be the real test, with studies due to start this year.
| Notable first-time US approval decisions in January | ||||
|---|---|---|---|---|
| Project | Company | Indication(s) | 2026e sales by indication ($m) | Outcome |
| Spikevax | Moderna | Prevention of Covid-19 (18 years of age and older) | 3,686 | Approved (gained EUA Dec 2020) |
| Vabysmo (faricimab) | Roche | wAMD, DME | 1,129 | Approved |
| 177Lu-PSMA-617 | Novartis | Radioligand therapy for mCRPC | 851 | No decision yet, guided to H1 |
| Cibinqo | Pfizer | Atopic dermatitis | 760 | Approved |
| Quviviq (daridorexant) | Idorsia | Insomnia | 531 | Approved |
| Somatrogon (hGH-CTP) | Pfizer/Opko | Growth hormone deficiency | 113 | CRL |
| Oteseconazole (VT-1161) | Mycovia | Recurrent vulvovaginal candidiasis | - | Not yet disclosed |
| Zonisamide oral suspension | Azurity/Eton | Partial seizures in patients with epilepsy | - | Not yet disclosed |
| Ryaltris nasal spray | Glenmark/ Hikma | Seasonal allergic rhinitis | - | Approved (CRL in 2019) |
| Gefapixant | Merck | Refractory chronic cough or unexplained chronic cough in adults | - | CRL (additional info related to efficacy) |
| Kimmtrak (Tebentafusp/IMCgp100) | Immunocore | HLA-A*02:01-positive unresectable or metastatic uveal melanoma | - | Approved (~1 month early) |
| Source: Evaluate Pharma & company releases. | ||||
| Supplementary and other notable approval decisions in January | |||
|---|---|---|---|
| Product | Company | Indication (clinical trial) | Outcome |
| Lynparza | Astrazeneca | Adjuvant Brca-mutated Her2-negative breast cancer (OlympiA) | No decision yet, guided to Q1 |
| Fasenra | Astrazeneca | Nasal polyps | No decision yet, guided to H1 |
| Rinvoq | Abbvie | Refractory, moderate to severs atopic dermatitis in adults and children aged 12 and over (Measure Up 1 & 2, AD Up) | Approved |
| Skyrizi | Abbvie | Active psoriatic arthritis (Keepsake-1 & Keepsake-2) | Approved |
| Veklury | Gilead | Certain non-hospitalised adults and paediatric patients for the treatment of mild-to-moderate Covid | Approved |
| Olumiant | Lilly | Atopic dermatitis (Breeze-AD programme) | Potential for CRL |
| Libtayo | Regeneron/ Sanofi | Recurrent/met cervical cancer whose disease progressed on or after chemotherapy (Empower-Cervical 1) | Withdrawn |
| Source: Evaluate Pharma & company releases. https://www.evaluate.com/vantage/articles/insights/nme-approvals-snippets/us-fda-approval-tracker-january | |||
GSK Announces Settlement Between Viiv Healthcare, Gilead Sciences
GSK ANNOUNCES SETTLEMENT BETWEEN VIIV HEALTHCARE, GILEAD SCIENCES
* GSK - SETTLEMENT RESOLVES LITIGATION RELATING TO BIKTARVY AND VIIV'S DOLUTEGRAVIR PATENTS AND ENTRY INTO A PATENT LICENCE AGREEMENT
* GSK - GILEAD WILL MAKE AN UPFRONT PAYMENT OF $1.25 BLN TO VIIV HEALTHCARE IN Q1 OF 2022
* GSK - GILEAD WILL ALSO PAY A 3% ROYALTY ON FUTURE US SALES OF BIKTARVY
* GSK - GILEAD'S OBLIGATION TO PAY ROYALTIES DOES NOT EXTEND INTO ANY PERIOD OF REGULATORY PAEDIATRIC EXCLUSIVITY
* GSK - GILEAD WILL ALSO PAY A 3% ROYALTY ON FUTURE US SALES OF BIKTARVY
* GSK - GILEAD WILL ALSO PAY A 3% ROYALTY ON FUTURE US SALES OF BIKTARVY
* GSK-FUTURE ROYALTY INCOME WILL BE RECORDED IN CO'S TOTAL AND ADJUSTED RESULTS IN THE INCOME STATEMENTS FOR 2022 TO 2027 INCLUSIVE
* GSK - VIIV HEALTHCARE, GSK AND SHIONOGI HAVE ALSO AGREED NOT TO ENFORCE THEIR PATENTS AGAINST ANY FUTURE PRODUCT CONTAINING BICTEGRAVIR
Biogen Exercises Option to Participate in Development, Commercialization of Late-Stage Bispecific Antibody
- Biogen Inc. (Nasdaq: BIIB) today announced that it exercised its option to participate in the development and commercialization of mosunetuzumab. Biogen will pay a $30 million one-time option fee to Genentech, a member of the Roche Group, as part of the companies’ long-standing collaboration on antibodies targeting CD20.
Mosunetuzumab is a CD20xCD3 T-cell engaging bispecific antibody in development for the treatment of people with B-cell non-Hodgkin’s lymphoma (NHL), including follicular lymphoma (FL)1 and diffuse large B-cell lymphoma (DLBCL). In June 2020, mosunetuzumab was granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed/refractory (R/R) FL who have received at least two prior systemic therapies.
Genentech plans to complete a Biologics License Application (BLA) submission to the FDA in the near future for approval consideration from the GO29781 study investigating mosunetuzumab in patients with R/R FL. If approved, mosunetuzumab has the potential to be a first-in-class CD20xCD3 T-cell engaging bispecific antibody in NHL. Roche recently submitted the initial marketing authorization application for mosunetuzumab to the European Medicines Agency (EMA), with the hope to bring this drug as soon as possible to people with NHL. In addition, mosunetuzumab recently began a Phase 1b trial in patients with systemic lupus erythematosus2.
As a part of the option exercise, Biogen will pay a $30 million one-time option fee to Genentech and will pay for a portion of the mosunetuzumab development expenses incurred during 2021. Biogen will have joint decision-making rights related to development and commercialization of mosunetuzumab and Genentech will continue to lead the strategy and implementation of the program.
Subscribe to:
Posts (Atom)