Regenerative Medicine: Does BioMarin Complete Response Letter Change The Outlook? | Seeking Alpha


BioMarin (BMRN) received a complete response letter or CRL for their hemophilia A gene therapy Valrox last week. As a result, the earliest commercial launch is now in 2023.

Audentes (OTCPK:ALPMF) provided an update on their please 3 neuromuscular ASPIRO clinical trial indicating a third patient treated at the higher dose had passed away. This trial was placed on hold after the second patient died.

Both of these products were expected to be approved in 2020. This is a timely reminder that clinical trials of regenerative medicines are not without risk. The question now is: Do these setbacks provide a read through for the group? These unfortunate announcements are not unusual, nor will they be the last, but the overall sector outlook remains strong.

The rest of this article will provide a recap of the revenues being generated by approved regenerative medicine products and a recap of the pipeline coming into this year. A second article being written will look at the Valrox CRL and consider the possible read through to other late stage hemophilia gene therapies.

Gene Therapy Pipeline

The June 2019 publication, Estimating the Clinical Pipeline of Cell and Gene Therapies and Their Potential Economic Impact of the US Healthcare System provides a useful risk-adjusted summary of projected Gene Therapy or GT and Cell Therapy or CT product launches in the US.

The overall design for their analysis, shown in Figure 1, was based upon quantitative modeling using estimated duration and the likelihood of completion of each phase. Additional detail about their methodology and data sources can be found in the publication.

The Citeline database in mid-2019 had 628 active US clinical trials for GT and CT including 174 phase II and 19 phase III studies. Figure 2 shows predicted cumulative minimum, mean and maximum product launches through 2030. This is followed by Table 1 which breaks out the mean cumulative product launches by disease group, and Table 2 which estimates cumulative patients treated.

BioProcess International Sep 2019 article- In the pipeline: Surge of cell and gene therapies likely in 2020-quoted the Alliance for Regenerative Medicine or ARM belief that over 20 cell and gene therapy filings or approval decisions were anticipated by the end of 2020.

Evercore ISI issued several research reports on GT and CT in 2019. They concluded we have begun the Biotech 4.0 gene therapy era based upon program, platform, collaboration, M&A, and IPO trends. They highlighted this onset with the following pharmaceutical revenue graphic showing the impact from the previous biologic era.

Evercore believes the first wave of GT approvals catalyzed Biopharma M&A activity. Note that both BMN270 and AT132 were identified as projected approvals in 2020.

While these two drugs are now delayed beyond 2020, the overall trend is unchanged. Clinical holds and rejected accelerated approvals represent news that is quickly magnified, but within the BIO survey results of clinical risk assessment summarized below. Neither of these programs have failed. They are delayed but the eventual outcome, especially in the case of Valrox, is far from known. I’ll provide a little more detail on the impact of this decision on other late stage hemophilia products in an article being drafted.

Alliance for Regenerative Medicine or ARM

ARM published a Sector Overview of Gene Therapy in March 2019. They concluded that there were 906 companies globally pursuing regenerative medicines including 400 Gene Therapy & Gene-based Medicine companies. 2018 product approvals for gene therapy included Luxturna, Yescarta and Kymriah. The report concluded there were:

  • 341 Phase I programs including 120 gene therapy or GT and 158 cell therapy or CT trials.
  • 595 Phase II programs including 210 GT and 188 CT trials
  • 92 Phase III programs including 32 GT and 16 CT trials.

The ARM website shows 170 anticipated clinical data or events as of December 2019.

Regenerative Medicine Revenues

We are in the early stages of what will be a multi-decade wave of potentially curative regenerative medicines. We have over a dozen approved medicines commercially launched. Revenues grew from $1 billion in 2017 to $3.8 billion in 2019. These products are ramping, have limited capacity and not yet available in major geographies, suggesting this early success will continue.

An additional 92 Phase III trials, about half of which are GT and CT, will likely yield several approvals in the next 12 months. The FDA is on board issuing multiple guidance documents while modernizing approaches to designing clinical trials to help guide and streamline the process. They anticipate receiving 200 INDs per year beginning in 2020 leading to 10 to 20 approvals by 2025.

Most big pharmaceutical companies have either acquired or signed collaboration agreements with the first wave of regenerative medicine companies. Notable acquirers include Amgen (AMGN), Astellas, Biogen (BIIB), Bristol-Myers (BMY), Gilead (GILD), Novartis (NVS)), and Pfizer. Their acquisitions include Audentes, AveXis, Bamboo, Celgene, Juno, Kite, Nightstar, Spark and Tularik. Significant collaborations have been disclosed by several companies in my tracking group including Cellectis (CLLS), Crispr (CRSP), Denali (DNLI), Homology (FIXX), Intellia (NTLA), Uniqure (QURE), Regenxbio (RGNX), Sangamo (SGMO) and Voyager (VYGR).

The news last week does not change this trajectory but is a good reminder that this is cutting-edge science with significant risk. Most programs entering the clinic will not succeed but those that do will provide hope and relief for those suffering from thousands of diseases.

This article is part of an on-going series on the emerging genomics medicine era of precision medicine which kicked off in 2018 with Genomic Medicine: Catch The Gene Therapy Wave.

Disclosure: I am/we are long BMRN, SGMO, QURE, PFE. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

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